Architectural protein subclasses shape 3D organization of genomes during lineage commitment.
Architectural protein subclasses shape 3D organization of genomes during lineage commitment.
复制标题
DOI：
10.1016/j.cell.2013.04.053
复制
发表时间：
2013-06-06
期刊：
影响因子：
64.5
通讯作者：
Corces VG
中科院分区：
文献类型：
--
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
了解染色质的拓扑结构可能会揭示基因组和表观基因组如何在发育过程中共同控制细胞命运的有价值的见解。在这里，我们生成了胚胎干细胞和神经祖细胞中七个基因组位点的高分辨率结构图。我们观察到一个层次的3-D的相互作用，在分化过程中进行显着的重组在亚Mb规模。CTCF，调解人，和cohesin的不同组合显示出广泛的丰富循环的相互作用，在不同的长度尺度。CTCF/粘附素锚长程组成性相互作用，形成不变子域的拓扑基础。相反，介体/粘附素与先锋因子一起桥接较大亚结构域内和之间的短程增强子-启动子相互作用。在ES细胞中Smc 1或Med 12的敲低导致空间结构的破坏和在粘附素介导的相互作用中发现的基因的下调。我们的结论是，细胞类型特异性染色质组织发生在亚Mb规模和建筑蛋白质形状的基因组在层次长度尺度。
Understanding the topological configurations of chromatin may reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3-D interactions that undergo marked reorganization at the sub-Mb scale during differentiation. Distinct combinations of CTCF, Mediator, and cohesin show widespread enrichment in looping interactions at different length scales. CTCF/cohesin anchor long-range constitutive interactions that form the topological basis for invariant sub-domains. Conversely, Mediator/cohesin together with pioneer factors bridge shortrange enhancer-promoter interactions within and between larger sub-domains. Knockdown of Smc1 or Med12 in ES cells results in disruption of spatial architecture and down-regulation of genes found in cohesin-mediated interactions. We conclude that cell type-specific chromatin organization occurs at the sub-Mb scale and that architectural proteins shape the genome in hierarchical length scales.
登录
查看更多内容
影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
64.5
作者：
Guo C;Gerasimova T;Hao H;Ivanova I;Chakraborty T;Selimyan R;Oltz EM;Sen R
通讯作者：
Sen R
影响因子：
16
作者：
Hou, Chunhui;Li, Li;Qin, Zhaohui S.;Corces, Victor G.
通讯作者：
Corces, Victor G.
影响因子：
64.8
作者：
Hadjur, Suzana;Williams, Luke M.;Ryan, Natalie K.;Cobb, Bradley S.;Sexton, Tom;Fraser, Peter;Fisher, Amanda G.;Merkenschlager, Matthias
通讯作者：
Merkenschlager, Matthias
影响因子：
64.8
作者：
通讯作者：
--