Interplay of BAF and MLL4 promotes cell type-specific enhancer activation.
Interplay of BAF and MLL4 promotes cell type-specific enhancer activation.
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BAF和MLL4的相互作用促进细胞类型特异性增强子激活。
DOI：
10.1038/s41467-021-21893-y
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发表时间：
2021-03-12
影响因子：
16.6
通讯作者：
Ge K
中科院分区：
文献类型：
--
作者：
Park YK;Lee JE;Yan Z;McKernan K;O'Haren T;Wang W;Peng W;Ge K
细胞类型特异性增强子通过谱系决定转录因子（LDTF）和染色质调节因子的协调作用激活。SWI/SNF染色质重塑复合物BAF和组蛋白H3 K4甲基转移酶MLL 4（KMT 2D）都涉及增强子激活。然而，BAF和MLL 4在增强子激活中的相互作用仍不清楚。使用脂肪生成作为模型系统，我们确定BAF作为主要的SWI/SNF复合物，其与MLL 4和LDTF共定位于活性增强子上，并且是细胞分化所需的。相比之下，富含启动子的SWI/SNF复合物PBAF不适于脂肪形成。通过消耗细胞中的BAF亚基SMARCA 4（BRG 1）和SMARCB 1（SNF 5）以及MLL 4，我们表明BAF和MLL 4在脂肪形成之前和期间相互调节活性增强子的结合。通过关注成脂先锋转录因子C/EBPβ激活增强子而不诱导细胞分化，我们为BAF和MLL 4在激活细胞类型特异性增强子方面的相互依赖关系提供了直接证据。总之，这些发现揭示了BAF和MLL 4在促进细胞类型特异性增强子的LDTF依赖性活化方面的正反馈。SWI/SNF复合物BAF和组蛋白H3 K4甲基转移酶MLL 4（KMT 2D）在增强子激活中起关键作用，然而它们之间的相互作用仍不清楚。在这里，作者表明，BAF和MLL 4是相互依赖的，在脂肪形成过程中，通过谱系决定转录因子促进增强子激活。
Cell type-specific enhancers are activated by coordinated actions of lineage-determining transcription factors (LDTFs) and chromatin regulators. The SWI/SNF chromatin remodeling complex BAF and the histone H3K4 methyltransferase MLL4 (KMT2D) are both implicated in enhancer activation. However, the interplay between BAF and MLL4 in enhancer activation remains unclear. Using adipogenesis as a model system, we identify BAF as the major SWI/SNF complex that colocalizes with MLL4 and LDTFs on active enhancers and is required for cell differentiation. In contrast, the promoter enriched SWI/SNF complex PBAF is dispensable for adipogenesis. By depleting BAF subunits SMARCA4 (BRG1) and SMARCB1 (SNF5) as well as MLL4 in cells, we show that BAF and MLL4 reciprocally regulate each other’s binding on active enhancers before and during adipogenesis. By focusing on enhancer activation by the adipogenic pioneer transcription factor C/EBPβ without inducing cell differentiation, we provide direct evidence for an interdependent relationship between BAF and MLL4 in activating cell type-specific enhancers. Together, these findings reveal a positive feedback between BAF and MLL4 in promoting LDTF-dependent activation of cell type-specific enhancers. The SWI/SNF complex BAF and the histone H3K4 methyltransferase MLL4 (KMT2D) play critical roles in enhancer activation, however the interplay between them has remained unclear. Here the authors show that BAF and MLL4 are interdependent in promoting enhancer activation by lineage-determining transcription factors during adipogenesis.
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影响因子：
12.3
作者：
Bao X;Rubin AJ;Qu K;Zhang J;Giresi PG;Chang HY;Khavari PA
通讯作者：
Khavari PA
影响因子：
30.8
作者：
He, Housheng Hansen;Meyer, Clifford A.;Shin, Hyunjin;Bailey, Shannon T.;Wei, Gang;Wang, Qianben;Zhang, Yong;Xu, Kexin;Ni, Min;Lupien, Mathieu;Mieczkowski, Piotr;Lieb, Jason D.;Zhao, Keji;Brown, Myles;Liu, X. Shirley
通讯作者：
Liu, X. Shirley
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：
10.1038/nrm3949
发表时间：
2015-03
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Heinz S;Romanoski CE;Benner C;Glass CK
通讯作者：
Glass CK
影响因子：
16.6
作者：
Gatchalian J;Malik S;Ho J;Lee DS;Kelso TWR;Shokhirev MN;Dixon JR;Hargreaves DC
通讯作者：
Hargreaves DC