Topological domains in mammalian genomes identified by analysis of chromatin interactions.
Topological domains in mammalian genomes identified by analysis of chromatin interactions.
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DOI：
10.1038/nature11082
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发表时间：
2012-04-11
期刊：
影响因子：
64.8
通讯作者：
Ren, Bing
中科院分区：
文献类型：
--
作者：
Dixon, Jesse R.;Selvaraj, Siddarth;Yue, Feng;Kim, Audrey;Li, Yan;Shen, Yin;Hu, Ming;Liu, Jun S.;Ren, Bing
基因组的空间组织与其生物学功能密切相关，但我们对更高层次的基因组结构的理解是粗糙的，分散的和不完整的。在真核细胞的细胞核中，间期染色体占据不同的染色体区域（CT），并且已经提出了许多关于染色体如何在CT内折叠的模型。然而，这些模型只提供了一些关于高阶染色质结构和基因组功能之间关系的机制细节。基因组技术的最新进展导致了3D基因组组织研究的快速革命。特别是，Hi-C已被引入作为识别全基因组高级染色质相互作用的方法。在本研究中，我们以前所未有的分辨率研究了胚胎干细胞和终末分化细胞类型中人类和小鼠基因组的3D组织。我们确定大，兆碱基大小的本地染色质相互作用域，我们称之为“拓扑结构域”，作为一个普遍的结构特征的基因组组织。这些结构域与限制异染色质扩散的基因组区域相关。这些结构域在不同的细胞类型中是稳定的，并且在物种中高度保守，这表明拓扑结构域是哺乳动物基因组的固有特性。最后，我们发现，拓扑结构域的边界是丰富的绝缘子结合蛋白CTCF，管家基因，tRNA，和SINE反转录转座子，这表明这些因素可能在建立基因组的拓扑结构域结构中发挥作用。
The spatial organization of the genome is intimately linked to its biological function, yet our understanding of higher order genomic structure is coarse, fragmented and incomplete. In the nucleus of eukaryotic cells, interphase chromosomes occupy distinct chromosome territories (CT), and numerous models have been proposed for how chromosomes fold within CTs. These models, however, provide only few mechanistic details about the relationship between higher order chromatin structure and genome function. Recent advances in genomic technologies have led to rapid revolutions in the study of 3D genome organization. In particular, Hi-C has been introduced as a method for identifying higher order chromatin interactions genome wide. In the present study, we investigated the 3D organization of the human and mouse genomes in embryonic stem cells and terminally differentiated cell types at unprecedented resolution. We identify large, megabase-sized local chromatin interaction domains, which we term “topological domains”, as a pervasive structural feature of the genome organization. These domains correlate with regions of the genome that constrain the spread of heterochromatin. The domains are stable across different cell types and highly conserved across species, suggesting that topological domains are an inherent property of mammalian genomes. Lastly, we find that the boundaries of topological domains are enriched for the insulator binding protein CTCF, housekeeping genes, tRNAs, and SINE retrotransposons, suggesting that these factors may play a role in establishing the topological domain structure of the genome.
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影响因子：
64.5
作者：
Xie W;Barr CL;Kim A;Yue F;Lee AY;Eubanks J;Dempster EL;Ren B
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.1018279108
发表时间：
2011-05-03
影响因子：
11.1
作者：
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通讯作者：
Kim, Tae Hoon
影响因子：
64.8
作者：
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通讯作者：
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