Scholars@Duke
Gregory E. Crawford

Gregory E. Crawford

Wilburt C. Davison Distinguished Professor of Pediatrics
Pediatrics, Medical Genetics
greg.crawford@duke.edu
Box 3382 Med Ctr, Durham, NC 27710
Room 2111 CIEMAS, Durham, NC 27708

Selected Publications

Mechanosensitive genomic enhancers potentiate the cellular response to matrix stiffness.

Journal Article Science · December 11, 2025 Epigenetic control of gene expression and cellular phenotype is influenced by changes in the local microenvironment, yet how mechanical cues precisely influence epigenetic state to regulate transcription remains largely unmapped. In this study, we combined ... Full text Link to item Cite

High-throughput characterization of transcription factors that modulate UV damage formation and repair at single-nucleotide resolution.

Journal Article Res Sq · December 10, 2025 Genomic studies have revealed elevated damage and mutation rates in active transcription factor (TF) binding sites in UV-linked cancers. Previous investigations into the relationship between TF activity and UV DNA damage have primarily focused on select TF ... Full text Link to item Cite

Cross-tissue molecular responses in the liver and blood after toxicant exposures.

Journal Article Res Sq · October 10, 2025 Exposure to toxic substances, particularly early in life, can perturb epigenomic marks linked to disease susceptibility. Human studies of environmental exposures often rely on surrogate tissues such as blood, but toxicant accumulation differs across organs ... Full text Link to item Cite

Toxicogenomic Insights into Environmental Toxicant Exposures: The TaRGET II Resource.

Journal Article Res Sq · August 20, 2025 Environmental exposures to toxic chemicals can profoundly alter the transcriptome and epigenome in both humans and animals, contributing to disease development across the lifespan. To elucidate how early-life exposure to toxicants exerts such persistent ef ... Full text Link to item Cite

Comparative mapping of single-cell transcriptomic landscapes in neurodegenerative diseases.

Journal Article Alzheimers Dement · May 2025 INTRODUCTION: Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Parkinson's disease (PD) represent a spectrum of neurodegenerative diseases (NDDs). Here, we performed the first direct comparison of their transcriptomic landscapes. METHODS: We ... Full text Link to item Cite

Massively parallel assessment of gene regulatory activity at human cortical structure associated variants.

Journal Article bioRxiv · February 13, 2025 Genetic association studies have identified hundreds of largely non-coding loci associated with inter-individual differences in the structure of the human cortex, though the specific genetic variants that impact regulatory activity are unknown. We implemen ... Full text Link to item Cite

Characterization and bioinformatic filtering of ambient gRNAs in single-cell CRISPR screens using CLEANSER.

Journal Article Cell Genom · February 12, 2025 Single-cell RNA sequencing CRISPR (perturb-seq) screens enable high-throughput investigation of the genome, allowing for characterization of thousands of genomic perturbations on gene expression. Ambient gRNAs, which are contaminating gRNAs, are a major so ... Full text Link to item Cite

Promoter Deletion Leading to Allele Specific Expression in a Genetically Unsolved Case of Primary Ciliary Dyskinesia.

Journal Article Am J Med Genet A · February 2025 Variation in the non-coding genome represents an understudied mechanism of disease and it remains challenging to predict if single nucleotide variants, small insertions and deletions, or structural variants in non-coding genomic regions will be detrimental ... Full text Link to item Cite

Chromatin Remodeling in Patient-Derived Colorectal Cancer Models.

Conference Adv Sci (Weinh) · April 2024 Patient-Derived Organoids (PDO) and Xenografts (PDX) are the current gold standards for patient-derived models of cancer (PDMC). Nevertheless, how patient tumor cells evolve in these models and the impact on drug response remains unclear. Herein, the trans ... Full text Link to item Cite

Characterization of enhancer activity in early human neurodevelopment using Massively Parallel Reporter Assay (MPRA) and forebrain organoids.

Journal Article Sci Rep · February 16, 2024 Regulation of gene expression through enhancers is one of the major processes shaping the structure and function of the human brain during development. High-throughput assays have predicted thousands of enhancers involved in neurodevelopment, and confirmin ... Full text Link to item Cite

Epstein-Barr virus induces germinal center light zone chromatin architecture and promotes survival through enhancer looping at the BCL2A1 locus.

Journal Article mBio · January 16, 2024 Epstein-Barr virus has evolved with its human host leading to an intimate relationship where infection of antibody-producing B cells mimics the process by which these cells normally recognize foreign antigens and become activated. Virtually everyone in the ... Full text Link to item Cite

Mechanosensitive genomic enhancers potentiate the cellular response to matrix stiffness.

Journal Article bioRxiv · January 10, 2024 Epigenetic control of cellular transcription and phenotype is influenced by changes in the cellular microenvironment, yet how mechanical cues from these microenvironments precisely influence epigenetic state to regulate transcription remains largely unmapp ... Full text Link to item Cite

Integrative single-nucleus multi-omics analysis prioritizes candidate cis and trans regulatory networks and their target genes in Alzheimer's disease brains.

Journal Article Cell Biosci · October 3, 2023 BACKGROUND: The genetic underpinnings of late-onset Alzheimer's disease (LOAD) are yet to be fully elucidated. Although numerous LOAD-associated loci have been discovered, the causal variants and their target genes remain largely unknown. Since the brain i ... Full text Link to item Cite

Characterization of enhancer activity in early human neurodevelopment using Massively parallel reporter assay (MPRA) and forebrain organoids.

Journal Article bioRxiv · August 14, 2023 Regulation of gene expression through enhancers is one of the major processes shaping the structure and function of the human brain during development. High-throughput assays have predicted thousands of enhancers involved in neurodevelopment, and confirmin ... Full text Link to item Cite

Single cell profiling at the maternal-fetal interface reveals a deficiency of PD-L1+ non-immune cells in human spontaneous preterm labor.

Journal Article Sci Rep · May 16, 2023 The mechanisms that underlie the timing of labor in humans are largely unknown. In most pregnancies, labor is initiated at term (≥ 37 weeks gestation), but in a signifiicant number of women spontaneous labor occurs preterm and is associated with increased ... Full text Link to item Cite

Profiling the quantitative occupancy of myriad transcription factors across conditions by modeling chromatin accessibility data.

Journal Article Genome Res · June 2022 Over a thousand different transcription factors (TFs) bind with varying occupancy across the human genome. Chromatin immunoprecipitation (ChIP) can assay occupancy genome-wide, but only one TF at a time, limiting our ability to comprehensively observe the ... Full text Link to item Cite

Enhancer selection dictates gene expression responses in remote organs during tissue regeneration.

Journal Article Nat Cell Biol · May 2022 Acute trauma stimulates local repair mechanisms but can also impact structures distant from the injury, for example through the activity of circulating factors. To study the responses of remote tissues during tissue regeneration, we profiled transcriptomes ... Full text Link to item Cite

Identification of enhancer regulatory elements that direct epicardial gene expression during zebrafish heart regeneration.

Journal Article Development · February 15, 2022 The epicardium is a mesothelial tissue layer that envelops the heart. Cardiac injury activates dynamic gene expression programs in epicardial tissue, which in zebrafish enables subsequent regeneration through paracrine and vascularizing effects. To identif ... Full text Link to item Cite

Epigenetic basis of oncogenic-Kras-mediated epithelial-cellular proliferation and plasticity.

