Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments.
Cohesin-based chromatin interactions enable regulated gene expression within preexisting architectural compartments.
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DOI：
10.1101/gr.161620.113
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发表时间：
2013-12
期刊：
影响因子：
7
通讯作者：
Merkenschlager M
中科院分区：
文献类型：
--
作者：
Seitan VC;Faure AJ;Zhan Y;McCord RP;Lajoie BR;Ing-Simmons E;Lenhard B;Giorgetti L;Heard E;Fisher AG;Flicek P;Dekker J;Merkenschlager M
染色体构象捕获方法表明，间期染色质被划分为空间隔离的 Mb 大小的区室和亚 Mb 大小的拓扑域。这种划分被认为有助于基因和调控元件的匹配，但其精确的功能和机制基础仍然未知。粘连蛋白控制染色体拓扑，以实现循环细胞中的 DNA 修复和染色体分离。此外，粘连蛋白与活性增强子和启动子以及 CTCF 结合，形成对基因调控重要的长程相互作用。尽管这些发现表明粘连蛋白在基因组组织中发挥着重要作用，但这种作用尚未在全球范围内进行评估。出乎意料的是，我们发现在体内粘连蛋白基因耗尽后，非循环小鼠胸腺细胞中仍保留了结构区室。然而，粘连蛋白调节基因所在的区室内的特定长程相互作用需要粘连蛋白。粘连蛋白耗竭减少了粘连蛋白结合位点之间的相互作用，而与转录激活和抑制相关的染色质特征之间的替代相互作用变得更加突出，并伴随着基因表达的相应变化。我们的研究结果表明，粘连蛋白介导的长程相互作用促进了预先存在的染色体区室中离散的基因表达状态。
Chromosome conformation capture approaches have shown that interphase chromatin is partitioned into spatially segregated Mb-sized compartments and sub-Mb-sized topological domains. This compartmentalization is thought to facilitate the matching of genes and regulatory elements, but its precise function and mechanistic basis remain unknown. Cohesin controls chromosome topology to enable DNA repair and chromosome segregation in cycling cells. In addition, cohesin associates with active enhancers and promoters and with CTCF to form long-range interactions important for gene regulation. Although these findings suggest an important role for cohesin in genome organization, this role has not been assessed on a global scale. Unexpectedly, we find that architectural compartments are maintained in noncycling mouse thymocytes after genetic depletion of cohesin in vivo. Cohesin was, however, required for specific long-range interactions within compartments where cohesin-regulated genes reside. Cohesin depletion diminished interactions between cohesin-bound sites, whereas alternative interactions between chromatin features associated with transcriptional activation and repression became more prominent, with corresponding changes in gene expression. Our findings indicate that cohesin-mediated long-range interactions facilitate discrete gene expression states within preexisting chromosomal compartments.
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影响因子：
14.9
作者：
Flicek P;Ahmed I;Amode MR;Barrell D;Beal K;Brent S;Carvalho-Silva D;Clapham P;Coates G;Fairley S;Fitzgerald S;Gil L;García-Girón C;Gordon L;Hourlier T;Hunt S;Juettemann T;Kähäri AK;Keenan S;Komorowska M;Kulesha E;Longden I;Maurel T;McLaren WM;Muffato M;Nag R;Overduin B;Pignatelli M;Pritchard B;Pritchard E;Riat HS;Ritchie GR;Ruffier M;Schuster M;Sheppard D;Sobral D;Taylor K;Thormann A;Trevanion S;White S;Wilder SP;Aken BL;Birney E;Cunningham F;Dunham I;Harrow J;Herrero J;Hubbard TJ;Johnson N;Kinsella R;Parker A;Spudich G;Yates A;Zadissa A;Searle SM
通讯作者：
Searle SM
影响因子：
9.2
作者：
Gerlich, Daniel;Koch, Birgit;Ellenberg, Jan
通讯作者：
Ellenberg, Jan
影响因子：
7
作者：
Cuddapah, Suresh;Jothi, Raja;Zhao, Keji
通讯作者：
Zhao, Keji
影响因子：
64.8
作者：
Guelen, Lars;Pagie, Ludo;van Steensel, Bas
通讯作者：
van Steensel, Bas
CTCF结合元件介导V（d）J重组的控制。
影响因子：
64.8
作者：
Guo, Chunguang;Yoon, Hye Suk;Franklin, Andrew;Jain, Suvi;Ebert, Anja;Cheng, Hwei-Ling;Hansen, Erica;Despo, Orion;Bossen, Claudia;Vettermann, Christian;Bates, Jamie G.;Richards, Nicholas;Myers, Darienne;Patel, Harin;Gallagher, Michael;Schlissel, Mark S.;Murre, Cornelis;Busslinger, Meinrad;Giallourakis, Cosmas C.;Alt, Frederick W.
通讯作者：
Alt, Frederick W.