Cohesin-mediated interactions organize chromosomal domain architecture.
Cohesin-mediated interactions organize chromosomal domain architecture.
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DOI：
10.1038/emboj.2013.237
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发表时间：
2013-12-11
期刊：
影响因子：
11.4
通讯作者：
Hadjur, Suzana
中科院分区：
文献类型：
--
作者：
Sofueva, Sevil;Yaffe, Eitan;Chan, Wen-Ching;Georgopoulou, Dimitra;Rudan, Matteo Vietri;Mira-Bontenbal, Hegias;Pollard, Steven M.;Schroth, Gary P.;Tanay, Amos;Hadjur, Suzana
为了确保在有限的核空间内进行适当的基因调控，染色体促进了对转录区域的访问，同时将所有其他信息打包。最近的研究表明，染色体被组织成巨碱基规模的结构域，划分活跃和不活跃的遗传元件，这表明区室化对基因组功能很重要。在这里，我们表明，非常具体的远程相互作用锚定的cohesin/CTCF网站，但不是cohesin唯一或CTCF唯一的网站，形成一个层次的染色体环。这些环划分拓扑域并在其中形成复杂的内部结构。有丝分裂后细胞核缺乏功能性粘连蛋白，表现出与粘连蛋白/CTCF接触丢失和拓扑结构域松弛相关的全局结构变化。转录分析表明，这种结构域组织的粘附素依赖的扰动导致广泛的基因失调的粘附素结合和非结合基因。因此，我们的数据支持在全球组织的域结构中的作用，并建议域的功能，以稳定它们内的转录程序。染色体区室化被认为对基因组功能非常重要。高分辨率技术，如Hi-C，ChIP和4C-seq提供了新的见解凝聚在塑造核架构的动态作用。
To ensure proper gene regulation within constrained nuclear space, chromosomes facilitate access to transcribed regions, while compactly packaging all other information. Recent studies revealed that chromosomes are organized into megabase-scale domains that demarcate active and inactive genetic elements, suggesting that compartmentalization is important for genome function. Here, we show that very specific long-range interactions are anchored by cohesin/CTCF sites, but not cohesin-only or CTCF-only sites, to form a hierarchy of chromosomal loops. These loops demarcate topological domains and form intricate internal structures within them. Post-mitotic nuclei deficient for functional cohesin exhibit global architectural changes associated with loss of cohesin/CTCF contacts and relaxation of topological domains. Transcriptional analysis shows that this cohesin-dependent perturbation of domain organization leads to widespread gene deregulation of both cohesin-bound and non-bound genes. Our data thereby support a role for cohesin in the global organization of domain structure and suggest that domains function to stabilize the transcriptional programmes within them. Chromosomal compartmentalization has been recognized as important for genome function. High-resolution techniques such as Hi-C, ChIP- and 4C-seq offer novel insights into cohesin's dynamic role in shaping the nuclear architecture.
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影响因子：
64.5
作者：
Phillips-Cremins JE;Sauria ME;Sanyal A;Gerasimova TI;Lajoie BR;Bell JS;Ong CT;Hookway TA;Guo C;Sun Y;Bland MJ;Wagstaff W;Dalton S;McDevitt TC;Sen R;Dekker J;Taylor J;Corces VG
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Corces VG
粘着素相关染色质相互作用的基因组景观。
影响因子：
7
作者：
DeMare LE;Leng J;Cotney J;Reilly SK;Yin J;Sarro R;Noonan JP
通讯作者：
Noonan JP
粘连蛋白在 T 细胞受体重排和胸腺细胞分化中的作用。
影响因子：
64.8
作者：
Seitan, Vlad C.;Hao, Bingtao;Tachibana-Konwalski, Kikue;Lavagnolli, Thais;Mira-Bontenbal, Hegias;Brown, Karen E.;Teng, Grace;Carroll, Tom;Terry, Anna;Horan, Katie;Marks, Hendrik;Adams, David J.;Schatz, David G.;Aragon, Luis;Fisher, Amanda G.;Krangel, Michael S.;Nasmyth, Kim;Merkenschlager, Matthias
通讯作者：
Merkenschlager, Matthias
影响因子：
9.8
作者：
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影响因子：
64.8
作者：
Shen, Yin;Yue, Feng;McCleary, David F.;Ye, Zhen;Edsall, Lee;Kuan, Samantha;Wagner, Ulrich;Dixon, Jesse;Lee, Leonard;Lobanenkov, Victor V.;Ren, Bing
通讯作者：
Ren, Bing