Large-scale functional organization of long-range chromatin interaction networks.
Large-scale functional organization of long-range chromatin interaction networks.
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DOI：
10.1016/j.celrep.2012.09.022
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发表时间：
2012-11-29
期刊：
影响因子：
8.8
通讯作者：
Ruan Y
中科院分区：
文献类型：
--
作者：
Sandhu KS;Li G;Poh HM;Quek YL;Sia YY;Peh SQ;Mulawadi FH;Lim J;Sikic M;Menghi F;Thalamuthu A;Sung WK;Ruan X;Fullwood MJ;Liu E;Csermely P;Ruan Y
染色质相互作用在转录调控中起着重要作用。为了更好地理解这些相互作用的潜在进化和功能限制，我们实施了一种系统方法来检查人类细胞中RNA聚合酶- ii相关染色质相互作用。我们发现，参与染色质相互作用的总基因组元件中有40%汇集成一个巨大的、无标度的、分层的网络，组织成染色质群落。这些群落在进化过程中具有丰富的特定功能和合成器。来自全基因组关联研究的疾病相关snp在相互作用较少的节点中富集，这意味着它们通过限制相互作用的总数来选择有害的相互作用，我们使用体细胞和种系癌症突变数据进一步验证了这一模型。这些集线器缺乏与疾病相关的snp，构成了关键细胞功能的非随机互联核心，并在小鼠突变体中表现出致命性，这支持了一种进化选择，这种选择有利于最不进化的关键基因组域的非随机空间聚类，而不是基因组中的随机遗传或转录错误。总之，我们的分析揭示了一个系统级的进化框架，它在三个维度上塑造了人类基因组功能分区和容错的转录调控。
Chromatin interactions play important roles in transcription regulation. To better understand the underlying evolutionary and functional constraints of these interactions, we implemented a systems approach to examine RNA polymerase-II-associated chromatin interactions in human cells. We found that 40% of the total genomic elements involved in chromatin interactions converged to a giant, scale-free-like, hierarchical network organized into chromatin communities. The communities were enriched in specific functions and were syntenic through evolution. Disease-associated SNPs from genome-wide association studies were enriched among the nodes with fewer interactions, implying their selection against deleterious interactions by limiting the total number of interactions, a model that we further reconciled using somatic and germline cancer mutation data. The hubs lacked disease-associated SNPs, constituted a nonrandomly interconnected core of key cellular functions, and exhibited lethality in mouse mutants, supporting an evolutionary selection that favored the nonrandom spatial clustering of the least-evolving key genomic domains against random genetic or transcriptional errors in the genome. Altogether, our analyses reveal a systems-level evolutionary framework that shapes functionally compartmentalized and error-tolerant transcriptional regulation of human genome in three dimensions.
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影响因子：
64.8
作者：
Ernst, Jason;Kheradpour, Pouya;Mikkelsen, Tarjei S.;Shoresh, Noam;Ward, Lucas D.;Epstein, Charles B.;Zhang, Xiaolan;Wang, Li;Issner, Robbyn;Coyne, Michael;Ku, Manching;Durham, Timothy;Kellis, Manolis;Bernstein, Bradley E.
通讯作者：
Bernstein, Bradley E.
影响因子：
12.3
作者：
Li G;Fullwood MJ;Xu H;Mulawadi FH;Velkov S;Vega V;Ariyaratne PN;Mohamed YB;Ooi HS;Tennakoon C;Wei CL;Ruan Y;Sung WK
通讯作者：
Sung WK
DOI：
10.1038/nrc1299
发表时间：
2004-03
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Hah N;Danko CG;Core L;Waterfall JJ;Siepel A;Lis JT;Kraus WL
通讯作者：
Kraus WL
DOI：
10.1073/pnas.0910668107
发表时间：
2010-05-25
影响因子：
11.1
作者：
Ahmadiyeh, Nasim;Pomerantz, Mark M.;Freedman, Matthew L.
通讯作者：
Freedman, Matthew L.