A bivalent chromatin structure marks key developmental genes in embryonic stem cells
A bivalent chromatin structure marks key developmental genes in embryonic stem cells
复制标题
DOI：
10.1016/j.cell.2006.02.041
复制
发表时间：
2006-04-21
期刊：
影响因子：
64.5
通讯作者：
Lander, ES
中科院分区：
文献类型：
--
作者：
Bernstein, BE;Mikkelsen, TS;Lander, ES
哺乳动物基因组中最高度保守的非编码元件（HCNE）聚集在编码发育重要转录因子（TF）的基因富集区域内。这表明，富含HCNE的区域可能包含参与发展的关键监管控制。我们通过检测小鼠胚胎干细胞（ES）中56个富含HCNE的大基因座的组蛋白甲基化来探索这一点。我们确定了一种特定的修饰模式，称为“二价结构域”，由H3赖氨酸27甲基化的大区域和H3赖氨酸4甲基化的小区域组成。二价结构域倾向于与低水平表达的TF基因一致。我们提出，二价结构域沉默ES细胞中的发育基因，同时保持它们准备激活。我们还发现ES细胞中基因组序列与组蛋白甲基化之间存在惊人的对应关系，在分化的细胞中，组蛋白甲基化明显减弱。这些结果突出了DNA序列在定义最初的表观遗传景观中的重要性，并提出了一种新的基于染色质的维持多能性的机制。
The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development. We explored this by examining histone methylation in mouse embryonic stem (ES) cells across 56 large HCNE-rich loci. We identified a specific modification pattern, termed "bivalent domains," consisting of large regions of H3 lysine 27 methylation harboring smaller regions of H3 lysine 4 methylation. Bivalent domains tend to coincide with TF genes expressed at low levels. We propose that bivalent domains silence developmental genes in ES cells while keeping them poised for activation. We also found striking correspondences between genome sequence and histone methylation in ES cells, which become notably weaker in differentiated cells. These results highlight the importance of DNA sequence in defining the initial epigenetic landscape and suggest a novel chromatin-based mechanism for maintaining pluripotency.