Timothy E Reddy

Journal Article bioRxiv · August 13, 2024 MOTIVATION: Allele-specific expression (ASE) analyses aim to detect imbalanced expression of maternal versus paternal copies of an autosomal gene. Such allelic imbalance can result from a variety of cis-acting causes, including disruptive mutations within ... Full text Link to item Cite

HyperCas12a enables highly-multiplexed epigenome editing screens.

Journal Article bioRxiv · July 9, 2024 Interactions between multiple genes or cis-regulatory elements (CREs) underlie a wide range of biological processes in both health and disease. High-throughput screens using dCas9 fused to epigenome editing domains have allowed researchers to assess the im ... Full text Link to item Cite

Mediator kinase inhibition impedes transcriptional plasticity and prevents resistance to ERK/MAPK-targeted therapy in KRAS-mutant cancers.

Journal Article NPJ Precis Oncol · May 31, 2024 Acquired resistance remains a major challenge for therapies targeting oncogene activated pathways. KRAS is the most frequently mutated oncogene in human cancers, yet strategies targeting its downstream signaling kinases have failed to produce durable treat ... Full text Link to item Cite

Multicenter integrated analysis of noncoding CRISPRi screens.

Journal Article Nat Methods · April 2024 The ENCODE Consortium's efforts to annotate noncoding cis-regulatory elements (CREs) have advanced our understanding of gene regulatory landscapes. Pooled, noncoding CRISPR screens offer a systematic approach to investigate cis-regulatory mechanisms. The E ... Full text Link to item Cite

Transcriptional and epigenetic regulators of human CD8+ T cell function identified through orthogonal CRISPR screens.

Journal Article Nat Genet · December 2023 Clinical response to adoptive T cell therapies is associated with the transcriptional and epigenetic state of the cell product. Thus, discovery of regulators of T cell gene networks and their corresponding phenotypes has potential to improve T cell therapi ... Full text Link to item Cite

Integrin α3 promotes TH17 cell polarization and extravasation during autoimmune neuroinflammation.

Journal Article Sci Immunol · October 20, 2023 Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) caused by CNS-infiltrating leukocytes, including TH17 cells that are critical mediators of disease pathogenesis. Although targeting leukocyte trafficking is effective in t ... Full text Link to item Cite

Cooperative regulation of coupled oncoprotein synthesis and stability in triple-negative breast cancer by EGFR and CDK12/13.

Journal Article Proc Natl Acad Sci U S A · September 19, 2023 Evidence has long suggested that epidermal growth factor receptor (EGFR) may play a prominent role in triple-negative breast cancer (TNBC) pathogenesis, but clinical trials of EGFR inhibitors have yielded disappointing results. Using a candidate drug scree ... Full text Link to item Cite

Adaptive sequence divergence forged new neurodevelopmental enhancers in humans.

Journal Article Cell · November 23, 2022 Searches for the genetic underpinnings of uniquely human traits have focused on human-specific divergence in conserved genomic regions, which reflects adaptive modifications of existing functional elements. However, the study of conserved regions excludes ... Full text Open Access Link to item Cite

ZBTB7A promotes virus-host homeostasis during human coronavirus 229E infection.

Journal Article Cell Rep · October 25, 2022 The cellular fate after infection with human coronaviruses (HCoVs) is typically death. Previous data suggest, however, that the transcriptional state of an individual cell may sometimes allow additional outcomes of infection. Here, to probe the range of in ... 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

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

Epigenome editing of the CFTR-locus for treatment of cystic fibrosis.

Journal Article J Cyst Fibros · January 2022 BACKGROUND: Mechanisms governing the diversity of CFTR gene expression throughout the body are complex. Multiple intronic and distal regulatory elements are responsible for regulating differential CFTR expression across tissues. METHODS: Drawing on publish ... Full text Link to item Cite

The functional genome: epigenetics and epigenomics

Chapter · January 1, 2022 All of our cells have the same genome sequence. The topic of this chapter is understanding how that shared and constant genome sequence acts differently in different cell types, responds to the environment, and changes throughout our lives. Chemical modifi ... Full text 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

Transgenic mice for in vivo epigenome editing with CRISPR-based systems.

Journal Article Nat Methods · August 2021 CRISPR-Cas9 technologies have dramatically increased the ease of targeting DNA sequences in the genomes of living systems. The fusion of chromatin-modifying domains to nuclease-deactivated Cas9 (dCas9) has enabled targeted epigenome editing in both culture ... Full text Link to item Cite

Glucocorticoid receptor triggers a reversible drug-tolerant dormancy state with acquired therapeutic vulnerabilities in lung cancer.

