Altered BAF occupancy and transcription factor dynamics in PBAF-deficient melanoma.

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. Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Saul Carcamo, Christie B Nguyen, Elena Grossi, Dan Filipescu, Aktan Alpsoy, Alisha Dhiman, Dan Sun, Sonali Narang, Jochen Imig, Tiphaine C Martin, Ramon Parsons, Iannis Aifantis, Aristotelis Tsirigos, Julio A Aguirre-Ghiso, Emily C Dykhuizen, Dan Hasson, Emily Bernstein. Altered BAF occupancy and transcription factor dynamics in PBAF-deficient melanoma. Cell reports. 2022 Apr 05;39(1):110637

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PMID: 35385731

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