Cfp1 is required for gene expression-dependent H3K4 trimethylation and H3K9 acetylation in embryonic stem cells.
Cfp1 is required for gene expression-dependent H3K4 trimethylation and H3K9 acetylation in embryonic stem cells.
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CFP1是基因表达依赖性H3K4三甲基化和H3K9乙酰化所必需的。
DOI：
10.1186/s13059-014-0451-x
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发表时间：
2014-09-04
期刊：
影响因子：
12.3
通讯作者：
Bird A
中科院分区：
文献类型：
--
作者：
Clouaire T;Webb S;Bird A
组蛋白H3赖氨酸4（H3 K4 me 3）的三甲基化以基因活性依赖的方式在启动子处积累。Set 1复合物负责体细胞中的大多数H3 K4 me 3，并含有保守的亚基Cfp 1，其涉及将Set 1复合物靶向哺乳动物中的CpG岛。在小鼠胚胎干细胞中，Cfp 1是H3 K4 me 3积累在组成型活性基因启动子所必需的，但不需要维持相关基因的稳态转录。在这里，我们表明，Cfp 1是工具的目标H3 K4 me 3启动子后，快速转录诱导响应外部刺激。令人惊讶的是，H3 K4 me 3的积累并不是确保适当转录输出所必需的，而是发挥基因特异性作用。我们还表明，Cfp 1依赖的H3 K4 me 3沉积有助于H3 K9乙酰化全基因组，这表明Cfp 1依赖的H3 K4 me 3调节整体H3 K9乙酰化动力学，是必要的组蛋白乙酰转移酶的招聘。最后，我们观察到增加的反义转录的开始和结束的基因，需要Cfp 1的准确沉积的H3 K4 me 3和H3 K9 ac。我们的研究结果为Cfp 1在建立复杂的活性启动子染色质状态中分配了关键作用，并揭示了染色质信号通路如何提供上下文依赖的转录结果。本文的在线版本（doi：10.1186/s13059-014-0451-x）包含补充材料，可供授权用户使用。
Trimethylation of histone H3 lysine 4 (H3K4me3) accumulates at promoters in a gene activity-dependent manner. The Set1 complex is responsible for most H3K4me3 in somatic cells and contains the conserved subunit Cfp1, which is implicated in targeting the Set1 complex to CpG islands in mammals. In mouse embryonic stem cells, Cfp1 is necessary for H3K4me3 accumulation at constitutively active gene promoters, but is not required to maintain steady-state transcription of the associated gene. Here we show that Cfp1 is instrumental for targeting H3K4me3 to promoters upon rapid transcriptional induction in response to external stimuli. Surprisingly, H3K4me3 accumulation is not required to ensure appropriate transcriptional output but rather plays gene-specific roles. We also show that Cfp1-dependent H3K4me3 deposition contributes to H3K9 acetylation genome-wide, suggesting that Cfp1-dependent H3K4me3 regulates overall H3K9 acetylation dynamics and is necessary for histone acetyl transferase recruitment. Finally, we observe increased antisense transcription at the start and end of genes that require Cfp1 for accurate deposition of H3K4me3 and H3K9ac. Our results assign a key role for Cfp1 in establishing a complex active promoter chromatin state and shed light on how chromatin signaling pathways provide context-dependent transcriptional outcomes. The online version of this article (doi:10.1186/s13059-014-0451-x) contains supplementary material, which is available to authorized users.
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