Brg1

Brg1, also known as Brahma-related gene 1, is an ATP-dependent chromatin remodeling factor encoded by the SMARCA4 gene in humans. It serves as one of the catalytic subunits of the SWI/SNF chromatin remodeling complexes, which regulate access to DNA by repositioning nucleosomes using energy from ATP hydrolysis.

BRG1 is a nuclear protein that forms part of SWI/SNF subcomplexes such as BAF and PBAF. The protein contains a helicase/ATPase domain responsible for remodeling activity and a bromodomain that recognizes acetylated histones, helping target BRG1-containing complexes to regulatory regions of the genome. Through remodeling of chromatin, BRG1 influences the expression of many genes in response to developmental cues and environmental signals.

Biological roles of BRG1 are broad and include regulation of development, cellular differentiation, and maintenance of genome stability. BRG1 activity is important for embryonic development and for the proper expression programs that drive lineage specification, cell cycle control, and DNA damage responses. Its function is context-dependent and involves interactions with a wide network of transcription factors and other chromatin regulators.

Clinical significance of BRG1 relates largely to cancer and developmental disorders. Mutations or loss of SMARCA4/BRG1 occur in several cancers and are associated with specific tumor subtypes and poor prognosis in some contexts. In tumors where BRG1 is inactivated, the SWI/SNF pathway often becomes a therapeutic vulnerability, and research is ongoing into targeted strategies that exploit these defects.

BRG1 is broadly conserved among eukaryotes and is expressed in many tissues. Multiple BRG1 isoforms exist, produced by alternative splicing, which may modulate its regulatory interactions and remodeling activity.