Scholars@Duke
Yuan Zhuang

Yuan Zhuang

Professor of Integrative Immunobiology
Integrative Immunobiology
yzhuang@duke.edu
Box 3010 DUMC, 328 Jones Building, Durham, NC 27710
328 Jones Building, 207 Resear, Box 3010 DUMC, Durham, NC 27710

Selected Publications

E proteins control the development of NKγδT cells through their invariant T cell receptor.

Journal Article Nat Commun · June 13, 2024 T cell receptor (TCR) signaling regulates important developmental transitions, partly through induction of the E protein antagonist, Id3. Although normal γδ T cell development depends on Id3, Id3 deficiency produces different phenotypes in distinct γδ T ce ... Full text Link to item Cite

E protein binding at the Tcra enhancer promotes Tcra repertoire diversity.

Journal Article Front Immunol · 2023 V(D)J recombination of antigen receptor loci is a highly developmentally regulated process. During T lymphocyte development, recombination of the Tcra gene occurs in CD4+CD8+ double positive (DP) thymocytes and requires the Tcra enhancer (Eα). E proteins a ... Full text Link to item Cite

Loss of Zfp335 triggers cGAS/STING-dependent apoptosis of post-β selection thymocytes.

Journal Article Nat Commun · October 6, 2022 Production of a functional peripheral T cell compartment typically involves massive expansion of the bone marrow progenitors that seed the thymus. There are two main phases of expansion during T cell development, following T lineage commitment of double-ne ... Full text Link to item Cite

Trav15-dv6 family Tcrd rearrangements diversify the Tcra repertoire.

Journal Article J Exp Med · February 7, 2022 The Tcra repertoire is generated by multiple rounds of Vα-Jα rearrangement. However, Tcrd recombination precedes Tcra recombination within the complex Tcra-Tcrd locus. Here, by ablating Tcrd recombination, we report that Tcrd rearrangement broadens primary ... Full text Link to item Cite

Anti-tumor effects of an ID antagonist with no observed acquired resistance.

Journal Article NPJ breast cancer · May 2021 ID proteins are helix-loop-helix (HLH) transcriptional regulators frequently overexpressed in cancer. ID proteins inhibit basic-HLH transcription factors often blocking differentiation and sustaining proliferation. A small-molecule, AGX51, targets ID prote ... Full text Cite

Conversion of effector CD4+ T cells to a CD8+ MHC II-recognizing lineage.

Journal Article Cell Mol Immunol · January 2021 CD4+ and CD8+ T cells are dichotomous lineages in adaptive immunity. While conventionally viewed as distinct fates that are fixed after thymic development, accumulating evidence indicates that these two populations can exhibit significant lineage plasticit ... Full text Link to item Cite

A mosaic analysis system with Cre or Tomato expression in the mouse.

Journal Article Proc Natl Acad Sci U S A · November 10, 2020 Somatic mutations are major genetic contributors to cancers and many other age-related diseases. Many disease-causing somatic mutations can initiate clonal growth prior to the appearance of any disease symptoms, yet experimental models that can be used to ... Full text Link to item Cite

TCR Repertoires of Thymic Conventional and Regulatory T Cells: Identification and Characterization of Both Unique and Shared TCR Sequences.

Journal Article J Immunol · February 15, 2020 Featured Publication Thymic regulatory T cells (tTreg) are critical in the maintenance of normal T cell immunity and tolerance. The role of TCR in tTreg selection remains incompletely understood. In this study, we assessed TCRα and TCRβ sequences of mouse tTreg and thymic conv ... Full text Link to item Cite

VisTCR: An Interactive Software for T Cell Repertoire Sequencing Data Analysis.

Journal Article Front Genet · 2020 Recent progress in high throughput sequencing technologies has provided an opportunity to probe T cell receptor (TCR) repertoire, bringing about an explosion of TCR sequencing data and analysis tools. For easier and more heuristic analysis TCR sequencing d ... Full text Link to item Cite

Putative biomarkers for predicting tumor sample purity based on gene expression data.

Journal Article BMC Genomics · December 27, 2019 BACKGROUND: Tumor purity is the percent of cancer cells present in a sample of tumor tissue. The non-cancerous cells (immune cells, fibroblasts, etc.) have an important role in tumor biology. The ability to determine tumor purity is important to understand ... Full text Link to item Cite

The whole-genome landscape of Burkitt lymphoma subtypes.

Journal Article Blood · November 7, 2019 Featured Publication Burkitt lymphoma (BL) is an aggressive, MYC-driven lymphoma comprising 3 distinct clinical subtypes: sporadic BLs that occur worldwide, endemic BLs that occur predominantly in sub-Saharan Africa, and immunodeficiency-associated BLs that occur primarily in ... Full text Link to item Cite

E-protein-regulated expression of CXCR4 adheres preselection thymocytes to the thymic cortex.

Journal Article J Exp Med · August 5, 2019 Featured Publication Preselection thymocytes are normally retained in the thymic cortex, but the mechanisms responsible remain incompletely understood. We now report that deletion of genes encoding the E-protein transcription factors E2A and HEB disorders chemokine receptor ex ... Full text Link to item Cite

Genetic models reveal origin, persistence and non-redundant functions of IL-17-producing γδ T cells.

Journal Article J Exp Med · December 3, 2018 Featured Publication γδ T cells are highly conserved in jawed vertebrates, suggesting an essential role in the immune system. However, γδ T cell-deficient Tcrd -/- mice display surprisingly mild phenotypes. We hypothesized that the lack of γδ T cells in constitutive Tcrd -/- m ... Full text Link to item Cite

Id3 Restricts γδ NKT Cell Expansion by Controlling Egr2 and c-Myc Activity.

