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.

Keywords: Chromatin remodeling; Embryonic development; Epigenetic modification; Gene expression; Neurodevelopment; Oncogene; Pluripotency; Tumor suppressor.

Fig. 1

Schematic representation of chromatin arrangement. a Double stranded DNA (dsDNA) forms the genetic material. b dsDNA wraps around a histone octamer, forming a nucleosome. c Nucleosomes form the repeating organizational units of chromatin. d Condensation of looped chromatin forms chromatin fibers. e Further compaction of chromatin fibers forms chromatids and, ultimately, chromosomes. Figure created using BioRender.com

Fig. 2

Schematic representations of the BAF, PBAF, GBAF, esBAF, npBAF, and nBAF complexes. Gray subunits are shared across multiple complexes. Gray subunits are general BAF-subcomplex components, yellow subunits are BAF-specific, blue subunits are PBAF-specific, orange subunits are GBAF-specific, the red subunit is esBAF-specific, and the green subunits are nBAF-specific following npBAF/nBAF switching. Subunits with two colors indicate that a subunit could be a defining component from either represented complex

Fig. 3

Heatmap representing the frequency of mutated GBAF subunits in each TCGA cancer type. Color indicates frequency of mutated subunit in each cancer type. Study data provided by [193, 194] are represented. Data obtained from cBioPortal

Fig. 4

Stacked bar chart showing the number of GBAF subunit mutations across The Cancer Genome Atlas (TCGA) study data obtained from cBioPortal. Study data provided by [193, 194] are represented. Color indicates mutation type