Journal Article Nat Commun · July 16, 2021 The glucocorticoid receptor (GR) regulates gene expression, governing aspects of homeostasis, but is also involved in cancer. Pharmacological GR activation is frequently used to alleviate therapy-related side-effects. While prior studies have shown GR acti ... Full text Link to item Cite

Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders.

Journal Article Nat Commun · June 25, 2021 Cellular heterogeneity in the human brain obscures the identification of robust cellular regulatory networks, which is necessary to understand the function of non-coding elements and the impact of non-coding genetic variation. Here we integrate genome-wide ... Full text Link to item Cite

Correcting signal biases and detecting regulatory elements in STARR-seq data.

Journal Article Genome Res · May 2021 High-throughput reporter assays such as self-transcribing active regulatory region sequencing (STARR-seq) have made it possible to measure regulatory element activity across the entire human genome at once. The resulting data, however, present substantial ... Full text Link to item Cite

AP-1 subunits converge promiscuously at enhancers to potentiate transcription.

Journal Article Genome Res · April 2021 The AP-1 transcription factor (TF) dimer contributes to many biological processes and environmental responses. AP-1 can be composed of many interchangeable subunits. Unambiguously determining the binding locations of these subunits in the human genome is c ... Full text Link to item Cite

Causal network inference from gene transcriptional time-series response to glucocorticoids.

Journal Article PLoS Comput Biol · January 2021 Gene regulatory network inference is essential to uncover complex relationships among gene pathways and inform downstream experiments, ultimately enabling regulatory network re-engineering. Network inference from transcriptional time-series data requires a ... Full text Link to item Cite

Bayesian Estimation of Allele-Specific Expression in the Presence of Phasing Uncertainty.

HyperCas12a enables highly-multiplexed epigenome editing screens.

Mediator kinase inhibition impedes transcriptional plasticity and prevents resistance to ERK/MAPK-targeted therapy in KRAS-mutant cancers.

Multicenter integrated analysis of noncoding CRISPRi screens.

Transcriptional and epigenetic regulators of human CD8+ T cell function identified through orthogonal CRISPR screens.

Integrin α3 promotes TH17 cell polarization and extravasation during autoimmune neuroinflammation.

Cooperative regulation of coupled oncoprotein synthesis and stability in triple-negative breast cancer by EGFR and CDK12/13.

Adaptive sequence divergence forged new neurodevelopmental enhancers in humans.

ZBTB7A promotes virus-host homeostasis during human coronavirus 229E infection.

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

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

Epigenome editing of the CFTR-locus for treatment of cystic fibrosis.

The functional genome: epigenetics and epigenomics

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

Transgenic mice for in vivo epigenome editing with CRISPR-based systems.

Glucocorticoid receptor triggers a reversible drug-tolerant dormancy state with acquired therapeutic vulnerabilities in lung cancer.

Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders.

Correcting signal biases and detecting regulatory elements in STARR-seq data.

AP-1 subunits converge promiscuously at enhancers to potentiate transcription.

Causal network inference from gene transcriptional time-series response to glucocorticoids.

Master Regulators and Cofactors of Human Neuronal Cell Fate Specification Identified by CRISPR Gene Activation Screens.

Journal Article Cell Rep · December 1, 2020 Technologies to reprogram cell-type specification have revolutionized the fields of regenerative medicine and disease modeling. Currently, the selection of fate-determining factors for cell reprogramming applications is typically a laborious and low-throug ... 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

Bayesian estimation of genetic regulatory effects in high-throughput reporter assays.

Journal Article Bioinformatics · January 15, 2020 MOTIVATION: High-throughput reporter assays dramatically improve our ability to assign function to noncoding genetic variants, by measuring allelic effects on gene expression in the controlled setting of a reporter gene. Unlike genetic association tests, s ... Full text Link to item Cite

c-Maf regulates the plasticity of group 3 innate lymphoid cells by restraining the type 1 program.

Journal Article J Exp Med · January 6, 2020 CCR6- group 3 innate lymphoid cells (ILC3s) are mediators of intestinal immunity and barrier function that possess the capacity to acquire type 1 effector features and fully convert into ILC1s. The molecular mechanisms governing such plasticity are undefin ... Full text Link to item Cite

Functional Genomics of Healthy and Pathological Fetal Membranes.

Journal Article Front Physiol · 2020 Premature preterm rupture of membranes (PPROM), rupture of fetal membranes before 37 weeks of gestation, is the leading identifiable cause of spontaneous preterm births. Often there is no obvious cause that is identified in a patient who presents with PPRO ... Full text Link to item Cite

Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells.

