BACH1 recruits NANOG and histone H3 lysine 4 methyltransferase MLL/SET1 complexes to regulate enhancer-promoter activity and maintains pluripotency.
BACH1 recruits NANOG and histone H3 lysine 4 methyltransferase MLL/SET1 complexes to regulate enhancer-promoter activity and maintains pluripotency.
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BACH1 招募 NANOG 和组蛋白 H3 赖氨酸 4 甲基转移酶 MLL/SET1 复合物来调节增强子-启动子活性并维持多能性
DOI：
10.1093/nar/gkab034
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发表时间：
2021-02-26
影响因子：
14.9
通讯作者：
Meng D
中科院分区：
文献类型：
--
作者：
Niu C;Wang S;Guo J;Wei X;Jia M;Chen Z;Gong W;Qin Y;Wang X;Zhi X;Lu M;Chen S;Gu M;Zhang J;Han JJ;Lan F;Meng D
干细胞身份的维持需要增强子活性的适当调节。转录因子OCT 4/SOX 2/NANOG和组蛋白甲基转移酶复合物MLL/SET 1都被证明可以调节增强子活性，但它们在胚胎干细胞（ESC）中的调节方式仍有待进一步研究。在这里，我们报告了一个转录因子BACH 1，它直接与OCT 4/SOX 2/NANOG（OSN）和MLL/SET 1甲基转移酶复合物相互作用，并保持小鼠胚胎干细胞（mESC）的多能性。BTB结构域和BACH 1的bZIP结构域是这些相互作用和多能性维持所必需的。BACH 1的缺失降低了NANOG和MLL 1/SET 1复合物之间的相互作用，并降低了它们在染色质上的占据率，进一步降低了基因启动子和（超级）增强子上的H3赖氨酸4三甲基化（H3 K4 me 3）水平，导致增强子活性和转录活性降低，尤其是在茎相关基因上。此外，BACH 1通过染色质成环和调节远程NANOG结合，微调增强子-启动子活性和基因表达来招募NANOG。总的来说，这些观察结果表明，BACH 1通过将NANOG和MLL/SET 1复合物募集到染色质并维持H3 K4的三甲基化状态和增强子-启动子活性，特别是在干细胞相关基因上，来维持ESC中的多能性。
Maintenance of stem-cell identity requires proper regulation of enhancer activity. Both transcription factors OCT4/SOX2/NANOG and histone methyltransferase complexes MLL/SET1 were shown to regulate enhancer activity, but how they are regulated in embryonic stem cells (ESCs) remains further studies. Here, we report a transcription factor BACH1, which directly interacts with OCT4/SOX2/NANOG (OSN) and MLL/SET1 methyltransferase complexes and maintains pluripotency in mouse ESCs (mESCs). BTB domain and bZIP domain of BACH1 are required for these interactions and pluripotency maintenance. Loss of BACH1 reduced the interaction between NANOG and MLL1/SET1 complexes, and decreased their occupancy on chromatin, and further decreased H3 lysine 4 trimethylation (H3K4me3) level on gene promoters and (super-) enhancers, leading to decreased enhancer activity and transcription activity, especially on stemness-related genes. Moreover, BACH1 recruited NANOG through chromatin looping and regulated remote NANOG binding, fine-tuning enhancer–promoter activity and gene expression. Collectively, these observations suggest that BACH1 maintains pluripotency in ESCs by recruiting NANOG and MLL/SET1 complexes to chromatin and maintaining the trimethylated state of H3K4 and enhancer–promoter activity, especially on stemness-related genes.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
48
作者：
Langmead, Ben;Salzberg, Steven L.
通讯作者：
Salzberg, Steven L.
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
64.5
作者：
Gifford CA;Ziller MJ;Gu H;Trapnell C;Donaghey J;Tsankov A;Shalek AK;Kelley DR;Shishkin AA;Issner R;Zhang X;Coyne M;Fostel JL;Holmes L;Meldrim J;Guttman M;Epstein C;Park H;Kohlbacher O;Rinn J;Gnirke A;Lander ES;Bernstein BE;Meissner A
通讯作者：
Meissner A
影响因子：
64.8
作者：
Lee, Jiyoung;Yesilkanal, Ali E.;Rosner, Marsha Rich
通讯作者：
Rosner, Marsha Rich