Journal Article Dev Cell · February 7, 2022 Oncogenic Kras induces a hyper-proliferative state that permits cells to progress to neoplasms in diverse epithelial tissues. Depending on the cell of origin, this also involves lineage transformation. Although a multitude of downstream factors have been i ... Full text Open Access Link to item Cite

Parallel single-nucleus chromatin accessibility and transcriptomic profiling of human late-onset Alzheimer's disease brains

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2021 BACKGROUND: In the post-GWAS era for late-onset Alzheimer's disease (LOAD), the precise disease-causing genes, the specific causal variants, and molecular mechanisms mediating their pathogenic effects remain unknown. Recent studies using single-nucleus (sn ... Full text Cite

Chromatin Remodeling of Colorectal Cancer Liver Metastasis is Mediated by an HGF-PU.1-DPP4 Axis.

Journal Article Adv Sci (Weinh) · October 2021 Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC-related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation ... Full text Open Access Link to item Cite

Sex dependent glial-specific changes in the chromatin accessibility landscape in late-onset Alzheimer's disease brains.

Journal Article Mol Neurodegener · August 24, 2021 BACKGROUND: In the post-GWAS era, there is an unmet need to decode the underpinning genetic etiologies of late-onset Alzheimer's disease (LOAD) and translate the associations to causation. METHODS: We conducted ATAC-seq profiling using NeuN sorted-nuclei f ... Full text Link to item Cite

Targeted long-read sequencing identifies missing disease-causing variation.

Journal Article Am J Hum Genet · August 5, 2021 Despite widespread clinical genetic testing, many individuals with suspected genetic conditions lack a precise diagnosis, limiting their opportunity to take advantage of state-of-the-art treatments. In some cases, testing reveals difficult-to-evaluate stru ... Full text Link to item Cite

Cell-type-specific effects of genetic variation on chromatin accessibility during human neuronal differentiation.

Journal Article Nat Neurosci · July 2021 Common genetic risk for neuropsychiatric disorders is enriched in regulatory elements active during cortical neurogenesis. However, it remains poorly understood as to how these variants influence gene regulation. To model the functional impact of common ge ... Full text Link to item Cite

Integrated chromatin and transcriptomic profiling of patient-derived colon cancer organoids identifies personalized drug targets to overcome oxaliplatin resistance.

Journal Article Genes Dis · March 2021 Colorectal cancer is a leading cause of cancer deaths. Most colorectal cancer patients eventually develop chemoresistance to the current standard-of-care therapies. Here, we used patient-derived colorectal cancer organoids to demonstrate that resistant tum ... Full text Link to item Cite

Correction: Common-variant associations with fragile X syndrome.

Journal Article Mol Psychiatry · December 2020 An amendment to this paper has been published and can be accessed via a link at the top of the paper. ... Full text Link to item Cite

Transcriptome and regulatory maps of decidua-derived stromal cells inform gene discovery in preterm birth.

Journal Article Sci Adv · December 2020 While a genetic component of preterm birth (PTB) has long been recognized and recently mapped by genome-wide association studies (GWASs), the molecular determinants underlying PTB remain elusive. This stems in part from an incomplete availability of functi ... Full text Link to item Cite

Identification and requirements of enhancers that direct gene expression during zebrafish fin regeneration.

Journal Article Development · July 30, 2020 To identify candidate tissue regeneration enhancer elements (TREEs) important for zebrafish fin regeneration, we performed ATAC-seq from bulk tissue or purified fibroblasts of uninjured and regenerating caudal fins. We identified tens of thousands of DNA r ... Full text Link to item Cite

Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation.

Journal Article PLoS Genet · January 2020 Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable ... Full text Link to item Cite

The Lineage Determining Factor GRHL2 Collaborates with FOXA1 to Establish a Targetable Pathway in Endocrine Therapy-Resistant Breast Cancer.

Journal Article Cell Rep · October 22, 2019 Notwithstanding the positive clinical impact of endocrine therapies in estrogen receptor-alpha (ERα)-positive breast cancer, de novo and acquired resistance limits the therapeutic lifespan of existing drugs. Taking the position that resistance is nearly in ... Full text Link to item Cite

Evaluating Chromatin Accessibility Differences Across Multiple Primate Species Using a Joint Modeling Approach.

Journal Article Genome Biol Evol · October 1, 2019 Changes in transcriptional regulation are thought to be a major contributor to the evolution of phenotypic traits, but the contribution of changes in chromatin accessibility to the evolution of gene expression remains almost entirely unknown. To address th ... Full text Link to item Cite

CommonMind Consortium provides transcriptomic and epigenomic data for Schizophrenia and Bipolar Disorder.

Journal Article Sci Data · September 24, 2019 Schizophrenia and bipolar disorder are serious mental illnesses that affect more than 2% of adults. While large-scale genetics studies have identified genomic regions associated with disease risk, less is known about the molecular mechanisms by which risk ... Full text Link to item Cite

Open Chromatin Profiling in Adipose Tissue Marks Genomic Regions with Functional Roles in Cardiometabolic Traits.

Journal Article G3 (Bethesda) · August 8, 2019 Identifying the regulatory mechanisms of genome-wide association study (GWAS) loci affecting adipose tissue has been restricted due to limited characterization of adipose transcriptional regulatory elements. We profiled chromatin accessibility in three fro ... Full text Link to item Cite

Comparative Analyses of Chromatin Landscape in White Adipose Tissue Suggest Humans May Have Less Beigeing Potential than Other Primates.

Journal Article Genome Biol Evol · July 1, 2019 Humans carry a much larger percentage of body fat than other primates. Despite the central role of adipose tissue in metabolism, little is known about the evolution of white adipose tissue in primates. Phenotypic divergence is often caused by genetic diver ... Full text Link to item Cite

Common-variant associations with fragile X syndrome.

Journal Article Mol Psychiatry · March 2019 Fragile X syndrome is rare but a prominent cause of intellectual disability. It is usually caused by a de novo mutation that occurs on multiple haplotypes and thus would not be expected to be detectible using genome-wide association (GWA). We conducted GWA ... Full text Link to item Cite

Biological annotation of genetic loci associated with intelligence in a meta-analysis of 87,740 individuals.

Journal Article Mol Psychiatry · February 2019 Variance in IQ is associated with a wide range of health outcomes, and 1% of the population are affected by intellectual disability. Despite a century of research, the fundamental neural underpinnings of intelligence remain unclear. We integrate results fr ... Full text Link to item Cite

Association of Whole-Genome and NETRIN1 Signaling Pathway–Derived Polygenic Risk Scores for Major Depressive Disorder and White Matter Microstructure in the UK Biobank

Journal Article Biological Psychiatry Cognitive Neuroscience and Neuroimaging · January 1, 2019 Background: Major depressive disorder is a clinically heterogeneous psychiatric disorder with a polygenic architecture. Genome-wide association studies have identified a number of risk-associated variants across the genome and have reported growing evidenc ... Full text Cite

Comprehensive functional genomic resource and integrative model for the human brain.

Journal Article Science · December 14, 2018 Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The Psych ... Full text Link to item Cite

Transcriptome and epigenome landscape of human cortical development modeled in organoids.

