Department of Genetics, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Edmond J. Safra campus 91904, Israel.
Nat Commun. 2012 Jun 19;3:910. doi: 10.1038/ncomms1915.
Embryonic stem cells are characterized by unique epigenetic features including decondensed chromatin and hyperdynamic association of chromatin proteins with chromatin. Here we investigate the potential mechanisms that regulate chromatin plasticity in embryonic stem cells. Using epigenetic drugs and mutant embryonic stem cells lacking various chromatin proteins, we find that histone acetylation, G9a-mediated histone H3 lysine 9 (H3K9) methylation and lamin A expression, all affect chromatin protein dynamics. Histone acetylation controls, almost exclusively, euchromatin protein dynamics; lamin A expression regulates heterochromatin protein dynamics, and G9a regulates both euchromatin and heterochromatin protein dynamics. In contrast, we find that DNA methylation and nucleosome repeat length have little or no effect on chromatin-binding protein dynamics in embryonic stem cells. Altered chromatin dynamics associates with perturbed embryonic stem cell differentiation. Together, these data provide mechanistic insights into the epigenetic pathways that are responsible for chromatin plasticity in embryonic stem cells, and indicate that the genome's epigenetic state modulates chromatin plasticity and differentiation potential of embryonic stem cells.
胚胎干细胞的特征是独特的表观遗传特征，包括去凝聚的染色质和染色质蛋白与染色质的超动态关联。在这里，我们研究了调节胚胎干细胞中染色质可塑性的潜在机制。使用表观遗传药物和缺乏各种染色质蛋白的突变胚胎干细胞，我们发现组蛋白乙酰化、G9a 介导的组蛋白 H3 赖氨酸 9（H3K9）甲基化和核纤层 A 表达均影响染色质蛋白动力学。组蛋白乙酰化几乎完全控制常染色质蛋白动力学；核纤层 A 表达调节异染色质蛋白动力学，而 G9a 调节常染色质和异染色质蛋白动力学。相比之下，我们发现 DNA 甲基化和核小体重复长度对胚胎干细胞中染色质结合蛋白动力学几乎没有影响。染色质动力学的改变与胚胎干细胞分化失调有关。总的来说，这些数据为负责胚胎干细胞中染色质可塑性的表观遗传途径提供了机制上的见解，并表明基因组的表观遗传状态调节胚胎干细胞的染色质可塑性和分化潜能。
