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Characterization of chromatin dynamics in cycling cells

循环细胞中染色质动力学的表征

基本信息

批准号：
1785999
负责人：
金额：
--
依托单位：
University of Dundee
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1785999
关键词：
Characterization chromatin dynamics cycling cells

项目摘要

Epigenetic information relies on a combination of DNA modifications, nucleosome positioning, histone modifications, histone variants, chromatin remodellers, higher-order structures and many proteins that define, maintain and functionally translate this information. During lineage propagation, cells must duplicate their genetic and epigenetic information to maintain cell identity. Yet, the mechanisms underlying the maintenance of epigenetic information in cycling cells remain largely unknown. In S phase, the DNA replication machinery provokes genome-wide disruption of chromatin structure, and thus challenges the persistence of epigenetic information (1). Nucleosomes are evicted ahead of the replisome and reassembled within minutes on newly replicated DNA by the recycling of parental histones and the deposition of newly synthesized histones (2). However, several aspects of histone-based information are not restored so quickly, revealing that restoration of epigenetic information is not necessarily tightly coupled to DNA replication. For example, H3K27me3, which is required for gene repression, is restored in the following G1 phase (2). These chromatin components, which are instrumental for cell identity, are often found deregulated in cancer or intellectual disabilities linked to nervous system development (1). Therefore it is crucial to understand the mechanisms that underlie the faithful restoration of epigenetic information.Project provides training in Interdisciplinary Skills.

表观遗传信息依赖于DNA修饰、核小体定位、组蛋白修饰、组蛋白变体、染色质重塑剂、高级结构以及许多定义、维持和功能性翻译该信息的蛋白质的组合。在谱系繁殖期间，细胞必须复制其遗传和表观遗传信息以维持细胞身份。然而，在循环细胞中维持表观遗传信息的潜在机制在很大程度上仍然未知。在S期，DNA复制机制引起染色质结构的全基因组破坏，从而挑战表观遗传信息的持久性（1）。核小体在复制体之前被驱逐，并在几分钟内通过亲本组蛋白的再循环和新合成的组蛋白的沉积在新复制的DNA上重新组装（2）。然而，基于组蛋白的信息的几个方面并没有如此迅速地恢复，这表明表观遗传信息的恢复不一定与DNA复制紧密相关。例如，基因阻遏所需的H3K27me3在随后的G1期恢复（2）。这些染色质成分，这是细胞身份的工具，经常被发现在癌症或与神经系统发育相关的智力残疾中失调（1）。因此，了解表观遗传信息忠实恢复的机制至关重要。项目提供跨学科技能培训。