Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells.
复制标题
DOI：
10.1093/jmcb/mjv060
复制
发表时间：
2016-08
影响因子：
5.5
通讯作者：
Khochbin S
中科院分区：
文献类型：
--
作者：
Morozumi Y;Boussouar F;Tan M;Chaikuad A;Jamshidikia M;Colak G;He H;Nie L;Petosa C;de Dieuleveult M;Curtet S;Vitte AL;Rabatel C;Debernardi A;Cosset FL;Verhoeyen E;Emadali A;Schweifer N;Gianni D;Gut M;Guardiola P;Rousseaux S;Gérard M;Knapp S;Zhao Y;Khochbin S
尽管保守的AAA atp酶和溴结构域因子ATAD2已被描述为在许多癌症中上调的转录共激活因子，但其功能仍然知之甚少。在胚胎干细胞中，我们使用ChIP-seq、chip -蛋白质组学和RNA-seq实验，发现Atad2是一种丰富的核小体结合蛋白，存在于活性基因上，与染色质重塑、DNA复制和DNA修复因子相关。对其溴结构域的结构分析和随后的研究表明，组蛋白乙酰化引导ATAD2到达染色质，导致染色质可及性和组蛋白动力学的总体增加，这是基因组高表达基因部分适当活性所必需的。虽然在呈指数增长的细胞中，Atad2对于细胞生长似乎是必不可少的，但在分化的ES细胞中，Atad2对于维持特定的基因表达程序、控制增殖和分化至关重要。总之，这项工作将Atad2定义为一般染色质模板活动（如转录）的促进剂。
Although the conserved AAA ATPase and bromodomain factor, ATAD2, has been described as a transcriptional co-activator upregulated in many cancers, its function remains poorly understood. Here, using a combination of ChIP-seq, ChIP-proteomics, and RNA-seq experiments in embryonic stem cells where Atad2 is normally highly expressed, we found that Atad2 is an abundant nucleosome-bound protein present on active genes, associated with chromatin remodelling, DNA replication, and DNA repair factors. A structural analysis of its bromodomain and subsequent investigations demonstrate that histone acetylation guides ATAD2 to chromatin, resulting in an overall increase of chromatin accessibility and histone dynamics, which is required for the proper activity of the highly expressed gene fraction of the genome. While in exponentially growing cells Atad2 appears dispensable for cell growth, in differentiating ES cells Atad2 becomes critical in sustaining specific gene expression programmes, controlling proliferation and differentiation. Altogether, this work defines Atad2 as a facilitator of general chromatin-templated activities such as transcription.