Regulatory elements can be essential for maintaining broad chromatin organization and cell viability.
Regulatory elements can be essential for maintaining broad chromatin organization and cell viability.
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DOI：
10.1093/nar/gkac197
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发表时间：
2022-05-06
影响因子：
14.9
通讯作者：
Wei, Wensheng
中科院分区：
文献类型：
--
作者：
Liu, Ying;Ding, Bo;Zheng, Lina;Xu, Ping;Liu, Zhiheng;Chen, Zhao;Wu, Peiyao;Zhao, Ying;Pan, Qian;Guo, Yu;Wang, Wei;Wei, Wensheng
越来越多的证据表明，启动子和增强子可能与3D染色质结构有关，从而影响细胞功能。除了它们在形成典型染色质环中的作用外，启动子和增强剂在维持广泛的染色质组织方面还没有得到很好的研究。在这里，我们集中于预测与其他活性启动子/增强子(称为热点)形成许多3D接触的活性启动子/增强子，并通过CRISPR筛选确定了数十个对细胞生长和生存至关重要的基因座。我们发现，一个重要热点的缺失可能会导致广泛的染色质组织和远端基因表达的变化。我们发现，热点的重要性并不是因为它们与对细胞存活至关重要的单个基因相关联，而是因为它们与多个调节失调的非必需基因相关联，从而协同影响细胞的适合性。
Increasing evidence shows that promoters and enhancers could be related to 3D chromatin structure, thus affecting cellular functions. Except for their roles in forming canonical chromatin loops, promoters and enhancers have not been well studied regarding the maintenance of broad chromatin organization. Here, we focused on the active promoters/enhancers predicted to form many 3D contacts with other active promoters/enhancers (referred to as hotspots) and identified dozens of loci essential for cell growth and survival through CRISPR screening. We found that the deletion of an essential hotspot could lead to changes in broad chromatin organization and the expression of distal genes. We showed that the essentiality of hotspots does not result from their association with individual genes that are essential for cell viability but rather from their association with multiple dysregulated non-essential genes to synergistically impact cell fitness.
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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：
64.5
作者：
Long, Hannah K.;Prescott, Sara L.;Wysocka, Joanna
通讯作者：
Wysocka, Joanna
DOI：
10.1126/science.aah7111
发表时间：
2017-01-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Liu SJ;Horlbeck MA;Cho SW;Birk HS;Malatesta M;He D;Attenello FJ;Villalta JE;Cho MY;Chen Y;Mandegar MA;Olvera MP;Gilbert LA;Conklin BR;Chang HY;Weissman JS;Lim DA
通讯作者：
Lim DA
影响因子：
12.3
作者：
Akdemir KC;Chin L
通讯作者：
Chin L
影响因子：
2.4
作者：
Grabow, Carsten;Grosskinsky, Stefan;Timme, Marc
通讯作者：
Timme, Marc