Journal Article J Immunol · September 1, 2018 Featured Publication γδ NKT cells are neonatal-derived γδ T lymphocytes that are grouped together with invariant NKT cells based on their shared innate-like developmental program characterized by the transcription factor PLZF (promyelocytic leukemia zinc finger). Previous stud ... Full text Link to item Cite

Paradoxical role of Id proteins in regulating tumorigenic potential of lymphoid cells.

Journal Article Front Med · August 2018 Featured Publication A family of transcription factors known as Id proteins, or inhibitor of DNA binding and differentiation, is capable of regulating cell proliferation, survival and differentiation, and is often upregulated in multiple types of tumors. Due to their ability t ... Full text Link to item Cite

Disruption of Gen1 Causes Congenital Anomalies of the Kidney and Urinary Tract in Mice.

Journal Article Int J Biol Sci · 2018 Congenital anomalies of the kidney and urinary tract (CAKUT) are among the most common developmental defects in humans. Despite of several known CAKUT-related loci (HNF1B, PAX2, EYA1, etc.), the genetic etiology of CAKUT remains to be elucidated for most p ... Full text Link to item Cite

Id Proteins Suppress E2A-Driven Invariant Natural Killer T Cell Development prior to TCR Selection.

Journal Article Front Immunol · 2018 Featured Publication A family of transcription factors known as E proteins, and their antagonists, Id proteins, regulate T cell differentiation at critical developmental checkpoints. Id proteins promote the differentiation of conventional αβ T cells and suppress the expansion ... Full text Link to item Cite

DNA-PK facilitates piggyBac transposition by promoting paired-end complex formation.

Journal Article Proc Natl Acad Sci U S A · July 11, 2017 The involvement of host factors is critical to our understanding of underlying mechanisms of transposition and the applications of transposon-based technologies. Modified piggyBac (PB) is one of the most potent transposon systems in mammals. However, varyi ... Full text Link to item Cite

Tcrd Rearrangement Redirects a Processive Tcra Recombination Program to Expand the Tcra Repertoire.

Journal Article Cell reports · June 2017 Featured Publication Adaptive immunity depends on diverse T cell receptor repertoires generated by variable, diversity, and joining (V[D]J) recombination. Here, we define the principles by which combinatorial diversity is generated in the murine Tcra repertoire. Tcra and Tcrd ... Full text Cite

Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2.

Journal Article J Exp Med · May 1, 2017 Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenc ... Full text Link to item Cite

Id2 Collaborates with Id3 To Suppress Invariant NKT and Innate-like Tumors.

Journal Article J Immunol · April 15, 2017 Featured Publication Inhibitor of DNA binding (Id) proteins, including Id1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins is associated with a broad spectrum of tumors, recent ... Full text Link to item Cite

The Histone Methyltransferase Ash1l is Required for Epidermal Homeostasis in Mice.

Journal Article Sci Rep · April 4, 2017 Epidermal homeostasis under normal and healing conditions are critical for the physical and functional maintenance of the skin barrier. It requires a proper balance between keratinocyte proliferation and differentiation under genetic and epigenetic regulat ... Full text Link to item Cite

The Genetic Basis of Hepatosplenic T-cell Lymphoma.

Journal Article Cancer Discov · April 2017 Featured Publication Hepatosplenic T-cell lymphoma (HSTL) is a rare and lethal lymphoma; the genetic drivers of this disease are unknown. Through whole-exome sequencing of 68 HSTLs, we define recurrently mutated driver genes and copy-number alterations in the disease. Chromati ... Full text Link to item Cite

Disruption of Gpr45 causes reduced hypothalamic POMC expression and obesity.

Journal Article J Clin Invest · September 1, 2016 Featured Publication A rise in the occurrence of obesity has driven exploration of its underlying genetic basis and potential targets for intervention. GWAS studies have identified obesity susceptibility pathways involving several neuropeptides that control energy homeostasis, ... Full text Link to item Cite

Glimpse of natural selection of long-lived T-cell clones in healthy life.

Journal Article Proc Natl Acad Sci U S A · August 30, 2016 Featured Publication Homeostatic maintenance of T cells with broad clonal diversity is influenced by both continuing output of young T cells from the thymus and ongoing turnover of preexisting clones in the periphery. In the absence of infection, self and commensal antigens ar ... Full text Link to item Cite

Generation of a Mouse Full-length Balancer with Versatile Cassette-shuttling Selection Strategy.

Journal Article Int J Biol Sci · 2016 Featured Publication Balancer chromosomes are important tools for a variety of genetic manipulations in lower model organisms, owing to their ability to suppress recombination. In mouse, however, such effort has not been accomplished, mostly due to the size of the chromosomes ... Full text Link to item Cite

Differential Requirements of TCR Signaling in Homeostatic Maintenance and Function of Dendritic Epidermal T Cells.

Journal Article J Immunol · November 1, 2015 Featured Publication Dendritic epidermal T cells (DETCs) are generated exclusively in the fetal thymus and maintained in the skin epithelium throughout postnatal life of the mouse. DETCs have restricted antigenic specificity as a result of their exclusive usage of a canonical ... Full text Link to item Cite

PP6 controls T cell development and homeostasis by negatively regulating distal TCR signaling.

Journal Article J Immunol · February 15, 2015 Featured Publication T cell development and homeostasis are both regulated by TCR signals. Protein phosphorylation and dephosphorylation, which are catalyzed by protein kinases and phosphatases, respectively, serve as important switches controlling multiple downstream pathways ... Full text Link to item Cite

Orchestration of invariant natural killer T cell development by E and Id proteins.

Journal Article Crit Rev Immunol · 2015 Featured Publication Natural killer T (NKT) cells are αβ T cells that express a semi-invariant T-cell receptor (TCR) along with natural killer (NK) cell markers and have an innate cell-like ability to produce a myriad of cytokines very quickly upon antigen exposure and subsequ ... Full text Link to item Cite

Aberrant production of IL-13 by T cells promotes exocrinopathy in Id3 knockout mice.

