Bromodomain-containing protein 9-containing non-canonical BAF (ncBAF) chromatin-remodeling complex (ncBAF)

The Bromodomain-containing protein 9-containing non-canonical BAF (ncBAF) chromatin-remodeling complex, also known as GBAF, is a specialized assembly of the SWI/SNF family (Alpsoy & Dykhuizen, 2018, Nature Communications). It is uniquely defined by the inclusion of the BRD9 and GLTSCR1/1L subunits, while lacking the SMARCB1 and ARID subunits found in canonical BAF complexes (Michel et al., 2018, Nature). Biologically, the ncBAF complex regulates gene expression by modulating chromatin accessibility, specifically targeting CTCF-binding sites and promoters to maintain cellular identity (Mashtalir et al., 2018, Cell). In the context of disease, ncBAF becomes a critical dependency in certain cancers, such as synovial sarcoma (driven by the SS18-SSX fusion) and SMARCB1-deficient rhabdoid tumors, where it supports oncogenic transcriptional programs (Brien et al., 2018, eLife). Therapeutic targeting of this complex focuses on the BRD9 subunit, utilizing small-molecule inhibitors or PROTAC degraders to disrupt the complex's assembly or function (Remillard et al., 2017, Angewandte Chemie). These interventions aim to reverse aberrant epigenetic states and inhibit tumor growth, with several candidates like FHD-609 and CFT8634 currently in clinical and preclinical development (Foghorn Therapeutics, 2023; C4 Therapeutics, 2023). The specificity of BRD9 for the ncBAF complex makes it an attractive target for precision oncology in SWI/SNF-mutant malignancies.

Other names

GBAF complexGLTSCR1/GLTSCR1L-BAF complexNon-canonical BAF complexBRD9-BAF complex

Targeted protein degradation (PROTAC) of the BRD9 subunit or small-molecule inhibition of the BRD9 bromodomain to disrupt the assembly and genomic recruitment of the ncBAF complex, thereby inhibiting oncogenic gene expression (Remillard et al., 2017, Angewandte Chemie; Brien et al., 2018, eLife).