Work

Cell type-specific functions of the PBAF chromatin-remodeling complex in neuronal diversification

Year: 2025

Type: article

Abstract: The mammalian SWI/SNF family of chromatin remodelers includes the BAF and PBAF complexes, mutations in which cause various neurodevelopmental conditions. Although BAF activity is required at multiple steps of nervous system development, the specific neural functions of PBAF remain largely unexplored. Through an unbiased genetic screen in C. elegans, we identify here critical roles for PBAF in postmitotic neuronal identity. In nerve cord motor neurons (MNs), PBAF represses gene expression by antagonizing the terminal selector-type transcription factor UNC-3 (EBF1-4). In contrast, PBAF activates gene expression in posteriorly located MNs. This dichotomy in PBAF function generates distinct MN identities. Genetic evidence suggests that the cell type-specific functions of PBAF in different MN groups arise via its recruitment to specific gene loci by conserved transcription factors. Altogether, our findings provide a conceptual framework to understand specific neuronal defects that arise in neurological conditions caused by mutations in broadly expressed chromatin-remodeling complexes.

Source: Nature Communications

DOI: 10.1038/s41467-025-67434-9