Journal Article Science · December 14, 2018 Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 1 ... Full text Link to item Cite

IL-1R signaling promotes STAT3 and NF-κB factor recruitment to distal cis-regulatory elements that regulate Il17a/f transcription.

Journal Article J Biol Chem · October 12, 2018 Interleukin (IL)-1β plays a critical role in IL-6β- and transforming growth factor β (TGFβ)-initiated Th17 differentiation and induction of Th17-mediated autoimmunity. However, the means by which IL-1 regulates various aspects of Th17 development remain po ... Full text Link to item Cite

Human cardiac cis-regulatory elements, their cognate transcription factors, and regulatory DNA sequence variants.

Journal Article Genome Res · October 2018 Cis-regulatory elements (CRE), short DNA sequences through which transcription factors (TFs) exert regulatory control on gene expression, are postulated to be the major sites of causal sequence variation underlying the genetics of complex traits and diseas ... Full text Link to item Cite

Glucocorticoid receptor recruits to enhancers and drives activation by motif-directed binding.

Journal Article Genome Res · September 2018 Glucocorticoids are potent steroid hormones that regulate immunity and metabolism by activating the transcription factor (TF) activity of glucocorticoid receptor (GR). Previous models have proposed that DNA binding motifs and sites of chromatin accessibili ... Full text Link to item Cite

Pre-established Chromatin Interactions Mediate the Genomic Response to Glucocorticoids.

Journal Article Cell Syst · August 22, 2018 The glucocorticoid receptor (GR) is a hormone-inducible transcription factor involved in metabolic and anti-inflammatory gene expression responses. To investigate what controls interactions between GR binding sites and their target genes, we used in situ H ... Full text Link to item Cite

Evaluation of chromatin accessibility in prefrontal cortex of individuals with schizophrenia.

Journal Article Nat Commun · August 7, 2018 Schizophrenia genome-wide association studies have identified >150 regions of the genome associated with disease risk, yet there is little evidence that coding mutations contribute to this disorder. To explore the mechanism of non-coding regulatory element ... Full text Link to item Cite

Does Childhood Trauma Moderate Polygenic Risk for Depression? A Meta-analysis of 5765 Subjects From the Psychiatric Genomics Consortium.

Journal Article Biol Psychiatry · July 15, 2018 BACKGROUND: The heterogeneity of genetic effects on major depressive disorder (MDD) may be partly attributable to moderation of genetic effects by environment, such as exposure to childhood trauma (CT). Indeed, previous findings in two independent cohorts ... Full text Link to item Cite

Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.

Journal Article Nat Genet · May 2018 Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 ... Full text Link to item Cite

Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights.

Journal Article Nat Genet · April 2018 Genome-wide association studies (GWAS) have identified over 100 risk loci for schizophrenia, but the causal mechanisms remain largely unknown. We performed a transcriptome-wide association study (TWAS) integrating a schizophrenia GWAS of 79,845 individuals ... Full text Link to item Cite

Comparative Serum Challenges Show Divergent Patterns of Gene Expression and Open Chromatin in Human and Chimpanzee.

Journal Article Genome Biol Evol · March 1, 2018 Humans experience higher rates of age-associated diseases than our closest living evolutionary relatives, chimpanzees. Environmental factors can explain many of these increases in disease risk, but species-specific genetic changes can also play a role. All ... Full text Open Access Link to item Cite

Tissue- and strain-specific effects of a genotoxic carcinogen 1,3-butadiene on chromatin and transcription.

Journal Article Mamm Genome · February 2018 Epigenetic effects of environmental chemicals are under intense investigation to fill existing knowledge gaps between environmental/occupational exposures and adverse health outcomes. Chromatin accessibility is one prominent mechanism of epigenetic control ... Full text Link to item Cite

Screening Regulatory Element Function with CRISPR/Cas9-based Epigenome Editing.

Journal Article Methods Mol Biol · 2018 Genomic regulatory elements that control gene expression play an important role in many traits and diseases. Identifying the regulatory elements associated with each gene or phenotype and understanding the function of that element remain a significant chal ... Full text Link to item Cite

Genome-wide interaction study of a proxy for stress-sensitivity and its prediction of major depressive disorder.

Journal Article PLoS One · 2018 Individual response to stress is correlated with neuroticism and is an important predictor of both neuroticism and the onset of major depressive disorder (MDD). Identification of the genetics underpinning individual differences in response to negative even ... Full text Link to item Cite

Genetic Association of Major Depression With Atypical Features and Obesity-Related Immunometabolic Dysregulations.

Journal Article JAMA Psychiatry · December 1, 2017 IMPORTANCE: The association between major depressive disorder (MDD) and obesity may stem from shared immunometabolic mechanisms particularly evident in MDD with atypical features, characterized by increased appetite and/or weight (A/W) during an active epi ... Full text Link to item Cite

Incomplete MyoD-induced transdifferentiation is associated with chromatin remodeling deficiencies.

Journal Article Nucleic Acids Res · November 16, 2017 Our current understanding of cellular transdifferentiation systems is limited. It is oftentimes unknown, at a genome-wide scale, how much transdifferentiated cells differ quantitatively from both the starting cells and the target cells. Focusing on transdi ... Full text Link to item Cite

Variation in DNA-Damage Responses to an Inhalational Carcinogen (1,3-Butadiene) in Relation to Strain-Specific Differences in Chromatin Accessibility and Gene Transcription Profiles in C57BL/6J and CAST/EiJ Mice.

Journal Article Environ Health Perspect · October 16, 2017 BACKGROUND: The damaging effects of exposure to environmental toxicants differentially affect genetically distinct individuals, but the mechanisms contributing to these differences are poorly understood. Genetic variation affects the establishment of the g ... Full text Link to item Cite

Genetic and epigenetic determinants of inter-individual variability in responses to toxicants.

Journal Article Curr Opin Toxicol · October 2017 It is well established that genetic variability has a major impact on susceptibility to common diseases, responses to drugs and toxicants, and influences disease-related outcomes. The appreciation that epigenetic marks also vary across the population is gr ... Full text Link to item Cite

Microbiota regulate intestinal epithelial gene expression by suppressing the transcription factor Hepatocyte nuclear factor 4 alpha.

Journal Article Genome Res · July 2017 Microbiota influence diverse aspects of intestinal physiology and disease in part by controlling tissue-specific transcription of host genes. However, host genomic mechanisms mediating microbial control of intestinal gene expression are poorly understood. ... Full text Link to item Cite

CRISPR-Cas9 epigenome editing enables high-throughput screening for functional regulatory elements in the human genome.

Journal Article Nat Biotechnol · June 2017 Large genome-mapping consortia and thousands of genome-wide association studies have identified non-protein-coding elements in the genome as having a central role in various biological processes. However, decoding the functions of the millions of putative ... Full text Link to item Cite

Reducing mitochondrial reads in ATAC-seq using CRISPR/Cas9.

Journal Article Sci Rep · May 26, 2017 ATAC-seq is a high-throughput sequencing technique that identifies open chromatin. Depending on the cell type, ATAC-seq samples may contain ~20-80% of mitochondrial sequencing reads. As the regions of open chromatin of interest are usually located in the n ... Full text Link to item Cite

Genome-wide identification of regulatory elements in Sertoli cells.

