SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters.
SMARCB1 is required for widespread BAF complex-mediated activation of enhancers and bivalent promoters.
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DOI：
10.1038/ng.3958
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发表时间：
2017-11
期刊：
影响因子：
30.8
通讯作者：
Kadoch C
中科院分区：
文献类型：
--
作者：
Nakayama RT;Pulice JL;Valencia AM;McBride MJ;McKenzie ZM;Gillespie MA;Ku WL;Teng M;Cui K;Williams RT;Cassel SH;Qing H;Widmer CJ;Demetri GD;Irizarry RA;Zhao K;Ranish JA;Kadoch C
Perturbations to mammalian SWI/SNF (BAF) complexes contribute to over 20% of human cancers, with driving roles first identified in malignant rhabdoid tumor (MRT), an aggressive pediatric cancer characterized by biallelic inactivation of the core BAF complex subunit SMARCB1 (BAF47). However, the mechanism by which this alteration contributes to tumorigenesis remains poorly understood. We find that BAF47 loss destabilizes BAF complexes on chromatin, absent significant changes in intra-complex integrity. Rescue of BAF47 in BAF47-deficient sarcoma cell lines results in increased genome-wide BAF complex occupancy, facilitating widespread enhancer activation and opposition of polycomb-mediated repression at bivalent promoters. We demonstrate differential regulation by BAF and PBAF complexes at enhancers and promoters, respectively, suggesting distinct functions of each complex which are perturbed upon BAF47 loss. Our results demonstrate collaborative mechanisms of mSWI/SNF-mediated gene activation, identifying functions that are coopted or abated to drive human cancers and developmental disorders.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
哺乳动物SWI/SNF复合物的蛋白质组学和生物信息学分析确定了在人类恶性肿瘤中的广泛作用。
影响因子：
30.8
作者：
Kadoch, Cigall;Hargreaves, Diana C.;Hodges, Courtney;Elias, Laura;Ho, Lena;Ranish, Jeff;Crabtree, Gerald R.
通讯作者：
Crabtree, Gerald R.
DOI：
10.1186/1748-7188-9-14
发表时间：
2014
期刊：
Algorithms for molecular biology : AMB
影响因子：
--
作者：
Filippova D;Patro R;Duggal G;Kingsford C
通讯作者：
Kingsford C
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：
8
作者：
Doan, DN;Veal, TM;Imbalzano, AN
通讯作者：
Imbalzano, AN