Journal Article Cytokine · October 2014 Featured Publication Elevated levels of the cytokine IL-13 has been found to be associated with autoimmune diseases, including Sjögren's Syndrome. However, whether IL-13 plays a causative role in disease development is not known and cannot be easily studied in humans. Our prev ... Full text Link to item Cite

Mesenchymal high-grade glioma is maintained by the ID-RAP1 axis.

Journal Article J Clin Invest · September 2, 2014 Featured Publication Full text Link to item Cite

A piggyBac insertion disrupts Foxl2 expression that mimics BPES syndrome in mice.

Journal Article Hum Mol Genet · July 15, 2014 Blepharophimosis, ptosis, epicanthus inversus syndrome (BPES) is an autosomal dominant genetic disorder characterized by small palpebral fissures and other craniofacial malformations, often with (type I) but could also without (type II) premature ovarian f ... Full text Link to item Cite

Rhbdd3 controls autoimmunity by suppressing the production of IL-6 by dendritic cells via K27-linked ubiquitination of the regulator NEMO.

Journal Article Nat Immunol · July 2014 Excessive activation of dendritic cells (DCs) leads to the development of autoimmune and inflammatory diseases, which has prompted a search for regulators of DC activation. Here we report that Rhbdd3, a member of the rhomboid family of proteases, suppresse ... Full text Link to item Cite

Mst1/Mst2 regulate development and function of regulatory T cells through modulation of Foxo1/Foxo3 stability in autoimmune disease.

Journal Article J Immunol · February 15, 2014 Foxp3 expression and regulatory T cell (Treg) development are critical for maintaining dominant tolerance and preventing autoimmune diseases. Human MST1 deficiency causes a novel primary immunodeficiency syndrome accompanied by autoimmune manifestations. H ... Full text Link to item Cite

Id3 and Id2 act as a dual safety mechanism in regulating the development and population size of innate-like γδ T cells.

Journal Article J Immunol · February 1, 2014 Featured Publication The innate-like T cells expressing Vγ1.1 and Vδ6.3 represent a unique T cell lineage sharing features with both the γδ T and the invariant NKT cells. The population size of Vγ1.1(+)Vδ6.3(+) T cells is tightly controlled and usually contributes to a very sm ... Full text Link to item Cite

E proteins in lymphocyte development and lymphoid diseases.

Journal Article Curr Top Dev Biol · 2014 As members of the basic helix-loop-helix (bHLH) family of transcription factors, E proteins function in the immune system by directing and maintaining a vast transcriptional network that regulates cell survival, proliferation, differentiation, and function ... Full text Link to item Cite

Combined deletion of Id2 and Id3 genes reveals multiple roles for E proteins in invariant NKT cell development and expansion.

Journal Article J Immunol · November 15, 2013 Featured Publication The invariant NKT (iNKT) cells represent a unique group of αβ T cells that have been classified based on their exclusive usage of the invariant Vα14Jα18 TCRα-chain and their innate-like effector function. Thus far, the transcriptional programs that control ... Full text Link to item Cite

Tracking proliferative history in lymphocyte development with cre-mediated sister chromatid recombination.

Journal Article PLoS Genet · October 2013 Featured Publication Tracking and isolating live cells based on their proliferative history in live animals remains a technical challenge in animal studies. We have designed a genetic marking system for tracking the proliferative frequency and history of lymphocytes during the ... Full text Link to item Cite

piggyBac as a high-capacity transgenesis and gene-therapy vector in human cells and mice.

Journal Article Dis Model Mech · May 2013 The stable genomic integration and expression of a large transgene is a major hurdle in gene therapy. We show that the modified piggyBac (PB) transposon system can be used to introduce a 207 kb genomic DNA fragment containing the RORγ/γt locus into human c ... Full text Link to item Cite

PiggyBac Mutagenesis and Information Center

Journal Article TRANSGENIC RESEARCH · February 1, 2013 Link to item Cite

Mesenchymal high-grade glioma is maintained by the ID-RAP1 axis.

Journal Article J Clin Invest · January 2013 High-grade gliomas (HGGs) are incurable brain tumors that are characterized by the presence of glioma-initiating cells (GICs). GICs are essential to tumor aggressiveness and retain the capacity for self-renewal and multilineage differentiation as long as t ... Full text Link to item Cite

Inner nuclear envelope proteins SUN1 and SUN2 play a prominent role in the DNA damage response.

Journal Article Curr Biol · September 11, 2012 The DNA damage response (DDR) and DNA repair are critical for maintaining genomic stability and evading many human diseases. Recent findings indicate that accumulation of SUN1, a nuclear envelope (NE) protein, is a significant pathogenic event in Emery-Dre ... Full text Link to item Cite

Transcriptional regulator Id2 is required for the CD4 T cell immune response in the development of experimental autoimmune encephalomyelitis.

Journal Article J Immunol · August 1, 2012 Featured Publication An effective immune response to Ag challenge is critically dependent on the size of the effector cell population generated from clonal activation of Ag-specific T cells. The transcription network involved in regulating the size of the effector population, ... Full text Link to item Cite

Generation of Dhx9-deficient clones in T-cell development with a mitotic recombination technique.

Journal Article Genesis · July 2012 Featured Publication Mitotic recombination is an effective tool for generating mutant clones in somatic tissues. Because of difficulties associated with detecting and quantifying mutant clones in mice, this technique is limited to analysis of growth-related phenotypes induced ... Full text Link to item Cite

Id proteins synchronize stemness and anchorage to the niche of neural stem cells.