Journal Article Development · February 15, 2017 A current goal of molecular biology is to identify transcriptional networks that regulate cell differentiation. However, identifying functional gene regulatory elements has been challenging in the context of developing tissues where material is limited and ... Full text Link to item Cite

Stringent comparative sequence analysis reveals SOX10 as a putative inhibitor of glial cell differentiation.

Journal Article BMC Genomics · November 7, 2016 BACKGROUND: The transcription factor SOX10 is essential for all stages of Schwann cell development including myelination. SOX10 cooperates with other transcription factors to activate the expression of key myelin genes in Schwann cells and is therefore a c ... Full text Link to item Cite

Direct GR Binding Sites Potentiate Clusters of TF Binding across the Human Genome.

Journal Article Cell · August 25, 2016 The glucocorticoid receptor (GR) binds the human genome at >10,000 sites but only regulates the expression of hundreds of genes. To determine the functional effect of each site, we measured the glucocorticoid (GC) responsive activity of nearly all GR bindi ... Full text Link to item Cite

The genetic regulatory signature of type 2 diabetes in human skeletal muscle.

Journal Article Nat Commun · June 29, 2016 Type 2 diabetes (T2D) results from the combined effects of genetic and environmental factors on multiple tissues over time. Of the >100 variants associated with T2D and related traits in genome-wide association studies (GWAS), >90% occur in non-coding regi ... Full text Link to item Cite

Differential contribution of cis-regulatory elements to higher order chromatin structure and expression of the CFTR locus.

Journal Article Nucleic Acids Res · April 20, 2016 Higher order chromatin structure establishes domains that organize the genome and coordinate gene expression. However, the molecular mechanisms controlling transcription of individual loci within a topological domain (TAD) are not fully understood. The cys ... Full text Link to item Cite

Mapping nucleosome positions using DNase-seq.

Journal Article Genome Res · March 2016 Although deoxyribonuclease I (DNase I) was used to probe the structure of the nucleosome in the 1960s and 1970s, in the current high-throughput sequencing era, DNase I has mainly been used to study genomic regions devoid of nucleosomes. Here, we reveal for ... Full text Link to item Cite

HDAC inhibitors cause site-specific chromatin remodeling at PU.1-bound enhancers in K562 cells.

Journal Article Epigenetics Chromatin · 2016 BACKGROUND: Small molecule inhibitors of histone deacetylases (HDACi) hold promise as anticancer agents for particular malignancies. However, clinical use is often confounded by toxicity, perhaps due to indiscriminate hyperacetylation of cellular proteins. ... Full text Open Access Link to item Cite

Highly specific epigenome editing by CRISPR-Cas9 repressors for silencing of distal regulatory elements.

Journal Article Nat Methods · December 2015 Epigenome editing with the CRISPR (clustered, regularly interspaced, short palindromic repeats)-Cas9 platform is a promising technology for modulating gene expression to direct cell phenotype and to dissect the causal epigenetic mechanisms of gene regulati ... Full text Link to item Cite

The PsychENCODE project.

Journal Article Nat Neurosci · December 2015 Recent research on disparate psychiatric disorders has implicated rare variants in genes involved in global gene regulation and chromatin modification, as well as many common variants located primarily in regulatory regions of the genome. Understanding pre ... Full text Open Access Link to item Cite

Genetic variants and cellular stressors associated with exfoliation syndrome modulate promoter activity of a lncRNA within the LOXL1 locus.

Journal Article Hum Mol Genet · November 15, 2015 Exfoliation syndrome (XFS) is a common, age-related, systemic fibrillinopathy. It greatly increases risk of exfoliation glaucoma (XFG), a major worldwide cause of irreversible blindness. Coding variants in the lysyl oxidase-like 1 (LOXL1) gene are strongly ... Full text Link to item Cite

Genomic analysis reveals distinct mechanisms and functional classes of SOX10-regulated genes in melanocytes.

Journal Article Hum Mol Genet · October 1, 2015 SOX10 is required for melanocyte development and maintenance, and has been linked to melanoma initiation and progression. However, the molecular mechanisms by which SOX10 guides the appropriate gene expression programs necessary to promote the melanocyte l ... Full text Link to item Cite

Genome-wide specificity of DNA binding, gene regulation, and chromatin remodeling by TALE- and CRISPR/Cas9-based transcriptional activators.

Journal Article Genome Res · August 2015 Genome engineering technologies based on the CRISPR/Cas9 and TALE systems are enabling new approaches in science and biotechnology. However, the specificity of these tools in complex genomes and the role of chromatin structure in determining DNA binding ar ... Full text Link to item Cite

Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers.

Journal Article Nat Biotechnol · May 2015 Technologies that enable targeted manipulation of epigenetic marks could be used to precisely control cell phenotype or interrogate the relationship between the epigenome and transcriptional control. Here we describe a programmable, CRISPR-Cas9-based acety ... Full text Link to item Cite

Regulation of chromatin accessibility and Zic binding at enhancers in the developing cerebellum.

Journal Article Nat Neurosci · May 2015 To identify chromatin mechanisms of neuronal differentiation, we characterized chromatin accessibility and gene expression in cerebellar granule neurons (CGNs) of the developing mouse. We used DNase-seq to map accessibility of cis-regulatory elements and R ... Full text Link to item Cite

Evolution of gene expression network underlying a disease state

Conference INTEGRATIVE AND COMPARATIVE BIOLOGY · April 1, 2015 Link to item Cite

Ascl1 Coordinately Regulates Gene Expression and the Chromatin Landscape during Neurogenesis.

Journal Article Cell Rep · March 10, 2015 The proneural transcription factor Ascl1 coordinates gene expression in both proliferating and differentiating progenitors along the neuronal lineage. Here, we used a cellular model of neurogenesis to investigate how Ascl1 interacts with the chromatin land ... Full text Link to item Cite

Genome accessibility is widely preserved and locally modulated during mitosis.

Journal Article Genome Res · February 2015 Mitosis entails global alterations to chromosome structure and nuclear architecture, concomitant with transient silencing of transcription. How cells transmit transcriptional states through mitosis remains incompletely understood. While many nuclear factor ... Full text Link to item Cite

Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multifunctional regulator of self-renewal.

Journal Article Genome Res · January 2015 The gene regulatory network (GRN) that supports neural stem cell (NS cell) self-renewal has so far been poorly characterized. Knowledge of the central transcription factors (TFs), the noncoding gene regulatory regions that they bind to, and the genes whose ... Full text Link to item Cite

Interactions of chromatin context, binding site sequence content, and sequence evolution in stress-induced p53 occupancy and transactivation.

Journal Article PLoS Genet · January 2015 Cellular stresses activate the tumor suppressor p53 protein leading to selective binding to DNA response elements (REs) and gene transactivation from a large pool of potential p53 REs (p53REs). To elucidate how p53RE sequences and local chromatin context i ... Full text Open Access Link to item Cite

Open chromatin mapping identifies transcriptional networks regulating human epididymis epithelial function.

Journal Article Mol Hum Reprod · December 2014 The epithelium lining the epididymis in the male reproductive tract maintains a luminal environment that promotes sperm cell maturation. This process is dependent on the coordinated expression of many genes that encode proteins with a role in epithelial tr ... Full text Link to item Cite

Quantitative genetics of CTCF binding reveal local sequence effects and different modes of X-chromosome association.

