Transcription-dependent cohesin repositioning rewires chromatin loops in cellular senescence.
Transcription-dependent cohesin repositioning rewires chromatin loops in cellular senescence.
复制标题
转录依赖的粘附蛋白重新定位在细胞衰老中改变染色质环。
DOI：
10.1038/s41467-020-19878-4
复制
发表时间：
2020-11-27
影响因子：
16.6
通讯作者：
Narita M
中科院分区：
文献类型：
--
作者：
Olan I;Parry AJ;Schoenfelder S;Narita M;Ito Y;Chan ASL;Slater GSC;Bihary D;Bando M;Shirahige K;Kimura H;Samarajiwa SA;Fraser P;Narita M
衰老是一种稳定的增殖停滞状态，通常伴随着衰老相关的分泌表型，其调节组织稳态。由染色质环促进的增强子-启动子相互作用在基因调控中起关键作用，但它们在衰老中的相关性仍然难以捉摸。在这里，我们使用Hi-C显示致癌RAS诱导的人二倍体成纤维细胞衰老伴随着广泛的增强子-启动子重新布线，这与动态粘附素结合基因组密切相关。我们发现从头cohesin峰往往在3 '端的一个子集的活性基因。RAS诱导的从头粘附素峰是转录依赖性的，并且富集衰老相关基因，例如IL 1B，其中从头粘附素结合参与新环形成。在终末分化的巨噬细胞中观察到类似的IL 1B诱导，伴有从头粘连蛋白出现和新环形成，但在TNFα处理的细胞中未观察到。这些结果表明，RAS诱导的衰老代表了细胞命运决定样过程，其特征在于独特的基因表达谱和3D基因组折叠签名，部分通过染色质上的粘着蛋白再分布介导。衰老是一种稳定的增殖停滞状态。在这里，作者对致癌RAS诱导的人成纤维细胞衰老进行了Hi-C分析，并描述了与衰老特异性基因表达谱相关的3D基因组折叠的变化，这些变化部分通过染色质上的粘着蛋白再分布介导。
Senescence is a state of stable proliferative arrest, generally accompanied by the senescence-associated secretory phenotype, which modulates tissue homeostasis. Enhancer-promoter interactions, facilitated by chromatin loops, play a key role in gene regulation but their relevance in senescence remains elusive. Here, we use Hi-C to show that oncogenic RAS-induced senescence in human diploid fibroblasts is accompanied by extensive enhancer-promoter rewiring, which is closely connected with dynamic cohesin binding to the genome. We find de novo cohesin peaks often at the 3′ end of a subset of active genes. RAS-induced de novo cohesin peaks are transcription-dependent and enriched for senescence-associated genes, exemplified by IL1B, where de novo cohesin binding is involved in new loop formation. Similar IL1B induction with de novo cohesin appearance and new loop formation are observed in terminally differentiated macrophages, but not TNFα-treated cells. These results suggest that RAS-induced senescence represents a cell fate determination-like process characterised by a unique gene expression profile and 3D genome folding signature, mediated in part through cohesin redistribution on chromatin. Senescence is a state of stable proliferative arrest. Here, the authors perform Hi-C analysis on oncogenic RAS-induced senescence in human fibroblasts and characterize the changes in the 3D genome folding associated with the senescence-specific gene expression profile, which are mediated in part through cohesin redistribution on chromatin.
登录
查看更多内容
影响因子：
16
作者：
Chandra, Tamir;Kirschner, Kristina;Thuret, Jean-Yves;Pope, Benjamin D.;Ryba, Tyrone;Newman, Scott;Ahmed, Kashif;Samarajiwa, Shamith A.;Salama, Rafik;Carroll, Thomas;Stark, Rory;Janky, Rekin's;Narita, Masako;Xue, Lixiang;Chicas, Agustin;Nunez, Sabrina;Janknecht, Ralf;Hayashi-Takanaka, Yoko;Wilson, Michael D.;Marshall, Aileen;Odom, Duncan T.;Babu, M. Madan;Bazett-Jones, David P.;Tavare, Simon;Edwards, Paul A. W.;Lowe, Scott W.;Kimura, Hiroshi;Gilbert, David M.;Narita, Masashi
通讯作者：
Narita, Masashi
影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
影响因子：
64.8
作者：
Jin, Fulai;Li, Yan;Dixon, Jesse R.;Selvaraj, Siddarth;Ye, Zhen;Lee, Ah Young;Yen, Chia-An;Schmitt, Anthony D.;Espinoza, Celso A.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
7
作者：
Heidari N;Phanstiel DH;He C;Grubert F;Jahanbani F;Kasowski M;Zhang MQ;Snyder MP
通讯作者：
Snyder MP
影响因子：
9.8
作者：
Glynn, EF;Megee, PC;Gerton, JL
通讯作者：
Gerton, JL