Journal Article Nat Cell Biol · April 22, 2012 Stem-cell functions require activation of stem-cell-intrinsic transcriptional programs and extracellular interaction with a niche microenvironment. How the transcriptional machinery controls residency of stem cells in the niche is unknown. Here we show tha ... Full text Link to item Cite

E protein transcription factors are required for the development of CD4(+) lineage T cells.

Journal Article Immunity · March 23, 2012 Featured Publication The double-positive (DP) to single-positive (SP) transition during T cell development is initiated by downregulation of the E protein transcription factors HEB and E2A. Here, we have demonstrated that in addition to regulating the onset of this transition, ... Full text Link to item Cite

Contribution of IL-13 to early exocrinopathy in Id3-/- mice.

Journal Article Mol Immunol · October 2011 Featured Publication Id3-/- mice represent a model for T cell mediated primary Sjogren's syndrome (PSS). An intriguing feature of this disease model is the early appearance of impaired salivary function or exocrinopathy prior to lymphocytic infiltration of the salivary glands. ... Full text Link to item Cite

Stage-specific functions of E-proteins at the β-selection and T-cell receptor checkpoints during thymocyte development.

Journal Article Immunol Res · April 2011 Featured Publication The E-protein transcription factors E2A and HEB function in a lineage- and stage-specific manner to orchestrate many critical events throughout lymphocyte development. The function of E-proteins in both B- and T-lymphocyte development has been extensively ... Full text Link to item Cite

Modeling Sjögren's syndrome with Id3 conditional knockout mice.

Journal Article Immunol Lett · March 30, 2011 Featured Publication The Id3 gene has been shown to play important roles in the development and function of broad tissue types including B and T cells. Id3 deficient mice develop autoimmune disease similar to human Sjögren's syndrome. Both B and T lymphocytes have been implica ... Full text Link to item Cite

KASH protein Syne-2/Nesprin-2 and SUN proteins SUN1/2 mediate nuclear migration during mammalian retinal development.

Journal Article Hum Mol Genet · March 15, 2011 Nuclear movement relative to cell bodies is a fundamental process during certain aspects of mammalian retinal development. During the generation of photoreceptor cells in the cell division cycle, the nuclei of progenitors oscillate between the apical and b ... Full text Link to item Cite

Control of the differentiation of regulatory T cells and T(H)17 cells by the DNA-binding inhibitor Id3.

Journal Article Nat Immunol · January 2011 The molecular mechanisms that direct transcription of the gene encoding the transcription factor Foxp3 in CD4(+) T cells remain ill-defined. We show here that deletion of the DNA-binding inhibitor Id3 resulted in the defective generation of Foxp3(+) regula ... Full text Link to item Cite

Adam10 is essential for early embryonic cardiovascular development.

Journal Article Dev Dyn · October 2010 Notch pathway has been demonstrated to regulate cardiovascular development. One important step in Notch pathway is the cleavage of Notch receptor, during which an intracellular fragment of Notch protein is released to activate downstream genes. It is still ... Full text Link to item Cite

Generation and analysis of partially haploid cells with Cre-mediated chromosome deletion in the lymphoid system.

Journal Article J Biol Chem · August 20, 2010 Featured Publication The fast accumulation of mutant mouse strains in recent years has provided an invaluable resource for phenotype-based genetic screens. However, study of lymphoid phenotypes can be obscured or impractical if homozygous mutations cause early embryonic defect ... Full text Link to item Cite

Disruption of lysosome function promotes tumor growth and metastasis in Drosophila.

Journal Article J Biol Chem · July 9, 2010 Lysosome function is essential to many physiological processes. It has been suggested that deregulation of lysosome function could contribute to cancer. Through a genetic screen in Drosophila, we have discovered that mutations disrupting lysosomal degradat ... Full text Link to item Cite

Endothelial SUR-8 acts in an ERK-independent pathway during atrioventricular cushion development.

Journal Article Dev Dyn · July 2010 SUR-8, a conserved leucine-rich repeats protein, was first identified as a positive regulator of Ras pathway in Caenorhabditis elegans. Biochemical studies indicated that SUR-8 interacts with Ras and Raf, leading to the elevated ERK activity. However, the ... Full text Link to item Cite

SUN1/2 and Syne/Nesprin-1/2 complexes connect centrosome to the nucleus during neurogenesis and neuronal migration in mice.

Journal Article Neuron · October 29, 2009 Nuclear movement is critical during neurogenesis and neuronal migration, which are fundamental for mammalian brain development. Although dynein, Lis1, and other cytoplasmic proteins are known for their roles in connecting microtubules to the nucleus during ... Full text Link to item Cite

Ras promotes cell survival by antagonizing both JNK and Hid signals in the Drosophila eye.

Journal Article BMC Dev Biol · October 20, 2009 BACKGROUND: Programmed cell death, or apoptosis, is a fundamental physiological process during normal development or in pathological conditions. The activation of apoptosis can be elicited by numerous signalling pathways. Ras is known to mediate anti-apopt ... Full text Link to item Cite

A tamoxifen inducible knock-in allele for investigation of E2A function.

Journal Article BMC Dev Biol · October 12, 2009 Featured Publication BACKGROUND: E-proteins are transcription factors important for the development of a variety of cell types, including neural, muscle and lymphocytes of the immune system. E2A, the best characterized E-protein family member in mammals, has been shown to have ... Full text Link to item Cite

C-terminal deletion of the atrophin-1 protein results in growth retardation but not neurodegeneration in mice.

Journal Article Dev Dyn · October 2009 Dentatorubral-pallidoluysian atrophy (DRPLA) is a dominant hereditary neurodegenerative disorder caused by the expansion of a poly-glutamine (poly-Q) repeat in Atrophin-1 protein. Ectopic expression of a poly-Q expanded human Atrophin-1 is sufficient to in ... Full text Link to item Cite

A cell-intrinsic role for Mst1 in regulating thymocyte egress.