Journal Article PLoS Genet · November 2014 Associating genetic variation with quantitative measures of gene regulation offers a way to bridge the gap between genotype and complex phenotypes. In order to identify quantitative trait loci (QTLs) that influence the binding of a transcription factor in ... Full text Open Access Link to item Cite

Explicit DNase sequence bias modeling enables high-resolution transcription factor footprint detection.

Journal Article Nucleic Acids Res · October 29, 2014 DNaseI footprinting is an established assay for identifying transcription factor (TF)-DNA interactions with single base pair resolution. High-throughput DNase-seq assays have recently been used to detect in vivo DNase footprints across the genome. Multiple ... Full text Open Access Link to item Cite

VEGF changes chromatin landscape in endothelial cell

Journal Article ANGIOGENESIS · October 1, 2014 Link to item Cite

Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape.

Journal Article Genome Res · September 2014 Microbiota regulate intestinal physiology by modifying host gene expression along the length of the intestine, but the underlying regulatory mechanisms remain unresolved. Transcriptional specificity occurs through interactions between transcription factors ... Full text Link to item Cite

Epigenomic comparison reveals activation of "seed" enhancers during transition from naive to primed pluripotency.

Journal Article Cell Stem Cell · June 5, 2014 Naive mouse embryonic stem cells (mESCs) and primed epiblast stem cells (mEpiSCs) represent successive snapshots of pluripotency during embryogenesis. Using transcriptomic and epigenomic mapping we show that a small fraction of transcripts are differential ... Full text Link to item Cite

Notch signaling genes: myogenic DNA hypomethylation and 5-hydroxymethylcytosine.

Journal Article Epigenetics · June 2014 Notch intercellular signaling is critical for diverse developmental pathways and for homeostasis in various types of stem cells and progenitor cells. Because Notch gene products need to be precisely regulated spatially and temporally, epigenetics is likely ... Full text Link to item Cite

Defining functional DNA elements in the human genome.

Journal Article Proc Natl Acad Sci U S A · April 29, 2014 With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribut ... Full text Link to item Cite

Deletion of a conserved cis-element in the Ifng locus highlights the role of acute histone acetylation in modulating inducible gene transcription.

Journal Article PLoS Genet · January 2014 Differentiation-dependent regulation of the Ifng cytokine gene locus in T helper (Th) cells has emerged as an excellent model for functional study of distal elements that control lineage-specific gene expression. We previously identified a cis-regulatory e ... Full text Link to item Cite

Deletion of a Conserved cis-Element in the Ifng Locus Highlights the Role of Acute Histone Acetylation in Modulating Inducible Gene Transcription

Journal Article Plos Genetics · January 1, 2014 Differentiation-dependent regulation of the Ifng cytokine gene locus in T helper (Th) cells has emerged as an excellent model for functional study of distal elements that control lineage-specific gene expression. We previously identified a cis-regulatory e ... Full text Cite

Chromatin accessibility mapping identifies mediators of basal transcription and retinoid-induced repression of OTX2 in medulloblastoma.

Journal Article PLoS One · 2014 Despite an emerging understanding of the genetic alterations giving rise to various tumors, the mechanisms whereby most oncogenes are overexpressed remain unclear. Here we have utilized an integrated approach of genomewide regulatory element mapping via DN ... Full text Open Access Link to item Cite

Distinct properties of cell-type-specific and shared transcription factor binding sites.

Journal Article Mol Cell · October 10, 2013 Most human transcription factors bind a small subset of potential genomic sites and often use different subsets in different cell types. To identify mechanisms that govern cell-type-specific transcription factor binding, we used an integrative approach to ... Full text Link to item Cite

A genome-wide analysis of open chromatin in human epididymis epithelial cells reveals candidate regulatory elements for genes coordinating epididymal function.

Journal Article Biol Reprod · October 2013 The epithelium lining the epididymis has a pivotal role in ensuring a luminal environment that can support normal sperm maturation. Many of the individual genes that encode proteins involved in establishing the epididymal luminal fluid are well characteriz ... Full text Link to item Cite

RNA-guided gene activation by CRISPR-Cas9-based transcription factors.

Journal Article Nat Methods · October 2013 Technologies for engineering synthetic transcription factors have enabled many advances in medical and scientific research. In contrast to existing methods based on engineering of DNA-binding proteins, we created a Cas9-based transactivator that is targete ... Full text Link to item Cite

DNA methylation and differentiation: HOX genes in muscle cells.

Journal Article Epigenetics Chromatin · August 2, 2013 BACKGROUND: Tight regulation of homeobox genes is essential for vertebrate development. In a study of genome-wide differential methylation, we recently found that homeobox genes, including those in the HOX gene clusters, were highly overrepresented among t ... Full text Link to item Cite

DNase-seq predicts regions of rotational nucleosome stability across diverse human cell types.

Journal Article Genome Res · July 2013 DNase-seq is primarily used to identify nucleosome-depleted DNase I hypersensitive (DHS) sites genome-wide that correspond to active regulatory elements. However, ≈ 40 yr ago it was demonstrated that DNase I also digests with a ≈ 10-bp periodicity around n ... Full text Link to item Cite

A dynamic H3K27ac signature identifies VEGFA-stimulated endothelial enhancers and requires EP300 activity.

Journal Article Genome Res · June 2013 Histone modifications are now well-established mediators of transcriptional programs that distinguish cell states. However, the kinetics of histone modification and their role in mediating rapid, signal-responsive gene expression changes has been little st ... Full text Link to item Cite

Patterns of regulatory activity across diverse human cell types predict tissue identity, transcription factor binding, and long-range interactions.

Journal Article Genome Res · May 2013 Regulatory elements recruit transcription factors that modulate gene expression distinctly across cell types, but the relationships among these remains elusive. To address this, we analyzed matched DNase-seq and gene expression data for 112 human samples r ... Full text Link to item Cite

Synergistic and tunable human gene activation by combinations of synthetic transcription factors.

Journal Article Nat Methods · March 2013 Mammalian genes are regulated by the cooperative and synergistic actions of many transcription factors. In this study we recapitulate this complex regulation in human cells by targeting endogenous gene promoters, including regions of closed chromatin upstr ... Full text Link to item Cite

Early de novo DNA methylation and prolonged demethylation in the muscle lineage.

Journal Article Epigenetics · March 2013 Myogenic cell cultures derived from muscle biopsies are excellent models for human cell differentiation. We report the first comprehensive analysis of myogenesis-specific DNA hyper- and hypo-methylation throughout the genome for human muscle progenitor cel ... Full text Link to item Cite

Dynamic DNA methylation across diverse human cell lines and tissues.

Journal Article Genome Res · March 2013 As studies of DNA methylation increase in scope, it has become evident that methylation has a complex relationship with gene expression, plays an important role in defining cell types, and is disrupted in many diseases. We describe large-scale single-base ... Full text Link to item Cite

RNA-guided gene activation by CRISPR-Cas9-based transcription factors

Journal Article Nature Methods · 2013 Technologies for engineering synthetic transcription factors have enabled many advances in medical and scientific research. In contrast to existing methods based on engineering of DNA-binding proteins, we created a Cas9-based transactivator that is targete ... Full text Cite

Site-specific silencing of regulatory elements as a mechanism of X inactivation.

