Nucleolar Condensation Orchestrates rRNA-dependent Mobility and Spatiotemporally Enriches rDNA-binding of Human Chromatin Remodeler BRG1

Abstract

As key regulators of genome access via nucleosome translocation/ejection, SWI/SNF chromatin remodeling complexes share a core ATPase/translocase subunit, BRG1, central to their activity. Despite recent discovery of spatially clustered intranuclear "hotspots" where various SWI/SNF remodelers preferentially bind, the mechanistic driving force underlying such heterogeneous organization remains unclear. Herein, we show that human BRG1 undergoes condensation in vitro and in live cell nucleus, mediated by its IDR-rich C-terminus (BRG1C). Intranuclear condensates of BRG1C form across a wide range of (including endogenous) expression levels, are highly dynamic, and selectively partition into the fibrillar center of nucleolus, with their formation, localization and liquid-like properties governed primarily by patterned charge blocks in its sequence. Importantly, correlative single-molecule tracking and condensates mapping reveal rRNA-modulated constrained mobility and spatiotemporally enriched chromatin-binding to rDNA for BRG1C specifically within nucleolar condensates. These findings unveil a condensation-mediated coupling between remodeler dynamics and nucleolar architecture, pointing to a potentially generic mechanism for organizing remodeling activity in both space and time.