Mesoscale modeling reveals formation of an epigenetically driven HOXC gene hub
Mesoscale modeling reveals formation of an epigenetically driven HOXC gene hub
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DOI：
10.1073/pnas.1816424116
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发表时间：
2019-03-12
影响因子：
11.1
通讯作者：
Schlick, Tamar
中科院分区：
文献类型：
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作者：
Bascom, Gavin D.;Myers, Christopher G.;Schlick, Tamar
基因表达在结构水平上通过核小体定位、组蛋白尾部乙酰化和连接体组蛋白（LH）结合来协调。在这里，我们整合了现有的数据，核小体定位，核小体自由区（NFR），乙酰化岛，LH结合位点的“折叠”在硅片上的55 kb HOXC基因簇，并调查基因的折叠每个功能的作用。基因簇自发地形成动态连接枢纽，其特征在于分层环，其同时容纳多个接触，并将启动子之间的平均距离减少约100 nm。接触概率矩阵显示“条纹”附近的启动子区域，与转录调控的功能。有趣的是，虽然LH蛋白单独减少长距离接触和乙酰化单独增加短暂的接触，结合LH和乙酰化产生长距离接触。因此，我们的工作强调染色质结构是如何通过表观遗传因素协调的，并为核小体解析模型结合表观遗传修饰来理解和预测基因活性开辟了道路。
Gene expression is orchestrated at the structural level by nucleosome positioning, histone tail acetylation, and linker histone (LH) binding. Here, we integrate available data on nucleosome positioning, nucleosome-free regions (NFRs), acetylation islands, and LH binding sites to "fold" in silico the 55-kb HOXC gene cluster and investigate the role of each feature on the gene's folding. The gene cluster spontaneously forms a dynamic connection hub, characterized by hierarchical loops which accommodate multiple contacts simultaneously and decrease the average distance between promoters by similar to 100 nm. Contact probability matrices exhibit "stripes" near promoter regions, a feature associated with transcriptional regulation. Interestingly, while LH proteins alone decrease long-range contacts and acetylation alone increases transient contacts, combined LH and acetylation produce long-range contacts. Thus, our work emphasizes how chromatin architecture is coordinated strongly by epigenetic factors and opens the way for nucleosome resolution models incorporating epigenetic modifications to understand and predict gene activity.