The PBAF chromatin remodeling complex contributes to metal homeostasis through MTF1 regulation.

Abstract

Chromatin remodeling by SWI/SNF complexes is essential for transcriptional regulation, yet how distinct SWI/SNF subcomplexes contribute to cellular stress responses remains incompletely understood. Here, we identify a specific role for the PBAF subunit Baf180 in regulating metal-responsive transcription and adaptation to metal stress in proliferating myoblasts. While knockdown (KD) of the BAF-specific subunit Baf250a or the ncBAF-specific subunit Brd9 significantly impairs myoblast proliferation, KD of the PBAF-specific subunit Baf180 has no effect under basal conditions. Notably, supplementation with copper (Cu) or zinc (Zn) restores proliferative capacity in Baf250a- and Brd9-deficient myoblasts. In contrast, Baf180-depleted myoblasts exhibit impaired proliferation upon metal exposure, accompanied by selective dysregulation of genes involved in Cu and Zn homeostasis. Transcriptomic and chromatin profiling further reveal that loss of Baf180 alters the activity of metal-regulatory transcription factor 1 (MTF1), including reduced chromatin occupancy at metal-responsive loci. Together, these findings support a model in which PBAF promotes metal-responsive gene regulation to maintain metal homeostasis and sustain myoblast proliferation, uncovering a previously unrecognized link between nucleosome remodeling and metal homeostasis during muscle cell proliferation.