REGULATION OF 3-D CHROMATIN ARCHITECTURE OF EMBRYONIC STEM CELLS

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 胚胎干细胞(ESCs)为研究提供了一种实验上易于操作的系统 染色质结构的发育调节变化。ESCs被视为一种 干细胞治疗的潜在材料来源，因为它们是多能性的，或者具有分化为所有细胞类型的能力，并且可以在多能性状态下无限生长[14]。然而，控制自我更新和多能性的分子机制还不是很清楚。包括我们自己在内的许多实验室的研究表明，染色质调节蛋白在ESC的自我更新和多能性中发挥着重要作用。 ESCs的特征是高阶染色质结构，通常是动态的 以及对转录机器的许可。DNA的全基因组作图 甲基化图谱和翻译后组蛋白修饰显示 特殊的染色质状态表征了ESCs中活性、抑制和潜在活性基因的启动子。此外，同一染色质调节复合体在胚胎干细胞中的作用与在体细胞中的作用非常不同。在某些情况下，在体细胞中必不可少的复合体在ESCs中是可有可无的：多梳抑制复合体(PRCs)就是一个例子。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Embryonic stem cells (ESCs) provide an experimentally tractable system to study developmentally regulated alterations in chromatin structure. ESCs are regarded as a potential source of material for stem cell therapies because they are pluripotent, or have the ability to differentiate into all cell types, and can grow indefinitely in the pluripotent state[14]. However, the molecular mechanisms governing self-renewal and pluripotency are not well understood. Work from many labs, including our own, shows that chromatin regulatory proteins play an important role in ESC self-renewal and pluripotency. ESCs are characterized by higher order chromatin structure that is generally dynamic and permissive to the transcriptional machinery. Genome-wide mapping of DNA methylation profiles and of post-translational histone modifications showed that specialized chromatin states characterize promoters of active, repressed and potentially active genes in ESCs. In addition, the same chromatin regulatory complex can have a very different role in ESCs than in somatic cells. In some instances, complexes that are essential in somatic cells are dispensable in ESCs: the Polycomb Repressive Complexes (PRCs) provide such an example.