Journal Article J Immunol · September 15, 2009 The MST1 kinase was recently identified as playing an essential role in the promotion of lymphocyte polarization and adhesion stimulated by chemokines and TCR signaling. However, the physiological relevance of the Mst1 pathway in thymocyte development is n ... Full text Link to item Cite

Pre-TCR signaling inactivates Notch1 transcription by antagonizing E2A.

Journal Article Genes Dev · July 15, 2009 Precise control of the timing and magnitude of Notch signaling is essential for the normal development of many tissues, but the feedback loops that regulate Notch are poorly understood. Developing T cells provide an excellent context to address this issue. ... Full text Link to item Cite

SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice.

Journal Article Proc Natl Acad Sci U S A · June 23, 2009 How the nuclei in mammalian skeletal muscle fibers properly position themselves relative to the cell body is an interesting and important cell biology question. In the syncytial skeletal muscle cells, more than 100 nuclei are evenly distributed at the peri ... Full text Link to item Cite

Id3 restricts the developmental potential of gamma delta lineage during thymopoiesis.

Journal Article J Immunol · May 1, 2009 Featured Publication Most T cell progenitors develop into the alphabeta T cell lineage with the exception of a small fraction contributing to the gammadelta lineage throughout postnatal life. T cell progenitors usually commit to the alphabeta lineage upon the expression of a f ... Full text Link to item Cite

Roles for Id3 in T Cell Development and Autoimmunity

Conference JOURNAL OF IMMUNOLOGY · April 1, 2009 Link to item Cite

MEKK3 is essential for lymphopenia-induced T cell proliferation and survival.

Journal Article J Immunol · March 15, 2009 T cell homeostasis is crucial for maintaining an efficient and balanced T cell immunity. The interaction between TCR and self peptide (sp) MHC ligands is known to be the key driving force in this process, and it is believed to be functionally and mechanist ... Full text Link to item Cite

Regulation of V(D)J recombination by E-protein transcription factors.

Journal Article Adv Exp Med Biol · 2009 Featured Publication Extensive study of the E-proteins E2A and HEB duringlymphocyte development has revealed various functions for these bHLH transcription factors in regulating V(D)J recombination in both B- and T-cells. The study of E-proteins in mammals began with the ident ... Full text Link to item Cite

A large-scale functional approach to uncover human genes and pathways in Drosophila.

Journal Article Cell Res · November 2008 We demonstrate the feasibility of performing a systematic screen for human gene functions in Drosophila by assaying for their ability to induce overexpression phenotypes. Over 1 500 transgenic fly lines corresponding to 236 human genes have been establishe ... Full text Link to item Cite

Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development.

Journal Article Cell · October 3, 2008 Plasmacytoid dendritic cells (PDCs) represent a unique immune cell type specialized in type I interferon (IFN) secretion in response to viral nucleic acids. The molecular control of PDC lineage specification has been poorly understood. We report that basic ... Full text Link to item Cite

E proteins are required to activate germline transcription of the TCR Vbeta8.2 gene.

Journal Article Eur J Immunol · October 2008 Featured Publication Each TCR Vbeta gene is regulated by an individual Vbeta promoter, which becomes active prior to V(D) J recombination and drives germline transcription. It has been shown that Vbeta gene locus activation and recombination are dependent on the Vbeta promoter ... Full text Link to item Cite

ADAM10 is essential for proteolytic activation of Notch during thymocyte development.

Journal Article Int Immunol · September 2008 Notch signaling pathway has been shown to play essential roles in T lymphocyte development. Activation of Notch requires a sequential proteolytic cleavage, which converts Notch from the full-length membrane-bound form to a transcriptionally active intracel ... Full text Link to item Cite

Id3 controls the developmental window of gamma delta T Cells

Conference JOURNAL OF INVESTIGATIVE DERMATOLOGY · April 1, 2008 Link to item Cite

A mitotic recombination system for mouse chromosome 17.

Journal Article Proc Natl Acad Sci U S A · March 18, 2008 Featured Publication Mitotic recombination between homologous chromosomes is a genetic technique for mosaic analysis in model organisms. The general application of this technique in the mouse depends on establishment of effective recombination systems for individual chromosome ... Full text Link to item Cite

Id3 controls the developmental window of γδ T cells

Journal Article FASEB JOURNAL · 2008 Cite

PBmice: an integrated database system of piggyBac (PB) insertional mutations and their characterizations in mice.

Journal Article Nucleic Acids Res · January 2008 DNA transposon piggyBac (PB) is a newly established mutagen for large-scale mutagenesis in mice. We have designed and implemented an integrated database system called PBmice (PB Mutagenesis Information CEnter) for storing, retrieving and displaying the inf ... Full text Link to item Cite

Acquisition of a functional T cell receptor during T lymphocyte development is enforced by HEB and E2A transcription factors.

Journal Article Immunity · December 2007 Featured Publication The T cell receptor (TCR) is required for positive selection and the subsequent transition from the CD4(+)CD8(+) double-positive (DP) to the CD4(+) or CD8(+) single-positive (SP) stage of alphabeta T cell development. The molecular mechanism that maintains ... Full text Link to item Cite

B-lymphocyte depletion ameliorates Sjögren's syndrome in Id3 knockout mice.

Journal Article Immunology · September 2007 Featured Publication Sjögren's syndrome is an autoimmune disease in which immune cells chronically attack the lachrymal and salivary glands. The Id3 knockout mouse is a newly established animal model for primary Sjögren's syndrome. To address the role of B cells in Sjögren's s ... Full text Link to item Cite

SUN1 is required for telomere attachment to nuclear envelope and gametogenesis in mice.