Conference Nat Biotechnol · December 2019 Class 2 CRISPR-Cas systems, such as Cas9 and Cas12, have been widely used to target DNA sequences in eukaryotic genomes. However, class 1 CRISPR-Cas systems, which represent about 90% of all CRISPR systems in nature, remain largely unexplored for genome en ... Full text Link to item Cite

Genome-wide quantification of the effects of DNA methylation on human gene regulation.

Journal Article Elife · December 21, 2018 Changes in DNA methylation are involved in development, disease, and the response to environmental conditions. However, not all regulatory elements are functionally methylation-dependent (MD). Here, we report a method, mSTARR-seq, that assesses the causal ... Full text Link to item Cite

Human genome-wide measurement of drug-responsive regulatory activity.

Journal Article Nat Commun · December 21, 2018 Environmental stimuli commonly act via changes in gene regulation. Human-genome-scale assays to measure such responses are indirect or require knowledge of the transcription factors (TFs) involved. Here, we present the use of human genome-wide high-through ... Full text Link to item Cite

Predicting gene structure changes resulting from genetic variants via exon definition features.

Journal Article Bioinformatics · November 1, 2018 MOTIVATION: Genetic variation that disrupts gene function by altering gene splicing between individuals can substantially influence traits and disease. In those cases, accurately predicting the effects of genetic variation on splicing can be highly valuabl ... 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

Clustering gene expression time series data using an infinite Gaussian process mixture model.

Journal Article PLoS Comput Biol · January 2018 Transcriptome-wide time series expression profiling is used to characterize the cellular response to environmental perturbations. The first step to analyzing transcriptional response data is often to cluster genes with similar responses. Here, we present a ... 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

A long-range flexible billboard model of gene activation.

Journal Article Transcription · August 8, 2017 Gene regulation is fundamentally important for the coordination of diverse biologic processes including homeostasis and responses to developmental and environmental stimuli. Transcription factor (TF) binding sites are one of the major functional subunits o ... 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

Transversions have larger regulatory effects than transitions.

Journal Article BMC Genomics · May 19, 2017 BACKGROUND: Transversions (Tv's) are more likely to alter the amino acid sequence of proteins than transitions (Ts's), and local deviations in the Ts:Tv ratio are indicative of evolutionary selection on genes. Whether the two different types of mutations h ... Full text Link to item Cite

High-throughput interpretation of gene structure changes in human and nonhuman resequencing data, using ACE.

Journal Article Bioinformatics · May 15, 2017 MOTIVATION: The accurate interpretation of genetic variants is critical for characterizing genotype-phenotype associations. Because the effects of genetic variants can depend strongly on their local genomic context, accurate genome annotations are essentia ... Full text Link to item Cite

Genetic determinants of adiponectin regulation revealed by pregnancy.

Journal Article Obesity (Silver Spring) · May 2017 OBJECTIVE: This study investigated genetic determinants of adiponectin during pregnancy to reveal novel biology of adipocyte regulation. METHODS: A genome-wide association study was conducted in 1,322 pregnant women from the Hyperglycemia and Adverse Pregn ... Full text Link to item Cite

Decoding the role of regulatory element polymorphisms in complex disease.

Journal Article Curr Opin Genet Dev · April 2017 Genetic variation in gene regulatory elements contributes to diverse human diseases, ranging from rare and severe developmental defects to common and complex diseases such as obesity and diabetes. Early examples of regulatory mechanisms of human diseases i ... Full text Link to item Cite

The Functional Genome: Epigenetics and Epigenomics

Chapter · January 1, 2017 All of our cells have the same genome sequence. The topic of this chapter is understanding how that shared and constant genome sequence acts differently in different cell types, responds to the environment, and changes throughout our lives. Chemical modifi ... Full text Cite

HKDC1 Is a Novel Hexokinase Involved in Whole-Body Glucose Use.

Journal Article Endocrinology · September 2016 In a recent genome-wide association study, hexokinase domain-containing protein 1, or HKDC1, was found to be associated with gestational glucose levels during 2-hour glucose tolerance tests at 28 weeks of pregnancy. Because our understanding of the mediato ... Full text Link to item Cite

Targeted Epigenetic Remodeling of Endogenous Loci by CRISPR/Cas9-Based Transcriptional Activators Directly Converts Fibroblasts to Neuronal Cells.

Journal Article Cell Stem Cell · September 1, 2016 Overexpression of exogenous fate-specifying transcription factors can directly reprogram differentiated somatic cells to target cell types. Here, we show that similar reprogramming can also be achieved through the direct activation of endogenous genes usin ... 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

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

Genomic approaches for understanding the genetics of complex disease.

