Transcriptional regulation and chromatin architecture maintenance are decoupled functions at the Sox2 locus.
Transcriptional regulation and chromatin architecture maintenance are decoupled functions at the Sox2 locus.
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DOI：
10.1101/gad.349489.122
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发表时间：
2022-06-01
影响因子：
10.5
通讯作者：
Sexton, Tom
中科院分区：
文献类型：
--
作者：
Taylor, Tiegh;Sikorska, Natalia;Shchuka, Virlana M.;Chahar, Sanjay;Ji, Chenfan;Macpherson, Neil N.;Moorthy, Sakthi D.;de Kort, Marit A. C.;Mullany, Shanelle;Khader, Nawrah;Gillespie, Zoe E.;Langroudi, Lida;Tobias, Ian C.;Lenstra, Tineke L.;Mitchell, Jennifer A.;Sexton, Tom
在这里，Taylor等人研究了远端调控元件如何控制发育过程中谱系特化中的基因转录和染色质拓扑结构。通过对小鼠胚胎干细胞中Sox 2基因座的等位基因特异性基因组编辑和染色质相互作用分析，他们发现转录控制和染色质结构之间存在惊人的脱节，并将几乎所有Sox 2转录激活追溯到少数关键转录因子结合位点，这些位点的缺失对启动子-增强子相互作用频率或拓扑结构域组织没有影响。远端调控元件如何控制基因转录和染色质拓扑结构尚不清楚，但这些过程在发育过程中的谱系特化中密切相关。通过对小鼠胚胎干细胞中Sox 2基因座的等位基因特异性基因组编辑和染色质相互作用分析，我们发现转录控制和染色质结构之间存在显著的脱节。我们追踪几乎所有的Sox 2转录激活到少数关键转录因子结合位点，其缺失对启动子-增强子相互作用频率或拓扑结构域组织没有影响。局部染色质结构的维持，包括在Sox 2增强子下游的拓扑相关结构域（topologically associated domain，简称CTCF）边界，广泛分布于多个转录因子结合区域，并以CTCF独立的方式维持。此外，异位染色质环形成的启动子-增强子相互作用的部分中断对Sox 2转录没有影响。这些发现表明，许多转录因子参与调节染色质结构独立CTCF。
Here, Taylor et al. investigated how distal regulatory elements control gene transcription and chromatin topology in lineage specification during development. Through allele-specific genome editing and chromatin interaction analyses of the Sox2 locus in mouse embryonic stem cells, they found a striking disconnection between transcriptional control and chromatin architecture, and traced nearly all Sox2 transcriptional activation to a small number of key transcription factor binding sites, whose deletions have no effect on promoter–enhancer interaction frequencies or topological domain organization. How distal regulatory elements control gene transcription and chromatin topology is not clearly defined, yet these processes are closely linked in lineage specification during development. Through allele-specific genome editing and chromatin interaction analyses of the Sox2 locus in mouse embryonic stem cells, we found a striking disconnection between transcriptional control and chromatin architecture. We traced nearly all Sox2 transcriptional activation to a small number of key transcription factor binding sites, whose deletions have no effect on promoter–enhancer interaction frequencies or topological domain organization. Local chromatin architecture maintenance, including at the topologically associating domain (TAD) boundary downstream from the Sox2 enhancer, is widely distributed over multiple transcription factor-bound regions and maintained in a CTCF-independent manner. Furthermore, partial disruption of promoter–enhancer interactions by ectopic chromatin loop formation has no effect on Sox2 transcription. These findings indicate that many transcription factors are involved in modulating chromatin architecture independently of CTCF.
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影响因子：
46.9
作者：
Doench JG;Fusi N;Sullender M;Hegde M;Vaimberg EW;Donovan KF;Smith I;Tothova Z;Wilen C;Orchard R;Virgin HW;Listgarten J;Root DE
通讯作者：
Root DE
影响因子：
16.6
作者：
Crump NT;Ballabio E;Godfrey L;Thorne R;Repapi E;Kerry J;Tapia M;Hua P;Lagerholm C;Filippakopoulos P;Davies JOJ;Milne TA
通讯作者：
Milne TA
影响因子：
64.5
作者：
Dowen JM;Fan ZP;Hnisz D;Ren G;Abraham BJ;Zhang LN;Weintraub AS;Schujiers J;Lee TI;Zhao K;Young RA
通讯作者：
Young RA
影响因子：
30.8
作者：
Allahyar, Amin;Vermeulen, Carlo;de Laat, Wouter
通讯作者：
de Laat, Wouter
影响因子：
64.5
作者：
Deng W;Lee J;Wang H;Miller J;Reik A;Gregory PD;Dean A;Blobel GA
通讯作者：
Blobel GA