Journal Article Cell · November 21, 2012 The inactive X chromosome's (Xi) physical territory is microscopically devoid of transcriptional hallmarks and enriched in silencing-associated modifications. How these microscopic signatures relate to specific Xi sequences is unknown. Therefore, we profil ... Full text Link to item Cite

Chromatin accessibility reveals insights into androgen receptor activation and transcriptional specificity.

Journal Article Genome Biol · October 3, 2012 BACKGROUND: Epigenetic mechanisms such as chromatin accessibility impact transcription factor binding to DNA and transcriptional specificity. The androgen receptor (AR), a master regulator of the male phenotype and prostate cancer pathogenesis, acts primar ... Full text Link to item Cite

The accessible chromatin landscape of the human genome.

Journal Article Nature · September 6, 2012 DNase I hypersensitive sites (DHSs) are markers of regulatory DNA and have underpinned the discovery of all classes of cis-regulatory elements including enhancers, promoters, insulators, silencers and locus control regions. Here we present the first extens ... Full text Link to item Cite

An integrated encyclopedia of DNA elements in the human genome.

Journal Article Nature · September 6, 2012 The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor a ... Full text Link to item Cite

The hypersensitive glucocorticoid response specifically regulates period 1 and expression of circadian genes.

Journal Article Mol Cell Biol · September 2012 Glucocorticoids regulate gene expression by binding and activating the glucocorticoid receptor (GR). While ligand affinity determines the global sensitivity of the response, additional proteins act on the genome to tune sensitivity of some genes. However, ... Full text Link to item Cite

Predicting cell-type-specific gene expression from regions of open chromatin.

Journal Article Genome Res · September 2012 Complex patterns of cell-type-specific gene expression are thought to be achieved by combinatorial binding of transcription factors (TFs) to sequence elements in regulatory regions. Predicting cell-type-specific expression in mammals has been hindered by t ... Full text Link to item Cite

An encyclopedia of mouse DNA elements (Mouse ENCODE).

Journal Article Genome Biol · August 13, 2012 To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome. ... Full text Link to item Cite

An encyclopedia of mouse DNA elements (Mouse ENCODE)

Journal Article Genome Biology · August 13, 2012 To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome. ... Full text Cite

Extensive evolutionary changes in regulatory element activity during human origins are associated with altered gene expression and positive selection.

Journal Article PLoS Genet · June 2012 Featured Publication Understanding the molecular basis for phenotypic differences between humans and other primates remains an outstanding challenge. Mutations in non-coding regulatory DNA that alter gene expression have been hypothesized as a key driver of these phenotypic di ... Full text Link to item Cite

H3K4me3 inversely correlates with DNA methylation at a large class of non-CpG-island-containing start sites.

Journal Article Genome Med · May 28, 2012 Featured Publication BACKGROUND: In addition to mutations, epigenetic silencing of genes has been recognized as a fundamental mechanism that promotes human carcinogenesis. To date, characterization of epigenetic gene silencing has largely focused on genes in which silencing is ... Full text Link to item Cite

Effects of sequence variation on differential allelic transcription factor occupancy and gene expression.

Journal Article Genome Res · May 2012 Featured Publication A complex interplay between transcription factors (TFs) and the genome regulates transcription. However, connecting variation in genome sequence with variation in TF binding and gene expression is challenging due to environmental differences between indivi ... Full text Link to item Cite

A genome-wide analysis of open chromatin in human tracheal epithelial cells reveals novel candidate regulatory elements for lung function.

Journal Article Thorax · May 2012 Featured Publication BACKGROUND: Distal cell-type-specific regulatory elements may be located at very large distances from the genes that they control and are often hidden within intergenic regions or in introns of other genes. The development of methods that enable mapping of ... Full text Link to item Cite

Abstract 2923: Androgen receptor activation changes chromatin structure and transcriptional activation

Journal Article Cancer Research · April 15, 2012 AbstractEpigenetic mechanisms such as chromatin accessibility and histone modifications impact transcription factor binding to DNA and transcriptional specificity. The androgen receptor (AR), a master regula ... Full text Cite

DNase I sensitivity QTLs are a major determinant of human expression variation.

Journal Article Nature · February 5, 2012 Featured Publication The mapping of expression quantitative trait loci (eQTLs) has emerged as an important tool for linking genetic variation to changes in gene regulation. However, it remains difficult to identify the causal variants underlying eQTLs, and little is known abou ... Full text Link to item Cite

Dissecting the regulatory architecture of gene expression QTLs.

Journal Article Genome Biol · January 31, 2012 Featured Publication BACKGROUND: Expression quantitative trait loci (eQTLs) are likely to play an important role in the genetics of complex traits; however, their functional basis remains poorly understood. Using the HapMap lymphoblastoid cell lines, we combine 1000 Genomes ge ... Full text Link to item Cite

Cell-type specific and combinatorial usage of diverse transcription factors revealed by genome-wide binding studies in multiple human cells.

Journal Article Genome Res · January 2012 Featured Publication Cell-type diversity is governed in part by differential gene expression programs mediated by transcription factor (TF) binding. However, there are few systematic studies of the genomic binding of different types of TFs across a wide range of human cell typ ... Full text Link to item Cite

High-resolution mapping of open chromatin in the rice genome.

Journal Article Genome Res · January 2012 Featured Publication Gene expression is controlled by the complex interaction of transcription factors binding to promoters and other regulatory DNA elements. One common characteristic of the genomic regions associated with regulatory proteins is a pronounced sensitivity to DN ... Full text Link to item Cite

Mutational signatures of de-differentiation in functional non-coding regions of melanoma genomes.

Journal Article PLoS Genet · 2012 Much emphasis has been placed on the identification, functional characterization, and therapeutic potential of somatic variants in tumor genomes. However, the majority of somatic variants lie outside coding regions and their role in cancer progression rema ... Full text Link to item Cite

Dynamics of the epigenetic landscape during erythroid differentiation after GATA1 restoration.

Journal Article Genome Res · October 2011 Featured Publication Interplays among lineage-specific nuclear proteins, chromatin modifying enzymes, and the basal transcription machinery govern cellular differentiation, but their dynamics of action and coordination with transcriptional control are not fully understood. Alt ... Full text Link to item Cite

Open chromatin defined by DNaseI and FAIRE identifies regulatory elements that shape cell-type identity.

Journal Article Genome Res · October 2011 Featured Publication The human body contains thousands of unique cell types, each with specialized functions. Cell identity is governed in large part by gene transcription programs, which are determined by regulatory elements encoded in DNA. To identify regulatory elements act ... Full text Link to item Cite

Gene expression during normal and FSHD myogenesis.

Journal Article BMC Med Genomics · September 27, 2011 Featured Publication BACKGROUND: Facioscapulohumeral muscular dystrophy (FSHD) is a dominant disease linked to contraction of an array of tandem 3.3-kb repeats (D4Z4) at 4q35. Within each repeat unit is a gene, DUX4, that can encode a protein containing two homeodomains. A DUX ... Full text Link to item Cite

FINDING TARGETS FOR FSH DYSTROPHY THERAPY

Conference JOURNAL OF GENE MEDICINE · July 1, 2011 Link to item Cite

A user's guide to the encyclopedia of DNA elements (ENCODE).

