GBAF, a small BAF sub-complex with big implications: a systematic review

Abstract

ATP-dependent chromatin remodeling by histone-modifying enzymes and chromatin remodeling complexes is crucial for maintaining chromatin organization and facilitating gene transcription. In the SWI/SNF family of ATP-dependent chromatin remodelers, distinct complexes such as BAF, PBAF, GBAF, esBAF and npBAF/nBAF are of particular interest regarding their implications in cellular differentiation and development, as well as in various diseases. The recently identified BAF subcomplex GBAF is no exception to this, and information is emerging linking this complex and its components to crucial events in mammalian development. Furthermore, given the essential nature of many of its subunits in maintaining effective chromatin remodeling function, it comes as no surprise that aberrant expression of GBAF complex components is associated with disease development, including neurodevelopmental disorders and numerous malignancies. It becomes clear that building upon our knowledge of GBAF and BAF complex function will be essential for advancements in both mammalian reproductive applications and the development of more effective therapeutic interventions and strategies. Here, we review the roles of the SWI/SNF chromatin remodeling subcomplex GBAF and its subunits in mammalian development and disease.

The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasion in vivo

“…Though many SWI/SNF assemblies have been described in mammalian and other systems, including BAF, PBAF, esBAF, GBAF, nBAF, and npBAF [53], to date, BAF and PBAF are the only SWI/SNF assemblies that have been described in C. elegans. Both assemblies consist of core subunits (SWSN-1, SWSN-4, SWSN-5) and accessory subunits (DPFF-1, SWSN-2.1/ HAM-3, SWSN-2.2, SWSN-3, SWSN-6, and PHF-10), collectively referred to as common factors [47,54].…”

The SWI/SNF chromatin remodeling assemblies BAF and PBAF differentially regulate cell cycle exit and cellular invasionin vivo

“…Though many SWI/SNF assemblies have been described in mammalian and other systems, including BAF, PBAF, esBAF, GBAF, nBAF, and npBAF) (53), to date, BAF and PBAF are the only SWI/SNF assemblies that have been described in C. elegans . Both assemblies consist of core subunits (SWSN-1, SWSN-4, SWSN-5) and accessory subunits (DPFF-1, SWSN-2.1/HAM-3, SWSN-2.2, SWSN-3, SWSN-6, and PHF-10), collectively referred to as common factors (46,54).…”

Multi-omic analysis of CIC’s functional networks reveals novel interaction partners and a potential role in mitotic fidelity

“…GLTSCR1 has only recently been identified as a member of the GBAF SWI/SNF complex (Alpsoy and Dykhuizen 2018), and thus GLTSCR1’s role as a SWI/SNF subunit is not fully understood. Notably, knockdown of another GBAF subunit member, SMARCA4, was shown to reduce cell proliferation and induce cell cycle arrest (Innis and Cabot 2020; Giles et al 2021), a role that may be shared by other GBAF members. Within the 88 co-essential genes, we found a significant enrichment for genes with functions related to regulation of attachment of spindle microtubules to kinetochores (BECNI and SIRT2’ , BH-adjusted p-value = 0.0015) and regulation of exit from mitosis (TGFB1 and SIRT2- , BH-adjusted p-value = 0.0031; Figure 4b; Supplemental Table S5; Methods).…”