BAF60A mediates interactions between the microphthalmia-associated transcription factor and the BRG1-containing SWI/SNF complex during melanocyte differentiation

J Cell Physiol. 2019 Jul;234(7):11780-11791. doi: 10.1002/jcp.27840. Epub 2018 Dec 4.


SWI/SNF chromatin remodeling enzymes are multisubunit complexes that contain one of two catalytic subunits, BRG1 or BRM and 9-11 additional subunits called BRG1 or BRM-associated factors (BAFs). BRG1 interacts with the microphthalmia-associated transcription factor (MITF) and is required for melanocyte development in vitro and in vivo. The subunits of SWI/SNF that mediate interactions between BRG1 and MITF have not been elucidated. Three mutually exclusive isoforms of a 60-kDa subunit (BAF60A, B, or C) often facilitate interactions with transcription factors during lineage specification. We tested the hypothesis that a BAF60 subunit promotes interactions between MITF and the BRG1-containing SWI/SNF complex. We found that MITF can physically interact with BAF60A, BAF60B, and BAF60C. The interaction between MITF and BAF60A required the basic helix-loop-helix domain of MITF. Recombinant BAF60A pulled down recombinant MITF, suggesting that the interaction can occur in the absence of other SWI/SNF subunits and other transcriptional regulators of the melanocyte lineage. Depletion of BAF60A in differentiating melanoblasts inhibited melanin synthesis and expression of MITF target genes. MITF promoted BAF60A recruitment to melanocyte-specific promoters, and BAF60A was required to promote BRG1 recruitment and chromatin remodeling. Thus, BAF60A promotes interactions between MITF and the SWI/SNF complex and is required for melanocyte differentiation.

Keywords: BAF60A; chromatin remodeling; melanocyte differentiation; microphthalmia-associated transcription factor (MITF).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Differentiation* / genetics
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA Helicases / metabolism*
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Melanins / biosynthesis
  • Melanocytes / cytology*
  • Melanocytes / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Mice
  • Microphthalmia-Associated Transcription Factor / chemistry
  • Microphthalmia-Associated Transcription Factor / metabolism*
  • Models, Biological
  • Nuclear Proteins / metabolism*
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Protein Subunits / metabolism
  • Transcription Factors / metabolism*


  • Chromosomal Proteins, Non-Histone
  • Melanins
  • Membrane Glycoproteins
  • Microphthalmia-Associated Transcription Factor
  • Nuclear Proteins
  • Protein Subunits
  • SMARCD1 protein, human
  • SWI-SNF-B chromatin-remodeling complex
  • Smarcd1 protein, mouse
  • Transcription Factors
  • Oxidoreductases
  • TYRP1 protein, human
  • SMARCA4 protein, human
  • DNA Helicases