瑞士/瑞士法郎
增强子
染色质
SMARCA4型
转录因子
染色质重塑
表观遗传学
染色质结构重塑复合物
相互作用体
生物
遗传学
计算生物学
细胞生物学
基因
作者
Bennett Wolf,Yanding Zhao,Andrew McCray,William H. Hawk,Luke T Deary,Nicholas W Sugiarto,Ian S LaCroix,Scott A. Gerber,Chao Cheng,Xiaofeng Wang
标识
DOI:10.1038/s41594-022-00880-x
摘要
The mechanism controlling the dynamic targeting of SWI/SNF has long been postulated to be coordinated by transcription factors (TFs), yet demonstrating a specific TF influence has proven difficult. Here we take a multi-omics approach to interrogate transient SWI/SNF interactors, chromatin targeting and the resulting three-dimensional epigenetic landscape. We utilize the labeling technique TurboID to map the SWI/SNF interactome and identify the activator protein-1 (AP-1) family members as critical interacting partners for SWI/SNF complexes. CUT&RUN profiling demonstrates SWI/SNF targeting enrichment at AP-1 bound loci, as well as SWI/SNF–AP-1 cooperation in chromatin targeting. HiChIP reveals AP-1–SWI/SNF-dependent restructuring of the three-dimensional promoter–enhancer architecture and generation of enhancer hubs. Through interrogation of the SWI/SNF–AP-1 interaction, we demonstrate an SWI/SNF dependency on AP-1-mediated chromatin localization. We propose that pioneer factors, such as AP-1, bind and target SWI/SNF to inactive chromatin, where it restructures the genomic landscape into an active state through epigenetic rewiring spanning multiple dimensions. The mechanism controlling SWI/SNF chromatin remodeler targeting is incompletely understood. This study demonstrates that AP-1 transcription factors guide SWI/SNF to genomic regions, resulting in 3D genomic architecture alterations.
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