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

Cell Rep. 2022 Apr 5;39(1):110637. doi: 10.1016/j.celrep.2022.110637.


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.

Keywords: ARID2; BAF; CP: Cancer; PBAF; SWI/SNF; chromatin; invasion; melanoma; transcription factors.

MeSH terms

  • Animals
  • Chromatin
  • Chromatin Assembly and Disassembly
  • Chromosomal Proteins, Non-Histone*
  • Gene Expression Regulation
  • Humans
  • Melanoma* / genetics
  • Transcription Factors* / genetics
  • Transcription Factors* / metabolism


  • ARID2 protein, human
  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • SWI-SNF-B chromatin-remodeling complex
  • Transcription Factors