生物
H3K4me3
二价染色质
染色质
二价(发动机)
组蛋白
表观遗传学
有丝分裂
胚胎干细胞
细胞分化
遗传学
细胞生物学
组蛋白甲基化
细胞周期
诱导多能干细胞
DNA甲基化
基因
染色质重塑
基因表达
发起人
有机化学
化学
金属
作者
Rodrigo A. Grandy,Troy W. Whitfield,Hai Wu,Mark P. Fitzgerald,Jennifer VanOudenhove,Sayyed K. Zaidi,Martı́n Montecino,Jane B. Lian,André J. van Wijnen,Janet L. Stein,Janet L. Stein
摘要
Stem cell phenotypes are reflected by posttranslational histone modifications, and this chromatin-related memory must be mitotically inherited to maintain cell identity through proliferative expansion. In human embryonic stem cells (hESCs), bivalent genes with both activating (H3K4me3) and repressive (H3K27me3) histone modifications are essential to sustain pluripotency. Yet, the molecular mechanisms by which this epigenetic landscape is transferred to progeny cells remain to be established. By mapping genomic enrichment of H3K4me3/H3K27me3 in pure populations of hESCs in G2, mitotic, and G1 phases of the cell cycle, we found striking variations in the levels of H3K4me3 through the G2-M-G1 transition. Analysis of a representative set of bivalent genes revealed that chromatin modifiers involved in H3K4 methylation/demethylation are recruited to bivalent gene promoters in a cell cycle-dependent fashion. Interestingly, bivalent genes enriched with H3K4me3 exclusively during mitosis undergo the strongest upregulation after induction of differentiation. Furthermore, the histone modification signature of genes that remain bivalent in differentiated cells resolves into a cell cycle-independent pattern after lineage commitment. These results establish a new dimension of chromatin regulation important in the maintenance of pluripotency.
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