Histone exchange chromatin dynamics and chromatin function: Role of ATP-dependent chromatin remodelling factor Fun30 in epigenetics

组蛋白交换染色质动力学和染色质功能：ATP 依赖性染色质重塑因子 Fun30 在表观遗传学中的作用

• 批准号: BB/F020236/1
• 负责人: Patrick Varga-Weisz
• 金额: $ 40.65万
• 依托单位: Babraham Institute
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF020236%2F1
• 关键词: Histone; exchange; chromatin; dynamics; function

The genetic material in each cell is packaged and organized by an extremely complex, heterogeneous structure, called chromatin. The basic building block of this structure is the nucleosome, a molecular protein spool around which DNA winds in almost two turns. Nucleosomes are modified and interact with other proteins to create chromatin structures that shut down genes or allow access to the machinery that read out the information from genes. Specific chromatin structures mediate gene regulation and are required for genome stability and chromosome segregation. Such structures have to be faithfully duplicated for the maintenance of gene expression patterns through development. Defects in heterochromatin have been linked to genome instability, infertility, accelerated aging and an enhanced risk of cancer. Despite this fundamental importance, our knowledge of how specific chromatin structures, such as heterochromatin, are assembled and maintained is limited. We will study how nucleosome remodelling and modification enzymes interact to assemble a specific chromatin structure to shut down genes and to stabilise the genome. This research has implications for our understanding of normal development, but also for cancer and fertility.

每个细胞中的遗传物质由一种极其复杂的异质结构（染色质）包装和组织起来。这种结构的基本组成部分是核小体，一种分子蛋白质线轴，DNA绕其缠绕近两圈。核小体被修饰并与其他蛋白质相互作用以产生染色质结构，从而关闭基因或允许进入从基因读取信息的机器。特定的染色质结构介导基因调控，并且是基因组稳定性和染色体分离所必需的。这种结构必须忠实地复制，以维持基因表达模式，通过发展。异染色质缺陷与基因组不稳定、不育、加速衰老和癌症风险增加有关。尽管这一基本的重要性，我们的知识如何特定的染色质结构，如异染色质，组装和维护是有限的。我们将研究核小体重塑和修饰酶如何相互作用以组装特定的染色质结构来关闭基因并稳定基因组。这项研究对我们理解正常发育，以及癌症和生育能力都有意义。

项目成果

SWI/SNF-like chromatin remodeling factor Fun30 supports point centromere function in S. cerevisiae.

• DOI: 10.1371/journal.pgen.1002974
• 发表时间: 2012-09
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Durand-Dubief M;Will WR;Petrini E;Theodorou D;Harris RR;Crawford MR;Paszkiewicz K;Krueger F;Correra RM;Vetter AT;Miller JR;Kent NA;Varga-Weisz P
• 通讯作者: Varga-Weisz P

Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.

• DOI: 10.1038/s41467-017-02651-5
• 发表时间: 2018-01-09
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Fellows R;Denizot J;Stellato C;Cuomo A;Jain P;Stoyanova E;Balázsi S;Hajnády Z;Liebert A;Kazakevych J;Blackburn H;Corrêa RO;Fachi JL;Sato FT;Ribeiro WR;Ferreira CM;Perée H;Spagnuolo M;Mattiuz R;Matolcsi C;Guedes J;Clark J;Veldhoen M;Bonaldi T;Vinolo MAR;Varga-Weisz P
• 通讯作者: Varga-Weisz P

In vitro Enzymatic Assays of Histone Decrotonylation on Recombinant Histones.

• DOI: 10.21769/bioprotoc.2924
• 发表时间: 2018-07
• 期刊: Bio-protocol
• 影响因子: 0.8
• 作者: R. Fellows;P. Varga-Weisz

Keeping chromatin quiet: how nucleosome remodeling restores heterochromatin after replication.

保持染色质安静：核小体重塑如何在复制后恢复异染色质。

• DOI: 10.4161/cc.10.23.18558
• 发表时间: 2011
• 期刊: Cell cycle (Georgetown, Tex.)
• 作者: Mermoud JE