Chromatin architecture reorganization during stem cell differentiation.
Chromatin architecture reorganization during stem cell differentiation.
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DOI：
10.1038/nature14222
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发表时间：
2015-02-19
期刊：
影响因子：
64.8
通讯作者：
Ren B
中科院分区：
文献类型：
--
作者：
Dixon JR;Jung I;Selvaraj S;Shen Y;Antosiewicz-Bourget JE;Lee AY;Ye Z;Kim A;Rajagopal N;Xie W;Diao Y;Liang J;Zhao H;Lobanenkov VV;Ecker JR;Thomson JA;Ren B
高阶染色质结构正在成为基因表达的重要调节因子。尽管已经在基因组中确定了动态染色质结构，但哺乳动物发育和谱系指定过程中染色质动态的全部范围仍然不清楚。通过绘制人类胚胎干细胞(HESC)和四个hESC衍生谱系的全基因组染色质相互作用图，我们揭示了谱系指定过程中广泛的染色质重组。我们观察到，虽然拓扑域的边界在分化过程中保持不变，但域内和域间的相互作用都发生了巨大的变化，改变了整个基因组中36%的活跃和不活跃的染色体“间隔”。通过将染色质相互作用图与单倍型解析的表观基因组和转录组数据集相结合，我们发现基因表达中普遍存在的等位基因偏见与连锁启动子和远端增强子的染色质状态相关。因此，我们的结果提供了染色质动力学的全球视角，并为研究不同人类细胞系中基因表达的远程控制提供了资源。
Higher order chromatin structure is emerging as an important regulator of gene expression. Although dynamic chromatin structures have been identified in the genome, the full scope of chromatin dynamics during mammalian development and lineage specification remains obscure. By mapping genome-wide chromatin interactions in human embryonic stem cells (hESC) and four hESC-derived lineages, we uncover extensive chromatin reorganization during lineage specification. We observe that while topological domain boundaries remain intact during differentiation, interactions both within and between domains change dramatically, altering 36% of active and inactive chromosomal “compartments” throughout the genome. By integrating chromatin interaction maps with haplotype-resolved epigenome and transcriptome datasets, we find widespread allelic bias in gene expression correlated with allele-biased chromatin states of linked promoters and distal enhancers. Our results therefore provide a global view of chromatin dynamics and a resource for studying long-range control of gene expression in distinct human cell lineages.