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全基因组分析转录因子 GATA3 介导的不同 T 细胞类型中的基因调控。

Genome-wide analyses of transcription factor GATA3-mediated gene regulation in distinct T cell types.

机构信息

Laboratory of Molecular Immunology, NHLBI, National Institutes of Health, 9000 Rockville Pike, Bethesda, MD 20892, USA.

出版信息

Immunity. 2011 Aug 26;35(2):299-311. doi: 10.1016/j.immuni.2011.08.007.

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.

摘要

转录因子 GATA3 在 T 细胞发育和辅助性 T 细胞 2(Th2)细胞分化过程中发挥着重要作用。为了了解 GATA3 介导的基因调控,我们在十个明确的发育和效应 T 淋巴细胞谱系中鉴定了全基因组 GATA3 结合位点。在胸腺中,GATA3 直接调节了许多关键因子,包括 Th-POK、Notch1 和 T 细胞受体亚基。在外周,GATA3 诱导了大量的 Th2 细胞特异性和非 Th2 细胞特异性基因,包括几个转录因子。我们的数据还表明,GATA3 在其 GATA3 结合位点附近的调控元件上调节许多靶基因的活性和抑制性组蛋白修饰。总的来说,尽管 GATA3 结合在各种 T 细胞谱系中表现出共享和细胞特异性模式,但许多基因都以细胞特异性的方式被 GATA3 正向或负向调控,这表明 GATA3 介导的基因调控强烈依赖于不同 T 细胞中存在的辅助因子。

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