Journal Article PLoS Biol · April 2011 The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating mu ... Full text Link to item Cite

High-resolution genome-wide in vivo footprinting of diverse transcription factors in human cells.

Journal Article Genome Res · March 2011 Featured Publication Regulation of gene transcription in diverse cell types is determined largely by varied sets of cis-elements where transcription factors bind. Here we demonstrate that data from a single high-throughput DNase I hypersensitivity assay can delineate hundreds ... Full text Link to item Cite

Global epigenomic analysis of primary human pancreatic islets provides insights into type 2 diabetes susceptibility loci.

Journal Article Cell Metab · November 3, 2010 Featured Publication Identifying cis-regulatory elements is important to understanding how human pancreatic islets modulate gene expression in physiologic or pathophysiologic (e.g., diabetic) conditions. We conducted genome-wide analysis of DNase I hypersensitive sites, histon ... Full text Link to item Cite

Allele-specific and heritable chromatin signatures in humans.

Journal Article Hum Mol Genet · October 15, 2010 Featured Publication Next-generation sequencing-based assays to detect gene regulatory elements are enabling the analysis of individual-to-individual and allele-specific variation of chromatin status and transcription factor binding in humans. Recently, a number of studies hav ... Full text Link to item Cite

Modular utilization of distal cis-regulatory elements controls Ifng gene expression in T cells activated by distinct stimuli.

Journal Article Immunity · July 23, 2010 Featured Publication Distal cis-regulatory elements play essential roles in the T lineage-specific expression of cytokine genes. We have mapped interactions of three trans-acting factors-NF-kappaB, STAT4, and T-bet-with cis elements in the Ifng locus. We find that RelA is crit ... Full text Link to item Cite

CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression.

Journal Article PLoS Genet · July 15, 2010 Featured Publication CHD7 is one of nine members of the chromodomain helicase DNA-binding domain family of ATP-dependent chromatin remodeling enzymes found in mammalian cells. De novo mutation of CHD7 is a major cause of CHARGE syndrome, a genetic condition characterized by mu ... Full text Open Access Link to item Cite

CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression.

Journal Article PLoS genetics · July 1, 2010 CHD7 is one of nine members of the chromodomain helicase DNA-binding domain family of ATP-dependent chromatin remodeling enzymes found in mammalian cells. De novo mutation of CHD7 is a major cause of CHARGE syndrome, a genetic condition characterized by mu ... Cite

Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage.

Journal Article Immunity · May 28, 2010 Featured Publication Phenotypic plasticity of T helper 17 (Th17) cells suggests instability of chromatin structure of key genes of this lineage. We identified epigenetic modifications across the clustered Il17a and Il17f and the Ifng loci before and after differential IL-12 or ... Full text Link to item Cite

Heritable individual-specific and allele-specific chromatin signatures in humans.

Journal Article Science · April 9, 2010 Featured Publication The extent to which variation in chromatin structure and transcription factor binding may influence gene expression, and thus underlie or contribute to variation in phenotype, is unknown. To address this question, we cataloged both individual-to-individual ... Full text Link to item Cite

DNaseI hypersensitivity at gene-poor, FSH dystrophy-linked 4q35.2.

Journal Article Nucleic Acids Res · December 2009 Featured Publication A subtelomeric region, 4q35.2, is implicated in facioscapulohumeral muscular dystrophy (FSHD), a dominant disease thought to involve local pathogenic changes in chromatin. FSHD patients have too few copies of a tandem 3.3-kb repeat (D4Z4) at 4q35.2. No phe ... Full text Link to item Cite

Intronic enhancers coordinate epithelial-specific looping of the active CFTR locus.

Journal Article Proc Natl Acad Sci U S A · November 24, 2009 Featured Publication The regulated expression of large human genes can depend on long-range interactions to establish appropriate three-dimensional structures across the locus. The cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encompasses 189 kb of gen ... Full text Link to item Cite

Histone modifications at human enhancers reflect global cell-type-specific gene expression.

Journal Article Nature · May 7, 2009 Featured Publication The human body is composed of diverse cell types with distinct functions. Although it is known that lineage specification depends on cell-specific gene expression, which in turn is driven by promoters, enhancers, insulators and other cis-regulatory DNA seq ... Full text Link to item Cite

A complex intronic enhancer regulates expression of the CFTR gene by direct interaction with the promoter.

Journal Article J Cell Mol Med · April 2009 Featured Publication Genes can maintain spatiotemporal expression patterns by long-range interactions between cis-acting elements. The cystic fibrosis transmembrane conductance regulator gene (CFTR) is expressed primarily in epithelial cells. An element located within a DNase ... Full text Open Access Link to item Cite

Discovering sequences with potential regulatory characteristics.

Journal Article Genomics · April 2009 Featured Publication We developed a computational model to explore the hypothesis that regulatory instructions are context dependent and conveyed through specific 'codes' in human genomic DNA. We provide examples of correlation of computational predictions to reported mapped D ... Full text Link to item Cite

Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns.

Journal Article Genome Res · April 2009 Featured Publication CHD7 is a member of the chromodomain helicase DNA binding domain family of ATP-dependent chromatin remodeling enzymes. De novo mutation of the CHD7 gene is a major cause of CHARGE syndrome, a genetic disease characterized by a complex constellation of birt ... Full text Link to item Cite

Mapping regulatory elements by DNaseI hypersensitivity chip (DNase-Chip).

Journal Article Methods Mol Biol · 2009 Featured Publication Historically, the simplest method to robustly identify active gene regulatory elements has been enzymatic digestion of nuclear DNA by nucleases such as DNaseI. Regions of extreme chromatin accessibility to DNaseI, commonly known as DNaseI hypersensitive si ... Full text Link to item Cite

F-Seq: a feature density estimator for high-throughput sequence tags.

Journal Article Bioinformatics · November 1, 2008 Featured Publication UNLABELLED: Tag sequencing using high-throughput sequencing technologies are now regularly employed to identify specific sequence features, such as transcription factor binding sites (ChIP-seq) or regions of open chromatin (DNase-seq). To intuitively summa ... Full text Link to item Cite

High-resolution mapping and characterization of open chromatin across the genome.

Journal Article Cell · January 25, 2008 Featured Publication Mapping DNase I hypersensitive (HS) sites is an accurate method of identifying the location of genetic regulatory elements, including promoters, enhancers, silencers, insulators, and locus control regions. We employed high-throughput sequencing and whole-g ... Full text Link to item Cite

Interferon regulatory factors are transcriptional regulators of adipogenesis.

Journal Article Cell Metab · January 2008 Featured Publication We have sought to identify transcriptional pathways in adipogenesis using an integrated experimental and computational approach. Here, we employ high-throughput DNase hypersensitivity analysis to find regions of altered chromatin structure surrounding key ... Full text Link to item Cite

Identification and characterization of cell type-specific and ubiquitous chromatin regulatory structures in the human genome.

Journal Article PLoS Genet · August 2007 Featured Publication The identification of regulatory elements from different cell types is necessary for understanding the mechanisms controlling cell type-specific and housekeeping gene expression. Mapping DNaseI hypersensitive (HS) sites is an accurate method for identifyin ... Full text Link to item Cite

Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project.