Journal Article Genome Res · October 2015 There are thousands of known associations between genetic variants and complex human phenotypes, and the rate of novel discoveries is rapidly increasing. Translating those associations into knowledge of disease mechanisms remains a fundamental challenge be ... 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

Massively parallel quantification of the regulatory effects of noncoding genetic variation in a human cohort.

Journal Article Genome Res · August 2015 We report a novel high-throughput method to empirically quantify individual-specific regulatory element activity at the population scale. The approach combines targeted DNA capture with a high-throughput reporter gene expression assay. As demonstration, we ... Full text Link to item Cite

From Prescription to Transcription: Genome Sequence as Drug Target.

Journal Article Cell · July 2, 2015 Personalizing treatments to account for genetically mediated differences in drug responses is an exciting opportunity to improve patient outcomes. In this issue, Soccio et al. reveal new mechanisms by which non-coding variants alter the activity of the ant ... Full text Link to item Cite

Enhanced MyoD-induced transdifferentiation to a myogenic lineage by fusion to a potent transactivation domain.

Journal Article ACS Synth Biol · June 19, 2015 Genetic reprogramming holds great potential for disease modeling, drug screening, and regenerative medicine. Genetic reprogramming of mammalian cells is typically achieved by forced expression of natural transcription factors that control master gene netwo ... 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

485. Targeted Epigenome Editing by CRISPR/Cas9-Based Repressors for Silencing of Distal Regulatory Elements

Conference Molecular Therapy · May 2015 Full text Cite

Correction of dystrophin expression in cells from Duchenne muscular dystrophy patients through genomic excision of exon 51 by zinc finger nucleases

Journal Article Molecular Therapy · March 5, 2015 Duchenne muscular dystrophy (DMD) is caused by genetic mutations that result in the absence of dystrophin protein expression. Oligonucleotide-induced exon skipping can restore the dystrophin reading frame and protein production. However, this requires cont ... Full text Cite

Correction of dystrophin expression in cells from Duchenne muscular dystrophy patients through genomic excision of exon 51 by zinc finger nucleases.

Journal Article Mol Ther · March 2015 Duchenne muscular dystrophy (DMD) is caused by genetic mutations that result in the absence of dystrophin protein expression. Oligonucleotide-induced exon skipping can restore the dystrophin reading frame and protein production. However, this requires cont ... Full text Link to item Cite

Multiplex CRISPR/Cas9-based genome editing for correction of dystrophin mutations that cause Duchenne muscular dystrophy.

Journal Article Nat Commun · February 18, 2015 The CRISPR/Cas9 genome-editing platform is a promising technology to correct the genetic basis of hereditary diseases. The versatility, efficiency and multiplexing capabilities of the CRISPR/Cas9 system enable a variety of otherwise challenging gene correc ... Full text Link to item Cite

Coordinated regulatory variation associated with gestational hyperglycaemia regulates expression of the novel hexokinase HKDC1.

Journal Article Nat Commun · February 4, 2015 Maternal glucose levels during pregnancy impact the developing fetus, affecting metabolic health both early and later on in life. Both genetic and environmental factors influence maternal metabolism, but little is known about the genetic mechanisms that al ... Full text Link to item Cite

New insights into gestational glucose metabolism: lessons learned from 21st century approaches.

Journal Article Diabetes · February 2015 Pregnancy presents a unique physiological challenge that requires changes coordinated by placentally and non-placentally derived hormones to prepare the mother for the metabolic stress presented by fetal development and to ensure appropriate nutrient alloc ... Full text Link to item Cite

CRISPR/Cas9-Based Transcriptional Repressors for Control of Human Gene Expression

Conference MOLECULAR THERAPY · May 1, 2014 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

Erratum: Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies (Diabetes (2013) 62 (3282-3291))

Journal Article Diabetes · October 1, 2013 Full text 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

Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies.

Journal Article Diabetes · September 2013 Maternal metabolism during pregnancy impacts the developing fetus, affecting offspring birth weight and adiposity. This has important implications for metabolic health later in life (e.g., offspring of mothers with pre-existing or gestational diabetes mell ... Full text Link to item Cite

The chromosome 3q25 genomic region is associated with measures of adiposity in newborns in a multi-ethnic genome-wide association study.

Journal Article Hum Mol Genet · September 1, 2013 Newborns characterized as large and small for gestational age are at risk for increased mortality and morbidity during the first year of life as well as for obesity and dysglycemia as children and adults. The intrauterine environment and fetal genes contri ... Full text Link to item Cite

Evidence for multiple roles for grainyhead-like 2 in the establishment and maintenance of human mucociliary airway epithelium.[corrected].

