Foxa2 和 H2A.Z 介导胚胎干细胞分化过程中的核小体耗竭。
Foxa2 and H2A.Z mediate nucleosome depletion during embryonic stem cell differentiation.
机构信息
Department of Genetics and Institute of Diabetes, Obesity and Metabolism, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
出版信息
Cell. 2012 Dec 21;151(7):1608-16. doi: 10.1016/j.cell.2012.11.018.
Nucleosome occupancy is fundamental for establishing chromatin architecture. However, little is known about the relationship between nucleosome dynamics and initial cell lineage specification. Here, we determine the mechanisms that control global nucleosome dynamics during embryonic stem (ES) cell differentiation into endoderm. Both nucleosome depletion and de novo occupation occur during the differentiation process, with higher overall nucleosome density after differentiation. The variant histone H2A.Z and the winged helix transcription factor Foxa2 both act to regulate nucleosome depletion and gene activation, thus promoting ES cell differentiation, whereas DNA methylation promotes nucleosome occupation and suppresses gene expression. Nucleosome depletion during ES cell differentiation is dependent on Nap1l1-coupled SWI/SNF and INO80 chromatin remodeling complexes. Thus, both epigenetic and genetic regulators cooperate to control nucleosome dynamics during ES cell fate decisions.
核小体占据对于建立染色质结构至关重要。然而，人们对于核小体动力学与初始细胞谱系特化之间的关系知之甚少。在这里，我们确定了控制胚胎干细胞（ES 细胞）分化为内胚层过程中全局核小体动力学的机制。在分化过程中既会发生核小体耗竭，也会发生核小体从头占据，分化后整体核小体密度更高。变体组蛋白 H2A.Z 和翼状螺旋转录因子 Foxa2 都可以调节核小体耗竭和基因激活，从而促进 ES 细胞分化，而 DNA 甲基化则促进核小体占据和抑制基因表达。ES 细胞分化过程中的核小体耗竭依赖于 Nap1l1 偶联的 SWI/SNF 和 INO80 染色质重塑复合物。因此，表观遗传和遗传调控因子在 ES 细胞命运决定过程中共同控制核小体动力学。
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