Bae Sunhee, Lesch Bluma J
Department of Genetics, Yale School of Medicine, New Haven, CT, United States.
Yale Cancer Center, Yale School of Medicine, New Haven, CT, United States.
Front Cell Dev Biol. 2020 May 5;8:289. doi: 10.3389/fcell.2020.00289. eCollection 2020.
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.
组蛋白H3赖氨酸4位点的单甲基化(H3K4me1)通常与远端增强子相关,但H3K4me1也存在于转录起始位点近端的启动子区域。为了评估H3K4me1在决定启动子处基因调控状态方面的可能作用,我们使用一种分析策略,在人和小鼠生殖细胞中检测了启动子周围的H3K4me1峰密度,该策略使我们能够在逐个启动子的基础上评估不同表观遗传标记之间的关系。我们发现,H3K4me1在活跃启动子处呈现双峰模式,位于H3K4me3两侧;而在 poised 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,但与由H3K4me3和H3K27me3同时存在所定义的 poised 染色质状态的联系更强,而不是与转录活性相关。这种模式在生殖细胞中尤为突出,但在其他细胞类型中也存在,包括胚胎干细胞和分化的体细胞。我们提出H3K4me1是 poised 表观遗传状态的一个关键特征,并暗示了该标记在表观遗传记忆中的可能作用。