H3K4me1 Distribution Predicts Transcription State and Poising at Promoters
H3K4me1 Distribution Predicts Transcription State and Poising at Promoters
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DOI：
10.3389/fcell.2020.00289
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发表时间：
2020-05-05
影响因子：
5.5
通讯作者：
Lesch, Bluma J.
中科院分区：
文献类型：
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作者：
Bae, Sunhee;Lesch, Bluma J.
组蛋白H3 （H3K4me1）赖氨酸4上的单甲基化通常与远端增强子相关，但H3K4me1也存在于转录起始位点附近的启动子区域。为了评估H3K4me1在决定启动子基因调控状态中的可能作用，我们使用分析策略检查了人类和小鼠生殖细胞中启动子周围的H3K4me1峰值密度，使我们能够评估不同表观遗传标记之间的关系。我们发现H3K4me1在活性启动子处呈现双峰模式，位于H3K4me3的两侧，或者在静止启动子处呈现单峰模式，与H3K4me3和H3K27me3重合。这种模式与基因表达水平相关，但与稳定的染色质状态（由H3K4me3和H3K27me3同时存在定义）的联系更紧密，而不是转录活性。这种模式在生殖细胞中尤为突出，但也存在于其他类型的细胞中，包括胚胎干细胞和分化的体细胞。我们提出H3K4me1是平衡表观遗传状态的关键特征，并提出该标记在表观遗传记忆中的可能作用。
Monomethylation on lysine 4 of histone H3 (H3K4me1) is commonly associated with distal enhancers, but H3K4me1 is also present at promoter regions proximal to transcription start sites. To assess a possible role for H3K4me1 in dictating gene regulatory states at promoters, we examined H3K4me1 peak density around promoters in human and mouse germ cells using an analytic strategy that allowed us to assess relationships between different epigenetic marks on a promoter-by-promoter basis. We found that H3K4me1 exhibits either a bimodal pattern at active promoters, where it flanks H3K4me3, or a unimodal pattern at poised promoters, where it coincides with both H3K4me3 and H3K27me3. This pattern is correlated with gene expression level, but is more strongly linked to a poised chromatin state, defined by the simultaneous presence of H3K4me3 and H3K27me3, than to transcriptional activity. The pattern is especially prominent in germ cells, but is also present in other cell types, including embryonic stem cells and differentiated somatic cells. We propose that H3K4me1 is a key feature of the poised epigenetic state, and suggest possible roles for this mark in epigenetic memory.