1. Altered BAF occupancy and transcription factor dynamics in PBAF-deficient melanoma.
- Author
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Carcamo S, Nguyen CB, Grossi E, Filipescu D, Alpsoy A, Dhiman A, Sun D, Narang S, Imig J, Martin TC, Parsons R, Aifantis I, Tsirigos A, Aguirre-Ghiso JA, Dykhuizen EC, Hasson D, and Bernstein E
- Subjects
- Animals, Chromatin, Chromatin Assembly and Disassembly, Gene Expression Regulation, Humans, Chromosomal Proteins, Non-Histone, Melanoma genetics, Transcription Factors genetics, Transcription Factors metabolism
- Abstract
ARID2 is the most recurrently mutated SWI/SNF complex member in melanoma; however, its tumor-suppressive mechanisms in the context of the chromatin landscape remain to be elucidated. Here, we model ARID2 deficiency in melanoma cells, which results in defective PBAF complex assembly with a concomitant genomic redistribution of the BAF complex. Upon ARID2 depletion, a subset of PBAF and shared BAF-PBAF-occupied regions displays diminished chromatin accessibility and associated gene expression, while BAF-occupied enhancers gain chromatin accessibility and expression of genes linked to the process of invasion. As a function of altered accessibility, the genomic occupancy of melanoma-relevant transcription factors is affected and significantly correlates with the observed transcriptional changes. We further demonstrate that ARID2-deficient cells acquire the ability to colonize distal organs in multiple animal models. Taken together, our results reveal a role for ARID2 in mediating BAF and PBAF subcomplex chromatin dynamics with consequences for melanoma metastasis., Competing Interests: Declaration of interests J.A.A.-G. is a scientific co-founder, scientific advisory board member, and equity owner of HiberCell and receives financial compensation as a consultant., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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