ATP-dependent chromatin remodeler SMARCA4 (BRG1)

BRG1 (Brahma-related gene 1; SMARCA4) is the catalytic ATPase subunit of the SWI/SNF chromatin remodeling complex, a large multiprotein assembly that regulates transcription by altering chromatin structure[1][2][3]. Through ATP-driven nucleosome repositioning, BRG1 plays essential roles in both activating and repressing gene expression. It is indispensable for development and cell differentiation, including neural, eye, smooth muscle, sperm, and cardiac development[1][2]. In cancer, BRG1 acts as both tumor suppressor and facilitator of malignant transformation depending on context, and is frequently inactivated via missense mutations[1][3]. Clinically, BRG1 status informs prognosis and is being explored as a therapeutic target, though safety concerns remain due to its fundamental role in cell biology. Drugs such as darinaparsin may target BRG1, and loss or mutation of BRG1 confers distinct biological responses, including chemotherapy resistance in several tumor types[1].

Other names

Brahma-related gene 1BRG1SMARCA4Transcription activator BRG1ATP-dependent chromatin remodeler SMARCA4

Drugs may interfere with BRG1’s association with chromatin, leading to exclusion from DNA and altered gene expression (e.g., darinaparsin-driven phosphorylation and chromatin exclusion) Modulation of nuclear receptor function via chromatin remodeling Alteration of gene expression programs sustaining undifferentiated or tumorigenic states