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

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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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.

Original languageEnglish (US)
Article number110637
JournalCell Reports
Volume39
Issue number1
DOIs
StatePublished - Apr 5 2022
Externally publishedYes

Keywords

  • ARID2
  • BAF
  • chromatin
  • CP: Cancer
  • invasion
  • melanoma
  • PBAF
  • SWI/SNF
  • transcription factors

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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