Language

English

Publication Date

1-1-2023

Journal

Nature Structural & Molecular Biology

DOI

10.1038/s41594-022-00880-x

PMID

36522426

PMCID

PMC10513740

PubMedCentral® Posted Date

9-21-2023

PubMedCentral® Full Text Version

Author MSS

Abstract

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.

Keywords

Transcription Factor AP-1, Chromatin, Chromatin Assembly and Disassembly, Nuclear Proteins, Promoter Regions, Genetic

Published Open-Access

yes

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