Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation.
Discrete roles of STAT4 and STAT6 transcription factors in tuning epigenetic modifications and transcription during T helper cell differentiation.
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DOI：
10.1016/j.immuni.2010.06.003
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发表时间：
2010-06-25
期刊：
影响因子：
32.4
通讯作者：
Kanno Y
中科院分区：
文献类型：
--
作者：
Wei L;Vahedi G;Sun HW;Watford WT;Takatori H;Ramos HL;Takahashi H;Liang J;Gutierrez-Cruz G;Zang C;Peng W;O'Shea JJ;Kanno Y
信号转导和转录激活因子4(STAT4)和信号转导与转录激活因子6(STAT6)是辅助性T细胞的关键因子，但它们在诱导分化中的直接作用尚不清楚。使用染色质免疫沉淀和大规模平行测序，我们定量了STAT结合基因的完整补充，同时使用同源STAT缺陷小鼠的细胞来评估全球STAT依赖的表观遗传修饰和基因转录。STAT4和STAT6分别结合了4000多个具有不同结合基序的基因。两者都通过不同的表观遗传模式的组合，在维持染色质配置和核心基因子集的转录方面发挥了关键作用。在全球范围内，STAT4在促进主动表观遗传标记方面发挥了更主要的作用，而STAT6在拮抗抑制标记方面发挥了更突出的作用。被统计数据负面调控的基因簇也被识别出来，突显了以前未被认识到的压抑作用。因此，STAT4和STAT6在T辅助分子规范中起着广泛的调节作用。
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 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. Therefore, STAT4 and STAT6 play wide regulatory roles in T helper specification.
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影响因子：
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作者：
Ji, Hongkai;Jiang, Hui;Ma, Wenxiu;Johnson, David S.;Myers, Richard M.;Wong, Wing H.
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通讯作者：
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影响因子：
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作者：
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