Journal Article Nature · June 14, 2007 Featured Publication We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number o ... Full text Link to item Cite

Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome.

Journal Article Nat Genet · March 2007 Featured Publication Eukaryotic gene transcription is accompanied by acetylation and methylation of nucleosomes near promoters, but the locations and roles of histone modifications elsewhere in the genome remain unclear. We determined the chromatin modification states in high ... Full text Link to item Cite

Activation of TLX3 and NKX2-5 in t(5;14)(q35;q32) T-cell acute lymphoblastic leukemia by remote 3'-BCL11B enhancers and coregulation by PU.1 and HMGA1.

Journal Article Cancer Res · February 15, 2007 Featured Publication In T-cell acute lymphoblastic leukemia, alternative t(5;14)(q35;q32.2) forms effect dysregulation of either TLX3 or NKX2-5 homeobox genes at 5q35 by juxtaposition with 14q32.2 breakpoints dispersed across the BCL11B downstream genomic desert. Leukemic gene ... Full text Link to item Cite

Identification and characterization of cell type-specific and ubiquitous chromatin regulatory structures in the human genome.

Journal Article PLoS genetics · 2007 The identification of regulatory elements from different cell types is necessary for understanding the mechanisms controlling cell type-specific and housekeeping gene expression. Mapping DNaseI hypersensitive (HS) sites is an accurate method for identifyin ... Full text Cite

Inhibition of TLX3 and NKX2-5 in t(5;14)(q35;q32) T-ALL after Blocking Remote 3′-BCL11B Enhancer Sequences with Matching DNA Oligos Reveals Coregulation by PU.1 and HMGA1.

Conference Blood · November 1, 2006 AbstractIn T-cell acute lymphoblastic leukaemia (T-ALL) alternative t(5;14)(q35;q32.2) forms effect leukemic dysregulation of either TLX3 or NKX2-5 homeobox genes at 5q35 by juxtaposition with 3′-BCL11B at 1 ... Full text Cite

DNase-chip: a high-resolution method to identify DNase I hypersensitive sites using tiled microarrays.

Journal Article Nat Methods · July 2006 Featured Publication Mapping DNase I hypersensitive sites is an accurate method of identifying the location of gene regulatory elements, including promoters, enhancers, silencers and locus control regions. Although Southern blots are the traditional method of identifying DNase ... Full text Link to item Cite

Distant conserved sequences flanking endothelial-specific promoters contain tissue-specific DNase-hypersensitive sites and over-represented motifs.

Journal Article Hum Mol Genet · July 1, 2006 Featured Publication The transcriptional regulation of genes is a complex process, particularly for genes exhibiting a tissue-specific pattern of expression. We studied 28 genes that are expressed primarily in endothelial cells, another 28 genes that are expressed highly, but ... Full text Link to item Cite

Retroviral DNA integration: viral and cellular determinants of target-site selection.

Journal Article PLoS Pathog · June 2006 Featured Publication Retroviruses differ in their preferences for sites for viral DNA integration in the chromosomes of infected cells. Human immunodeficiency virus (HIV) integrates preferentially within active transcription units, whereas murine leukemia virus (MLV) integrate ... Full text Link to item Cite

Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis.

Journal Article PLoS Genet · April 2006 Featured Publication Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome characterized primarily by tumors of multiple endocrine glands. The gene for MEN1 encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was recently shown to i ... Full text Link to item Cite

The forkhead transcription factor FoxI1 remains bound to condensed mitotic chromosomes and stably remodels chromatin structure.

Journal Article Mol Cell Biol · January 2006 Featured Publication All forkhead (Fox) proteins contain a highly conserved DNA binding domain whose structure is remarkably similar to the winged-helix structures of histones H1 and H5. Little is known about Fox protein binding in the context of higher-order chromatin structu ... Full text Link to item Cite

Genome-wide mapping of DNase hypersensitive sites using massively parallel signature sequencing (MPSS).

Journal Article Genome Res · January 2006 Featured Publication A major goal in genomics is to understand how genes are regulated in different tissues, stages of development, diseases, and species. Mapping DNase I hypersensitive (HS) sites within nuclear chromatin is a powerful and well-established method of identifyin ... Full text Link to item Cite

Statistics for ChIP-chip and DNase hypersensitivity experiments on NimbleGen arrays.

Journal Article Methods Enzymol · 2006 Featured Publication Data obtained from high-density oligonucleotide tiling arrays present new computational challenges for users. This chapter presents ACME (Algorithm for Capturing Microarray Enrichment), a computer program developed for the analysis of data obtained using N ... Full text Link to item Cite

Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis.

Journal Article PLoS genetics · 2006 Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome characterized primarily by tumors of multiple endocrine glands. The gene for MEN1 encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was recently shown to i ... Full text Cite

Retroviral DNA integration: Viral and cellular determinants of target-site selection

Journal Article PLoS Pathogens · 2006 Retroviruses differ in their preferences for sites for viral DNA integration in the chromosomes of infected cells. Human immunodeficiency virus (HIV) integrates preferentially within active transcription units, whereas murine leukemia virus (MLV) integrate ... Full text Cite

The ENCODE (ENCyclopedia Of DNA Elements) Project.

Journal Article Science · October 22, 2004 The ENCyclopedia Of DNA Elements (ENCODE) Project aims to identify all functional elements in the human genome sequence. The pilot phase of the Project is focused on a specified 30 megabases (approximately 1%) of the human genome sequence and is organized ... Full text Link to item Cite

Identifying gene regulatory elements by genome-wide recovery of DNase hypersensitive sites.

Journal Article Proc Natl Acad Sci U S A · January 27, 2004 Featured Publication Analysis of the human genome sequence has identified approximately 25000-30000 protein-coding genes, but little is known about how most of these are regulated. Mapping DNase I hypersensitive (HS) sites has traditionally represented the gold-standard experi ... Full text Link to item Cite

Suppression of revertant fibers in mdx mice by expression of a functional dystrophin.

Journal Article Hum Mol Genet · November 15, 2001 Featured Publication Duchenne muscular dystrophy (DMD) is characterized by progressive muscle degeneration that results from the absence of dystrophin. Despite null mutations in the dystrophin gene, many DMD patients display a low percentage of dystrophin-positive fibers. Thes ... Full text Link to item Cite

Assembly of the dystrophin-associated protein complex does not require the dystrophin COOH-terminal domain.

Journal Article J Cell Biol · September 18, 2000 Featured Publication Dystrophin is a multidomain protein that links the actin cytoskeleton to laminin in the extracellular matrix through the dystrophin associated protein (DAP) complex. The COOH-terminal domain of dystrophin binds to two components of the DAP complex, syntrop ... Full text Link to item Cite

Interactions between beta 2-syntrophin and a family of microtubule-associated serine/threonine kinases.

Journal Article Nat Neurosci · July 1999 Featured Publication A screen for proteins that interact with beta 2-syntrophin led to the isolation of MAST205 (microtubule-associated serine/threonine kinase-205 kD) and a newly identified homologue, SAST (syntrophin-associated serine/threonine kinase). Binding studies showe ... Full text Link to item Cite