Cutting edge:: Changes in histone acetylation at the IL-4 and IFN-γ loci accompany Th1/Th2 differentiation
Cutting edge:: Changes in histone acetylation at the IL-4 and IFN-γ loci accompany Th1/Th2 differentiation
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DOI：
10.4049/jimmunol.169.2.647
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发表时间：
2002-07-15
影响因子：
4.4
通讯作者：
Flavell, RA
中科院分区：
文献类型：
--
作者：
Fields, PE;Kim, ST;Flavell, RA
外周T细胞分化伴随着标志性细胞因子基因座处的染色质变化。使用染色质免疫沉淀，我们证明，在组蛋白乙酰化的深刻增加发生在IFN-γ和IL-4位点在Th 1/Th 2分化。组蛋白乙酰化状态的这些变化是基因座和谱系特异性的，并且由转录因子Tbet和GATA 3以STAT依赖性方式维持。我们的研究结果提示了一种细胞因子位点激活的模型，其中TCR信号以非依赖于酪氨酸的方式启动染色质重塑和位点开放。随后，细胞因子信号传导通过在相关细胞因子基因座（IL-4或IFN-γ）处扩展和维持可接近状态来加强极化。在该模型中，GATA 3和Tbet作为转录维持因子，其保持基因座可接近转录机器。
Peripheral T cell differentiation is accompanied by chromatin changes at the signature cytokine loci. Using chromatin immunoprecipitation we demonstrate that profound increases in histone acetylation occur at the IFN-gamma and IL-4 loci during Th1/Th2 differentiation. These changes in histone acetylation status are locus and lineage specific, and are maintained by the transcription factors Tbet and GATA3 in a STAT-dependent manner. Our results suggest a model of cytokine locus activation in which TCR signals initiate chromatin remodeling and locus opening in a cytokine-independent fashion. Subsequently, cytokine signaling reinforces polarization by expanding and maintaining the accessible state at the relevant cytokine locus (IL-4 or IFN-gamma). In this model, GATA3 and Tbet serve as transcriptional maintenance factors, which keep the locus accessible to the transcriptional machinery.