A conserved BAH module within mammalian BAHD1 connects H3K27me3 to Polycomb gene silencing.
A conserved BAH module within mammalian BAHD1 connects H3K27me3 to Polycomb gene silencing.
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DOI：
10.1093/nar/gkab210
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发表时间：
2021-05-07
影响因子：
14.9
通讯作者：
Wang GG
中科院分区：
文献类型：
--
作者：
Fan H;Guo Y;Tsai YH;Storey AJ;Kim A;Gong W;Edmondson RD;Mackintosh SG;Li H;Byrum SD;Tackett AJ;Cai L;Wang GG
组蛋白H3赖氨酸27（H3 K27 me 3）的三甲基化对于基因沉默和印记、（表观）基因组组织和生物体发育是重要的。在一个流行的模型中，哺乳动物细胞中H3 K27 me 3的功能读出是通过H3 K27 me 3识别chromodomain实现的，该chromodomain位于典型的Polycomb抑制复合物1（cPRC 1）的chromobox（CBX）组分内，其诱导染色质压缩和基因抑制。在这里，我们报告说，结合H3 K27 me 3的溴邻近同源（BAH）域内含有BAH域的蛋白1（BAHD 1）所需的整体BAHD 1靶向染色质和哺乳动物细胞中的H3 K27 me 3划界基因的最佳抑制。通过点突变破坏BAHD 1BAH和H3 K27 me 3之间的直接相互作用导致染色质重塑，特别是在其Polycomb基因靶标处增加组蛋白乙酰化。携带H3 K27 me 3相互作用缺陷突变的Bahd 1BAH小鼠会导致明显的胚胎致死性，表明正常发育需要这种途径。总之，这项工作证明了一个H3 K27 me 3启动的信号级联，通过一个保守的BAH '阅读器'模块BAHD 1在哺乳动物。哺乳动物H3 K27 me 3-转导途径通过BAHD 1的H3 K27 me 3-特异性“阅读器”模块（BAH）操作，BAH与辅阻遏物（HDAC等）组装复合物，用于抑制组蛋白乙酰化和抑制Polycomb靶基因的表达。
Trimethylation of histone H3 lysine 27 (H3K27me3) is important for gene silencing and imprinting, (epi)genome organization and organismal development. In a prevalent model, the functional readout of H3K27me3 in mammalian cells is achieved through the H3K27me3-recognizing chromodomain harbored within the chromobox (CBX) component of canonical Polycomb repressive complex 1 (cPRC1), which induces chromatin compaction and gene repression. Here, we report that binding of H3K27me3 by a Bromo Adjacent Homology (BAH) domain harbored within BAH domain-containing protein 1 (BAHD1) is required for overall BAHD1 targeting to chromatin and for optimal repression of the H3K27me3-demarcated genes in mammalian cells. Disruption of direct interaction between BAHD1BAH and H3K27me3 by point mutagenesis leads to chromatin remodeling, notably, increased histone acetylation, at its Polycomb gene targets. Mice carrying an H3K27me3-interaction-defective mutation of Bahd1BAH causes marked embryonic lethality, showing a requirement of this pathway for normal development. Altogether, this work demonstrates an H3K27me3-initiated signaling cascade that operates through a conserved BAH ‘reader’ module within BAHD1 in mammals. A mammalian H3K27me3-transduction pathway operates through an H3K27me3-specific ‘reader’ module (BAH) of BAHD1, which assembles a complex with corepressors (HDACs and others) for suppressing histone acetylation and repressing expression at Polycomb target genes.
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影响因子：
10.5
作者：
Min, JR;Zhang, Y;Xu, RM
通讯作者：
Xu, RM
影响因子：
3.7
作者：
Libertin, Emanuele;Lebreton, Alice;Bierne, Helene
通讯作者：
Bierne, Helene
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
30.8
作者：
Li, Zicong;Fu, Xing;He, Yuehui
通讯作者：
He, Yuehui
DOI：
10.1038/nrm4067
发表时间：
2015-11
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Blackledge NP;Rose NR;Klose RJ
通讯作者：
Klose RJ