Heterochromatin formation in X-inactivation

X 失活过程中异染色质的形成

• 批准号: 7111190
• 负责人: Yifan Liu
• 金额: $ 4.88万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7111190
• 关键词: RNA; binding proteins; cell line; cytogenetics; epigenetics; gene expression; heterochromatin; histones; intermolecular interaction; laboratory rabbit; predoctoral investigator; protein structure function; sex chromosomes; transcription factor

DESCRIPTION (provided by applicant): Recent development in the field of pericentromeric heterochromatin formation and X-inactivation revealed some striking similarities between the two processes. X-inactivation in mammalian female embryonic stem cells can be regarded a developmentally regulated facultative heterochromatin formation process. The long- range goal of this project is to contribute to the understanding of Xist RNA initiated selective repression of inactive X chromosome. Specific aims are to: 1) identify and study the effector proteins that interact with Xi- specific histone modifications, and 2) elucidate the mechanism by which Xist RNA recruit Ezh2 and possible other HMTs to participate in X inactivation. A series of biochemical, biophysical, immunocytological, and cell biological approaches have been proposed, first to examine Cbx proteins for possible interactions with histone modifications and RNAs, then to expand to more potential candidates and eventually perform unbiased screen for more key players in X-inactivation process. The proposed research will not only further our understanding of roles played by heterochromatin as a widely-used epigenetic regulator, but also provide insights into an important aspect of early embryonic development and embryonic stem cell differentiation.

描述（由申请人提供）：在近着丝粒异染色质形成和X-失活领域的最新进展揭示了这两个过程之间的一些惊人的相似性。哺乳动物雌性胚胎干细胞中的X-失活可以被认为是发育调节的兼性异染色质形成过程。该项目的长期目标是有助于理解Xist RNA启动的对失活X染色体的选择性抑制。具体目标是：1）鉴定和研究与Xi特异性组蛋白修饰相互作用的效应蛋白，和2）阐明Xist RNA募集Ezh 2和可能的其他HMT参与X失活的机制。一系列生物化学、生物物理学、免疫细胞学和细胞生物学方法已经被提出，首先检测Cbx蛋白与组蛋白修饰和RNA的可能相互作用，然后扩展到更多潜在的候选者，并最终对X失活过程中的更多关键参与者进行无偏筛选。这项研究不仅将进一步加深我们对异染色质作为广泛使用的表观遗传调节因子所起作用的理解，而且还将为早期胚胎发育和胚胎干细胞分化的一个重要方面提供见解。