Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.
Cell Stem Cell. 2010 May 7;6(5):479-91. doi: 10.1016/j.stem.2010.03.018.
Human embryonic stem cells (hESCs) share an identical genome with lineage-committed cells, yet possess the remarkable properties of self-renewal and pluripotency. The diverse cellular properties in different cells have been attributed to their distinct epigenomes, but how much epigenomes differ remains unclear. Here, we report that epigenomic landscapes in hESCs and lineage-committed cells are drastically different. By comparing the chromatin-modification profiles and DNA methylomes in hESCs and primary fibroblasts, we find that nearly one-third of the genome differs in chromatin structure. Most changes arise from dramatic redistributions of repressive H3K9me3 and H3K27me3 marks, which form blocks that significantly expand in fibroblasts. A large number of potential regulatory sequences also exhibit a high degree of dynamics in chromatin modifications and DNA methylation. Additionally, we observe novel, context-dependent relationships between DNA methylation and chromatin modifications. Our results provide new insights into epigenetic mechanisms underlying properties of pluripotency and cell fate commitment.
人类胚胎干细胞 (hESCs) 与谱系定向细胞具有相同的基因组,但具有自我更新和多能性的显著特性。不同细胞中不同的细胞特性归因于它们不同的表观基因组,但表观基因组的差异有多大尚不清楚。在这里,我们报告 hESCs 和谱系定向细胞中的表观基因组景观有很大的不同。通过比较 hESCs 和原代成纤维细胞中的染色质修饰谱和 DNA 甲基化组,我们发现近三分之一的基因组在染色质结构上存在差异。大多数变化源于抑制性 H3K9me3 和 H3K27me3 标记的显著重新分布,这些标记在成纤维细胞中形成显著扩大的块。大量潜在的调控序列在染色质修饰和 DNA 甲基化方面也表现出高度的动态性。此外,我们还观察到 DNA 甲基化和染色质修饰之间新的、上下文相关的关系。我们的研究结果为多能性和细胞命运决定的表观遗传机制提供了新的见解。
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