REGULATION OF 3-D CHROMATIN ARCHITECTURE OF EMBRYONIC STEM CELLS

胚胎干细胞 3-D 染色质结构的调控

• 批准号: 8362740
• 负责人: BARBARA PANNING
• 金额: $ 2.94万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362740
• 关键词: 3-Dimensional; Architecture; Cells; Chromatin; Chromatin Structure; Complex; DNA Methylation; Funding; Genes; Grant; Higher Order Chromatin Structure; Maps; Molecular; National Center for Research Resources; Play; Polycomb; Principal Investigator; Regulation; Research; Research Infrastructure; Resources; Role; Somatic Cell; Source; System; United States National Institutes of Health; Work; X-Ray Tomography; cell type; cost; embryonic stem cell; genetic regulatory protein; genome-wide; histone modification; pluripotency; promoter; self-renewal; stem cell therapy

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.

该子项目是利用资源的众多研究子项目之一 由 NIH/NCRR 资助的中心拨款提供。子项目的主要支持 并且子项目的主要研究者可能是由其他来源提供的， 包括其他 NIH 来源。 子项目可能列出的总成本 代表子项目使用的中心基础设施的估计数量， NCRR 赠款不直接向子项目或子项目工作人员提供资金。 胚胎干细胞（ESC）提供了一个实验上易于处理的系统来研究 染色质结构的发育调节改变。 ESC 被视为 干细胞治疗的潜在材料来源，因为它们具有多能性，或者具有分化成所有细胞类型的能力，并且可以在多能状态下无限期生长[14]。然而，控制自我更新和多能性的分子机制尚不清楚。许多实验室（包括我们自己的实验室）的工作表明，染色质调节蛋白在 ESC 自我更新和多能性中发挥着重要作用。 ESC 的特点是高阶染色质结构通常是动态的 并允许转录机制。 DNA 全基因组图谱 甲基化谱和翻译后组蛋白修饰表明 特殊的染色质状态表征了 ESC 中活性、抑制和潜在活性基因的启动子。此外，相同的染色质调节复合物在 ESC 中的作用与在体细胞中的作用截然不同。在某些情况下，体细胞中必需的复合物在 ESC 中是可有可无的：多梳抑制复合物 (PRC) 提供了这样的例子。