
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.23.609212
preprint
1
Article
The SWI/SNF PBAF complex facilitates REST occupancy at repressive chromatin
Grossi Elena http://orcid.org/0000-0003-3938-5000

Nguyen Christie B.
Carcamo Saul
Moran Shannon
Callaú Valentina Kirigin
Filipescu Dan
Hasson Dan
Bernstein Emily
23 8 2024
2024.08.23.609212https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.23.609212
nihpp-2024.08.23.609212.pdf
Summary

Multimeric SWI/SNF chromatin remodelers assemble into discrete conformations with unique complex functionalities difficult to dissect. Distinct cancers harbor mutations in specific subunits, altering the chromatin landscape, such as the PBAF-specific component ARID2 in melanoma. Here, we performed comprehensive epigenomic profiling of SWI/SNF complexes and their associated chromatin states in melanoma and melanocytes and uncovered a subset of PBAF-exclusive regions that coexist with PRC2 and repressive chromatin. Time-resolved approaches revealed that PBAF regions are generally less sensitive to ATPase-mediated remodeling than BAF sites. Moreover, PBAF/PRC2-bound loci are enriched for REST, a transcription factor that represses neuronal genes. In turn, absence of ARID2 and consequent PBAF complex disruption hinders the ability of REST to bind and inactivate its targets, leading to upregulation of synaptic transcripts. Remarkably, this gene signature is conserved in melanoma patients with ARID2 mutations. In sum, we demonstrate a unique role for PBAF in generating accessibility for a silencing transcription factor at repressed chromatin, with important implications for disease.
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