Journal Article Proc Natl Acad Sci U S A · June 4, 2013 Most of the airways of the human lung are lined by an epithelium made up of ciliated and secretory luminal cells and undifferentiated basal progenitor cells. The integrity of this epithelium and its ability to act as a selective barrier are critical for no ... 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

Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner.

Journal Article Genome Res · November 2012 Endogenous estrogens that are synthesized in the body impact gene regulation by activating estrogen receptors in diverse cell types. Exogenous compounds that have estrogenic properties can also be found circulating in the blood in both children and adults. ... Full text Link to item Cite

Architecture of the human regulatory network derived from ENCODE data.

Journal Article Nature · September 6, 2012 Transcription factors bind in a combinatorial fashion to specify the on-and-off states of genes; the ensemble of these binding events forms a regulatory network, constituting the wiring diagram for a cell. To examine the principles of the human transcripti ... 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

ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia.

Journal Article Genome Res · September 2012 Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite it ... 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

Corrigendum to:Agent-based modeling of the context dependency in T cell recognition.

Journal Article J Theor Biol · June 21, 2012 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 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

Allele-specific distribution of RNA polymerase II on female X chromosomes.

Journal Article Hum Mol Genet · October 15, 2011 While the distribution of RNA polymerase II (PolII) in a variety of complex genomes is correlated with gene expression, the presence of PolII at a gene does not necessarily indicate active expression. Various patterns of PolII binding have been described g ... Full text Link to item Cite

Analysis of DNA methylation in a three-generation family reveals widespread genetic influence on epigenetic regulation.

Journal Article PLoS Genet · August 2011 The methylation of cytosines in CpG dinucleotides is essential for cellular differentiation and the progression of many cancers, and it plays an important role in gametic imprinting. To assess variation and inheritance of genome-wide patterns of DNA methyl ... Full text 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

Genomic determination of the glucocorticoid response reveals unexpected mechanisms of gene regulation.

Journal Article Genome Res · December 2009 The glucocorticoid steroid hormone cortisol is released by the adrenal glands in response to stress and serves as a messenger in circadian rhythms. Transcriptional responses to this hormonal signal are mediated by the glucocorticoid receptor (GR). We deter ... Full text Link to item Cite

Distinct DNA methylation patterns characterize differentiated human embryonic stem cells and developing human fetal liver.

Journal Article Genome Res · June 2009 To investigate the role of DNA methylation during human development, we developed Methyl-seq, a method that assays DNA methylation at more than 90,000 regions throughout the genome. Performing Methyl-seq on human embryonic stem cells (hESCs), their derivat ... Full text Link to item Cite

Binding site graphs: a new graph theoretical framework for prediction of transcription factor binding sites.

Journal Article PLoS Comput Biol · May 2007 Computational prediction of nucleotide binding specificity for transcription factors remains a fundamental and largely unsolved problem. Determination of binding positions is a prerequisite for research in gene regulation, a major mechanism controlling phe ... Full text Link to item Cite

Positional clustering improves computational binding site detection and identifies novel cis-regulatory sites in mammalian GABAA receptor subunit genes.

Journal Article Nucleic Acids Res · 2007 Understanding transcription factor (TF) mediated control of gene expression remains a major challenge at the interface of computational and experimental biology. Computational techniques predicting TF-binding site specificity are frequently unreliable. On ... Full text Link to item Cite

Agent-based modeling of the context dependency in T cell recognition.

Journal Article J Theor Biol · October 21, 2005 Antigen recognition by T cells is a key event in the adaptive immune response. T cells scan the surface of antigen-presenting cells (APCs) or target cells for specific peptides bound to MHC molecules. In the physiological setting, a typical APC presents te ... Full text Link to item Cite

Assessing transcription factor motif drift from noisy decoy sequences.

Journal Article Genome Inform · 2005 Genome scale identification of transcription factor binding sites (TFBS) is fundamental to understanding the complexities of mRNA expression at both the cell and organismal levels. While high-throughput experimental methods provide associations between tra ... Link to item Cite

Comparisons of predicted genetic modules: identification of co-expressed genes through module gene flow.

Journal Article Genome Inform · 2004 A question of fundamental importance is the definition and identification of modules from microarray experiments. A wide variety of techniques have been used to gain insight into the elucidation of such modules. One problem, however, is the inability to di ... Link to item Cite

A cellular automata model of early t cell recognition

Journal Article Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) · January 1, 2004 T cells are key components of the immune system, recognizing the presence of foreign antigens by coming in direct contact with specialized antigen-presenting cells (APCs) and scanning the array of surface molecules presented by the APC. During the first 60 ... Full text Cite