Journal Article Dev Cell · June 2007 Prior to the pairing and recombination between homologous chromosomes during meiosis, telomeres attach to the nuclear envelope and form a transient cluster. However, the protein factors mediating meiotic telomere attachment to the nuclear envelope and the ... Full text Link to item Cite

Germline transcription from T-cell receptor Vbeta gene is uncoupled from allelic exclusion.

Journal Article EMBO J · May 2, 2007 Featured Publication Allelic exclusion operates in B and T lymphocytes to ensure clonal expression of antigen receptors after V(D)J recombination. Germline transcription, which proceeds V(D)J recombination, has been postulated to provide an instructive signal for allelic exclu ... Full text Link to item Cite

E2A and HEB are required to block thymocyte proliferation prior to pre-TCR expression.

Journal Article J Immunol · May 1, 2007 Featured Publication Thymocytes undergoing TCRbeta gene rearrangements are maintained in a low or nonproliferating state during early T cell development. This block in cell cycle progression is not released until the expression of a functional pre-TCR, which is composed of a s ... Full text Link to item Cite

Syne-1 and Syne-2 play crucial roles in myonuclear anchorage and motor neuron innervation.

Journal Article Development · March 2007 Proper nuclear positioning is important to cell function in many biological processes during animal development. In certain cells, the KASH-domain-containing proteins have been shown to be associated with the nuclear envelope, and to be involved in both nu ... Full text Link to item Cite

Muscle atrophy in transgenic mice expressing a human TSC1 transgene.

Journal Article FEBS Lett · October 16, 2006 Muscle mass is regulated by a wide range of hormonal and nutritional signals, such as insulin and IGF. Tuberous sclerosis complex (TSC) is an inherited hamartoma disease with tumor growth in numerous organs. TSC is caused by mutation in either TSC1 or TSC2 ... Full text Link to item Cite

E2A promotes the survival of precursor and mature B lymphocytes.

Journal Article J Immunol · August 15, 2006 Featured Publication The basic helix-loop-helix transcription factor E2A is an essential regulator of B lymphocyte lineage commitment and is required to activate the expression of numerous B lineage-specific genes. Studies involving ectopic expression of Id proteins, which inh ... Full text Link to item Cite

Sodium butyrate ameliorates histone hypoacetylation and neurodegenerative phenotypes in a mouse model for DRPLA.

Journal Article J Biol Chem · May 5, 2006 Dentatorubral-pallidoluysian atrophy (DRPLA) is a progressive neurodegenerative disease caused by polyglutamine expansion within the Atrophin-1 protein. To study the mechanism of this disease and to test potential therapeutic methods, we established Atro-1 ... Full text Link to item Cite

E2A and IRF-4/Pip promote chromatin modification and transcription of the immunoglobulin kappa locus in pre-B cells.

Journal Article Mol Cell Biol · February 2006 Featured Publication The immunoglobulin kappa light chain (Igkappa) locus is regulated in a lineage- and stage-specific manner during B-cell development. The highly restricted timing of V to J gene recombination at the pre-B-cell stage is under the control of two enhancers, th ... Full text Link to item Cite

The KASH domain protein MSP-300 plays an essential role in nuclear anchoring during Drosophila oogenesis.

Journal Article Dev Biol · January 15, 2006 During late stages of Drosophila oogenesis, the cytoplasm of nurse cells in the egg chamber is rapidly transferred ("dumped") to oocytes, while the nurse cell nuclei are anchored by a mechanism that involves the actin cytoskeleton. The factors that mediate ... Full text Link to item Cite

Efficient transposition of the piggyBac (PB) transposon in mammalian cells and mice.

Journal Article Cell · August 12, 2005 Featured Publication Transposable elements have been routinely used for genetic manipulation in lower organisms, including generating transgenic animals and insertional mutagenesis. In contrast, the usage of transposons in mice and other vertebrate systems is still limited due ... Full text Link to item Cite

New insights into E-protein function in lymphocyte development.

Journal Article Trends Immunol · June 2005 Featured Publication Lymphocyte development has long served as an experimental paradigm, revealing fundamental mechanisms of gene regulation and cellular differentiation in mammals. The study of E-protein-mediated transcriptional regulation in lymphocyte development provides a ... Full text Link to item Cite

Ubiquitous expression of mRFP1 in transgenic mice.

Journal Article Genesis · June 2005 Fluorescent proteins provide a powerful means to track gene expression and cellular behaviors in the study of model organisms such as mice. Among the new generation of fluorescent protein markers, the monomeric red fluorescent protein mRFP1 is particularly ... Full text Link to item Cite

Differential functions for the transcription factor E2A in positive and negative gene regulation in pre-B lymphocytes.

Journal Article J Biol Chem · October 22, 2004 Featured Publication The transcription factors encoded by the E2A gene have been shown to play essential roles in the initiation and progression of lymphocyte development. However, there is still a lack of comprehensive understanding of E2A downstream genes in B-cell developme ... Full text Link to item Cite

A T cell intrinsic role of Id3 in a mouse model for primary Sjogren's syndrome.

Journal Article Immunity · October 2004 Featured Publication Sjogren's syndrome is an autoimmune disease with clinical hallmarks of keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth). The genetic basis of this autoimmune disease is poorly understood. Id3 is an immediate early-response gene in growth re ... Full text Link to item Cite

Regulation of E2A gene expression in B-lymphocyte development.

Journal Article Mol Immunol · March 2004 Featured Publication Biochemical and genetic studies have demonstrated that transcription factors encoded by the E2A gene are essential in regulating B lineage specific gene expression and B lineage commitment. However, the mechanism by which E2A regulates B lineage commitment ... Full text Link to item Cite

Altered T-dependent antigen responses and development of autoimmune symptoms in mice lacking E2A in T lymphocytes.

