A disordered region controls cBAF activity via condensation and partner recruitment

Ajinkya Patil, Amy R. Strom, Joao A. Paulo, Clayton K. Collings, Kiersten M. Ruff, Min Kyung Shinn, Akshay Sankar, Kasey S. Cervantes, Tobias Wauer, Jessica D. St. Laurent, Grace Xu, Lindsay A. Becker, Steven P. Gygi, Rohit V. Pappu, Clifford P. Brangwynne, Cigall Kadoch

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Intrinsically disordered regions (IDRs) represent a large percentage of overall nuclear protein content. The prevailing dogma is that IDRs engage in non-specific interactions because they are poorly constrained by evolutionary selection. Here, we demonstrate that condensate formation and heterotypic interactions are distinct and separable features of an IDR within the ARID1A/B subunits of the mSWI/SNF chromatin remodeler, cBAF, and establish distinct “sequence grammars” underlying each contribution. Condensation is driven by uniformly distributed tyrosine residues, and partner interactions are mediated by non-random blocks rich in alanine, glycine, and glutamine residues. These features concentrate a specific cBAF protein-protein interaction network and are essential for chromatin localization and activity. Importantly, human disease-associated perturbations in ARID1B IDR sequence grammars disrupt cBAF function in cells. Together, these data identify IDR contributions to chromatin remodeling and explain how phase separation provides a mechanism through which both genomic localization and functional partner recruitment are achieved.

Original languageEnglish (US)
Pages (from-to)4936-4955.e26
JournalCell
Volume186
Issue number22
DOIs
StatePublished - Oct 26 2023

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology

Keywords

  • ARID1A
  • ARID1B
  • ATP-dependent chromatin remodeling
  • IDRs
  • cBAF complexes
  • condensates
  • intrinsically disordered regions
  • mammalian SWI/SNF complexes
  • phase separation
  • transcription factors

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