title: Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types.
abstract: The transcription factor GATA3 plays an essential role during T cell development and T helper 2 (Th2) cell differentiation. To understand GATA3-mediated gene regulation, we identified genome-wide GATA3 binding sites in ten well-defined developmental and effector T lymphocyte lineages. In the thymus, GATA3 directly regulated many critical factors, including Th-POK, Notch1, and T cell receptor subunits. In the periphery, GATA3 induced a large number of Th2 cell-specific as well as Th2 cell-nonspecific genes, including several transcription factors. Our data also indicate that GATA3 regulates both active and repressive histone modifications of many target genes at their regulatory elements near GATA3 binding sites. Overall, although GATA3 binding exhibited both shared and cell-specific patterns among various T cell lineages, many genes were either positively or negatively regulated by GATA3 in a cell type-specific manner, suggesting that GATA3-mediated gene regulation depends strongly on cofactors existing in different T cells.
authors.affiliation: Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Wei
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Abraham
authors.forename: Ryoji
authors.initials: R
authors.lastname: Yagi
authors.forename: Raja
authors.initials: R
authors.lastname: Jothi
authors.forename: Kairong
authors.initials: K
authors.lastname: Cui
authors.forename: Suveena
authors.initials: S
authors.lastname: Sharma
authors.forename: Leelavati
authors.initials: L
authors.lastname: Narlikar
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Northrup
authors.forename: Qingsong
authors.initials: Q
authors.lastname: Tang
authors.forename: William E
authors.initials: WE
authors.lastname: Paul
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhu
authors.forename: Keji
authors.initials: K
authors.lastname: Zhao
mesh_terms: D000818:Animals; D019070:Cell Lineage / Q000235:genetics; D019175:DNA Methylation; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D016678:Genome / Q000276:immunology; D055106:Genome-Wide Association Study; D006657:Histones / Q000235:genetics / Q000378:metabolism; D038041:Lymphopoiesis / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D050990:GATA3 Transcription Factor; D006657:Histones; D050505:Mutant Proteins; D051881:Receptor, Notch1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors; C494748:Gata3 protein, mouse; C497211:Zbtb7b protein, mouse