Discrete Roles of STAT4 and STAT6 Transcription Factors in Tuning Epigenetic Modifications and Transcription during T Helper Cell Differentiation

被引：262

作者：

Wei, Lai ^{[1
]}

Vahedi, Golnaz ^{[1
]}

Sun, Hong-Wei ^{[2
]}

Watford, Wendy T. ^{[1
]}

Takatori, Hiroaki ^{[1
]}

Ramos, Haydee L. ^{[1
]}

Takahashi, Hayato ^{[1
]}

Liang, Jonathan ^{[1
]}

Gutierrez-Cruz, Gustavo ^{[3
]}

Zang, Chongzhi ^{[4
]}

Peng, Weiqun ^{[4
]}

O'Shea, John J. ^{[1
]}

Kanno, Yuka ^{[1
]}

机构：

[1] NIAMS, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA

[2] NIAMS, Biodata Min & Discovery Sect, NIH, Bethesda, MD 20892 USA

[3] NIAMS, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA

[4] George Washington Univ, Dept Phys, Washington, DC 20052 USA

来源：

IMMUNITY | 2010年 / 32卷 / 06期

关键词：

CHIP-SEQ DATA; GENOME-WIDE IDENTIFICATION; TARGET GENES; HISTONE MODIFICATIONS; FATE DETERMINATION; INTERFERON-GAMMA; BINDING-SITES; FACTOR GATA-3; DNA-BINDING; EXPRESSION;

D O I：

10.1016/j.immuni.2010.06.003

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Signal transducer and activator of transcription 4 (STAT4) and STAT6 are key factors in the specification of helper T cells; however, their direct roles in driving differentiation are not well understood. Using chromatin immunoprecipitation and massive parallel sequencing, we quantitated the full complement of STAT-bound genes, concurrently assessing global STAT-dependent epigenetic modifications and gene transcription by using cells from cognate STAT-deficient mice. STAT4 and STAT6 each bound over 4000 genes with distinct binding motifs. Both played critical roles in maintaining chromatin configuration and transcription of a core subset of genes through the combination of different epigenetic patterns. Globally, STAT4 had a more dominant role in promoting active epigenetic marks, whereas STAT6 had a more prominent role in antagonizing repressive marks. Clusters of genes negatively regulated by STATs were also identified, highlighting previously unappreciated repressive roles of STATs. Therefore, STAT4 and STAT6 play wide regulatory roles in T helper cell specification.

引用

页码：840 / 851

页数：12

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