ARID1A-dependent maintenance of H3.3 is required for repressive CHD4-ZMYND8 chromatin interactions at super-enhancers.
ARID1A-dependent maintenance of H3.3 is required for repressive CHD4-ZMYND8 chromatin interactions at super-enhancers.
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H3.3的ARID 1A依赖性维持是在超级增强子处抑制性CHD 4-ZMYND 8染色质相互作用所必需的。
DOI：
10.1186/s12915-022-01407-y
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发表时间：
2022-09-25
期刊：
影响因子：
5.4
通讯作者：
Chandler, Ronald L.
中科院分区：
文献类型：
--
作者：
Reske, Jake J.;Wilson, Mike R.;Armistead, Brooke;Harkins, Shannon;Perez, Cristina;Hrit, Joel;Adams, Marie;Rothbart, Scott B.;Missmer, Stacey A.;Fazleabas, Asgerally T.;Chandler, Ronald L.
SWI/SNF(BAF)染色质重塑复合体通过促进多种DNA结合因子和染色质调节因子的可及性来调节谱系特异性增强子的活性。此外，已知它们通过调节组蛋白翻译后修饰和核小体组成来调节表观基因组的功能，尽管SWI/SNF复合体管理表观基因组的方式仍然知之甚少。在这里，我们研究了ARID1A的功能，它是某些哺乳动物SWI/SNF染色质重塑复合体的一个亚单位，与起源于子宫内膜的恶性肿瘤和良性疾病有关。通过对人子宫内膜异位上皮细胞的全基因组分析，我们发现超过一半的ARID1A结合位点由变异组蛋白H3.3标记，其中包括诸如超级增强子等活性调控元件。ARID1A基因敲除导致H3.3在ARID1A结合的活性调控元件上的典型H3.1/3.2的耗尽和获得，并伴随着H3.3向基因元件的重新分布。ARID1A与抑制性染色质重构体CHD4(NuRD)的相互作用与H3.3有关，而ARID1A是CHD4募集到H3.3所必需的。ZMYND8与CHD4相互作用，抑制ARID1A、CHD4和ZMYND8共同结合的H3.3+H4K16ac+超级增强子的子集，这些超增强子靠近调控细胞外基质、运动性、粘附性和上皮向间充质转化的基因。此外，在人类子宫内膜瘤中也观察到了这些基因表达的变化。这些研究表明，含有ARID1A的BAF复合体是维持组蛋白变异体H3.3在活性调控元件(如超级增强子)处所必需的，而这一功能是替代染色质重构体的生理相关活动所必需的。网上版载有补充材料，可在10.1186/s12915-022-01407-y查阅。
SWI/SNF (BAF) chromatin remodeling complexes regulate lineage-specific enhancer activity by promoting accessibility for diverse DNA-binding factors and chromatin regulators. Additionally, they are known to modulate the function of the epigenome through regulation of histone post-translational modifications and nucleosome composition, although the way SWI/SNF complexes govern the epigenome remains poorly understood. Here, we investigate the function of ARID1A, a subunit of certain mammalian SWI/SNF chromatin remodeling complexes associated with malignancies and benign diseases originating from the uterine endometrium. Through genome-wide analysis of human endometriotic epithelial cells, we show that more than half of ARID1A binding sites are marked by the variant histone H3.3, including active regulatory elements such as super-enhancers. ARID1A knockdown leads to H3.3 depletion and gain of canonical H3.1/3.2 at ARID1A-bound active regulatory elements, and a concomitant redistribution of H3.3 toward genic elements. ARID1A interactions with the repressive chromatin remodeler CHD4 (NuRD) are associated with H3.3, and ARID1A is required for CHD4 recruitment to H3.3. ZMYND8 interacts with CHD4 to suppress a subset of ARID1A, CHD4, and ZMYND8 co-bound, H3.3+ H4K16ac+ super-enhancers near genes governing extracellular matrix, motility, adhesion, and epithelial-to-mesenchymal transition. Moreover, these gene expression alterations are observed in human endometriomas. These studies demonstrate that ARID1A-containing BAF complexes are required for maintenance of the histone variant H3.3 at active regulatory elements, such as super-enhancers, and this function is required for the physiologically relevant activities of alternative chromatin remodelers. The online version contains supplementary material available at 10.1186/s12915-022-01407-y.
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影响因子：
4.8
作者：
Adhikary, Santanu;Sanyal, Sulagna;Das, Chandrima
通讯作者：
Das, Chandrima
影响因子：
50.3
作者：
Berger AC;Korkut A;Kanchi RS;Hegde AM;Lenoir W;Liu W;Liu Y;Fan H;Shen H;Ravikumar V;Rao A;Schultz A;Li X;Sumazin P;Williams C;Mestdagh P;Gunaratne PH;Yau C;Bowlby R;Robertson AG;Tiezzi DG;Wang C;Cherniack AD;Godwin AK;Kuderer NM;Rader JS;Zuna RE;Sood AK;Lazar AJ;Ojesina AI;Adebamowo C;Adebamowo SN;Baggerly KA;Chen TW;Chiu HS;Lefever S;Liu L;MacKenzie K;Orsulic S;Roszik J;Shelley CS;Song Q;Vellano CP;Wentzensen N;Cancer Genome Atlas Research Network;Weinstein JN;Mills GB;Levine DA;Akbani R
通讯作者：
Akbani R
DOI：
10.1056/nejmoa1614814
发表时间：
2017-05-11
期刊：
The New England journal of medicine
影响因子：
--
作者：
Anglesio MS;Papadopoulos N;Ayhan A;Nazeran TM;Noë M;Horlings HM;Lum A;Jones S;Senz J;Seckin T;Ho J;Wu RC;Lac V;Ogawa H;Tessier-Cloutier B;Alhassan R;Wang A;Wang Y;Cohen JD;Wong F;Hasanovic A;Orr N;Zhang M;Popoli M;McMahon W;Wood LD;Mattox A;Allaire C;Segars J;Williams C;Tomasetti C;Boyd N;Kinzler KW;Gilks CB;Diaz L;Wang TL;Vogelstein B;Yong PJ;Huntsman DG;Shih IM
通讯作者：
Shih IM
影响因子：
16
作者：
Dechassa ML;Sabri A;Pondugula S;Kassabov SR;Chatterjee N;Kladde MP;Bartholomew B
通讯作者：
Bartholomew B
影响因子：
14.9
作者：
Cheneby, Jeanne;Menetrier, Zacharie;Ballester, Benoit
通讯作者：
Ballester, Benoit