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多能性和分化的表观遗传调控。

Epigenetic regulation of pluripotency and differentiation.

机构信息

From the Department of Chemical Physiology, Center for Regenerative Medicine, The Scripps Research Institute, La Jolla, CA 92037.

出版信息

Circ Res. 2014 Jul 7;115(2):311-24. doi: 10.1161/CIRCRESAHA.115.301517.

Abstract

The precise, temporal order of gene expression during development is critical to ensure proper lineage commitment, cell fate determination, and ultimately, organogenesis. Epigenetic regulation of chromatin structure is fundamental to the activation or repression of genes during embryonic development. In recent years, there has been an explosion of research relating to various modes of epigenetic regulation, such as DNA methylation, post-translational histone tail modifications, noncoding RNA control of chromatin structure, and nucleosome remodeling. Technological advances in genome-wide epigenetic profiling and pluripotent stem cell differentiation have been primary drivers for elucidating the epigenetic control of cellular identity during development and nuclear reprogramming. Not only do epigenetic mechanisms regulate transcriptional states in a cell-type-specific manner but also they establish higher order genomic topology and nuclear architecture. Here, we review the epigenetic control of pluripotency and changes associated with pluripotent stem cell differentiation. We focus on DNA methylation, DNA demethylation, and common histone tail modifications. Finally, we briefly discuss epigenetic heterogeneity among pluripotent stem cell lines and the influence of epigenetic patterns on genome topology.

摘要

发育过程中基因表达的精确时间顺序对于确保正确的谱系承诺、细胞命运决定以及最终的器官发生至关重要。染色质结构的表观遗传调控对于胚胎发育过程中基因的激活或抑制至关重要。近年来,与各种表观遗传调控模式相关的研究如雨后春笋般涌现,如 DNA 甲基化、组蛋白尾部翻译后修饰、染色质结构的非编码 RNA 调控和核小体重塑。全基因组表观遗传谱分析和多能干细胞分化的技术进步是阐明发育过程中和核重编程中细胞身份的表观遗传调控的主要驱动力。表观遗传机制不仅以细胞类型特异性的方式调节转录状态,而且还建立了更高阶的基因组拓扑结构和核架构。在这里,我们回顾了多能性的表观遗传调控以及与多能干细胞分化相关的变化。我们重点关注 DNA 甲基化、DNA 去甲基化和常见的组蛋白尾部修饰。最后,我们简要讨论了多能干细胞系中的表观遗传异质性以及表观遗传模式对基因组拓扑结构的影响。

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