%0 Journal Article
%T A disordered region controls cBAF activity via condensation and partner recruitment.
%A Patil A
%A Strom AR
%A Paulo JA
%A Collings CK
%A Ruff KM
%A Shinn MK
%A Sankar A
%A Cervantes KS
%A Wauer T
%A St Laurent JD
%A Xu G
%A Becker LA
%A Gygi SP
%A Pappu RV
%A Brangwynne CP
%A Kadoch C
%J Cell
%V 186
%N 22
%D 2023 10 26
%M 37788668
%F 66.85
%R 10.1016/j.cell.2023.08.032
%X 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.