Journal Article Immunology · February 2004 Featured Publication E2A has been shown to be an important transcription factor downstream of the T-cell receptor (TCR) signal during T-cell development. The TCR signal is known to elicit different cellular responses at different stages of T-cell development. Whether E2A is st ... Full text Link to item Cite

A conserved transcriptional enhancer regulates RAG gene expression in developing B cells.

Journal Article Immunity · July 2003 Although expression of the RAG1 and RAG2 genes is essential for lymphocyte development, the mechanisms responsible for the lymphoid- and developmental stage-specific regulation of these genes are poorly understood. We have identified a novel, evolutionaril ... Full text Link to item Cite

Regulation of E2A activities by histone acetyltransferases in B lymphocyte development.

Journal Article J Biol Chem · January 24, 2003 Featured Publication Genetic studies have demonstrated that the basic helix-loop-helix protein E2A is an essential transcription factor in B lymphocyte lineage commitment and differentiation. However, the mechanism underlying E2A-mediated transcription regulation is not fully ... Full text Link to item Cite

Regulation of early lymphocyte development by E2A family proteins.

Journal Article Semin Immunol · December 2002 Lymphocytes develop from hematopoietic stem cells through a series of highly regulated differentiation events in the bone marrow and thymus. A number of transcription factors are known to collaborate in controlling the timing and specificity of gene expres ... Full text Link to item Cite

Identification of E2A target genes in B lymphocyte development by using a gene tagging-based chromatin immunoprecipitation system.

Journal Article Proc Natl Acad Sci U S A · November 12, 2002 Featured Publication The transcription factors encoded by the E2A gene are known to be essential for B lymphocyte development, and ectopic expression or gene inactivation studies have revealed several potential lineage-specific E2A target genes. However, it remains unknown whe ... Full text Link to item Cite

Disruption of Mekk2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction.

Journal Article Mol Cell Biol · August 2002 MEKK2 is a member of the mitogen-activated protein kinase (MAPK) kinase kinase gene family involved in regulating multiple MAPK signaling pathways. To elucidate the in vivo function of MEKK2, we generated mice carrying a targeted mutation in the Mekk2 locu ... Full text Link to item Cite

FKBP12 is the only FK506 binding protein mediating T-cell inhibition by the immunosuppressant FK506.

Journal Article Transplantation · June 15, 2002 BACKGROUND: FK506-binding proteins (FKBP) are immunophilins that interact with the immunosuppressive drugs FK506 and rapamycin. Several FKBP family members such as FKBP12, FKBP12.6, and FKBP51 are expressed in T cells. It has been speculated that these FKB ... Full text Link to item Cite

An analysis of T cell intrinsic roles of E2A by conditional gene disruption in the thymus.

Journal Article J Immunol · April 15, 2002 Featured Publication The importance of E2A transcription factors in T cell development has been demonstrated in studies of E2A-deficient mice, which display abnormal T cell development and a high frequency of T cell lymphomas. Because E2A expression is not restricted to the T ... Full text Link to item Cite

Functions of E2A-HEB heterodimers in T-cell development revealed by a dominant negative mutation of HEB.

Journal Article Mol Cell Biol · September 2000 Featured Publication Lymphocyte development and differentiation are regulated by the basic helix-loop-helix (bHLH) transcription factors encoded by the E2A and HEB genes. These bHLH proteins bind to E-box enhancers in the form of homodimers or heterodimers and, consequently, a ... Full text Link to item Cite

Developmental regulation of the E2A gene in lymphopoiesis revealed by an E2AGFP allele

Journal Article FASEB JOURNAL · April 20, 2000 Featured Publication Link to item Cite

Mekk3 is essential for early embryonic cardiovascular development.

Journal Article Nat Genet · March 2000 The early development of blood vessels consists of two phases, vasculogenesis and angiogenesis, which involve distinct and also overlapping molecular regulators, but the intracellular signal transduction pathways involved in these processes have not been w ... Full text Link to item Cite

A genetic investigation of E2A function in lymphocyte development.

Journal Article Immunol Res · 2000 Lymphocytes are derived from hematopoietic stem cells (HSC) following a series of regulated differentiation events. Multipotent HSCs become committed to the B cell lineage in bone marrow and the T cell lineage in the thymus after receiving appropriate sign ... Full text Link to item Cite

Id1 and Id3 are required for neurogenesis, angiogenesis and vascularization of tumour xenografts.

Journal Article Nature · October 14, 1999 Featured Publication Id proteins may control cell differentiation by interfering with DNA binding of transcription factors. Here we show that targeted disruption of the dominant negative helix-loop-helix proteins Id1 and Id3 in mice results in premature withdrawal of neuroblas ... Full text Link to item Cite

A novel role for HEB downstream or parallel to the pre-TCR signaling pathway during alpha beta thymopoiesis.

Journal Article J Immunol · September 15, 1999 Featured Publication TCR gene rearrangement and expression are central to the development of clonal T lymphocytes. The pre-TCR complex provides the first signal instructing differentiation and proliferation events during the transition from CD4-CD8-TCR- double negative (DN) st ... Link to item Cite

Impaired immune responses and B-cell proliferation in mice lacking the Id3 gene.

Journal Article Mol Cell Biol · September 1999 Featured Publication B-lymphocyte activation and proliferation induced by the B-cell receptor (BCR) signals are important steps in the initiation of humoral immune responses. How the BCR signals are translated by nuclear transcription factors into cell cycle progression is poo ... Full text Link to item Cite

Targeted disruption of Smad3 reveals an essential role in transforming growth factor beta-mediated signal transduction.

Journal Article Mol Cell Biol · April 1999 The Smads are a family of nine related proteins which function as signaling intermediates for the transforming growth factor beta (TGF-beta) superfamily of ligands. To discern the in vivo functions of one of these Smads, Smad3, we generated mice harboring ... Full text Link to item Cite

Controlling lymphopoiesis with a combinatorial E-protein code.

Journal Article Cold Spring Harb Symp Quant Biol · 1999 Full text Link to item Cite

Functional replacement of the mouse E2A gene with a human HEB cDNA.

Journal Article Mol Cell Biol · June 1998 Featured Publication The mammalian E2A, HEB, and E2-2 genes encode a unique class of basic helix-loop-helix (bHLH) transcription factors that are evolutionarily conserved and essential for embryonic and postnatal development. While the structural and functional similarities am ... Full text Link to item Cite

High incidence of T-cell tumors in E2A-null mice and E2A/Id1 double-knockout mice.

Journal Article Mol Cell Biol · December 1997 Featured Publication The basic-helix-loop-helix (bHLH) proteins encoded by the E2A gene are broadly expressed transcription regulators which function through binding to the E-box enhancer sequences. The DNA binding activities of E2A proteins are directly inhibited upon dimeriz ... Full text Link to item Cite

Analysis of the role of E2A-encoded proteins in insulin gene transcription.

Journal Article Mol Endocrinol · October 1997 Pancreatic beta-cell type-specific transcription of the insulin gene is mediated, in part, by factors in the basic helix-loop-helix (bHLH) family that act on a site within the insulin enhancer, termed the E1-box. Expression from this element is regulated b ... Full text Link to item Cite

B-lymphocyte development is regulated by the combined dosage of three basic helix-loop-helix genes, E2A, E2-2, and HEB.

Journal Article Mol Cell Biol · June 1996 Featured Publication B-lymphocyte development requires the basic helix-loop-helix proteins encoded by the E2A gene. In this study, the control mechanism of E2A was further explored by disruption of the E2A-related genes, E2-2 and HEB. In contrast to E2A, E2-2 and HEB are not e ... Full text Link to item Cite

Targeted deletion of 5'HS2 of the murine beta-globin LCR reveals that it is not essential for proper regulation of the beta-globin locus.

Journal Article Genes Dev · September 15, 1995 The beta-globin locus control region (LCR) is a complex regulatory element that is essential for the appropriate red cell-specific expression of all cis-linked beta-globin genes. Of the five hypersensitive sites that define the LCR, only 5'HS2 has been sho ... Full text Link to item Cite

The helix-loop-helix gene E2A is required for B cell formation.

Journal Article Cell · December 2, 1994 Featured Publication Heterodimers between tissue-specific basic-helix-loop-helix proteins and the gene products of E2A play major roles in determining tissue-specific cell fate. To understand the broad role of E2A in development, we have generated E2A mutant mice following hom ... Full text Link to item Cite

Helix-loop-helix transcription factors E12 and E47 are not essential for skeletal or cardiac myogenesis, erythropoiesis, chondrogenesis, or neurogenesis.

Journal Article Proc Natl Acad Sci U S A · December 15, 1992 Featured Publication E12 and E47 are two non-tissue-specific helix-loop-helix (HLH) transcription factors encoded by the E2A gene. Previous studies suggested that they are involved in regulation of differentiation in many tissue types including muscle, blood, and nerve through ... Full text Link to item Cite

The myoD gene family: nodal point during specification of the muscle cell lineage.

Journal Article Science · February 15, 1991 The myoD gene converts many differentiated cell types into muscle. MyoD is a member of the basic-helix-loop-helix family of proteins; this 68-amino acid domain in MyoD is necessary and sufficient for myogenesis. MyoD binds cooperatively to muscle-specific ... Full text Link to item Cite

The conserved dinucleotide AG of the 3' splice site may be recognized twice during in vitro splicing of mammalian mRNA precursors.

Journal Article Gene · June 15, 1990 Featured Publication We have previously used site-directed mutagenesis to introduce an additional branch site into the first intron of the human beta-globin gene at nt -24 between the natural branch site (nt -37) and the normal 3' splice site (nt -1). We found that either the ... Full text Link to item Cite

A compensatory base change in human U2 snRNA can suppress a branch site mutation.

Journal Article Genes Dev · October 1989 Featured Publication We have developed an assay to test whether U2 snRNA can base-pair with the branch site during mammalian mRNA splicing. The beta 110 point mutation (GG----AG) within the first intron of human beta-globin generates a new 3' splice site that is preferentially ... Full text Link to item Cite

UACUAAC is the preferred branch site for mammalian mRNA splicing.

Journal Article Proc Natl Acad Sci U S A · April 1989 Featured Publication The conserved branch-site sequence UAC-UAAC is known to form base pairs with the complementary sequence GUAGUA in U2 small nuclear RNA (snRNA) during mRNA splicing in the yeast Saccharomyces cerevisiae. Although the GUAGUA element is conserved in mammalian ... Full text Link to item Cite

The natural 5' splice site of simian virus 40 large T antigen can be improved by increasing the base complementarity to U1 RNA.

Journal Article Mol Cell Biol · August 1987 Featured Publication The use of alternative 5' splice sites in the simian virus 40 early-transcription unit controls the ratio of large T to small t antigen during viral infection. To study the regulation of these alternative 5' splice sites, we made two mutants which improve ... Full text Link to item Cite

A compensatory base change in U1 snRNA suppresses a 5' splice site mutation.

Journal Article Cell · September 12, 1986 Featured Publication Indirect evidence suggests that the 5' end of U1 snRNA recognizes the 5' splice site in mRNA precursors by complementary base pairing. To test this hypothesis, we asked whether point mutations in the alternative 12S and 13S 5' splice sites of the adenoviru ... Full text Link to item Cite