Reference - Detail
| RRC ID | 88148 |
|---|---|
| Author | Osuma A, Destain H, Mann J, Li Y, Taylor SR, Prahlad M, Weigle IQ, Marques F, Schulz NG, Mathies LD, Islam P, Brown AEX, Smith JJ, Kratsios P. |
| Title | Cell type-specific functions of the PBAF chromatin-remodeling complex in neuronal diversification. |
| Journal | Nat Commun |
| Abstract |
Mutations in two highly related chromatin-remodeling complexes, BRG1/BRM-associated factor (BAF) and Polybromo-associated BAF (PBAF), 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, PBAF represses gene expression by antagonizing the terminal selector-type transcription factor UNC-3 (EBF1-4). In contrast, PBAF activates gene expression in caudal motor neurons. This dichotomy in PBAF function generates distinct motor neuron identities. PBAF disruption leads to locomotion defects. Genetic, genomic, and biochemical data suggest that the cell type-specific functions of PBAF in different motor neuron groups arise via its recruitment to specific gene loci by conserved transcription factors, such as MAB-9/TBX20. 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. |
| Volume | 17(1) |
| Pages | 741 |
| Published | 2025-12-14 |
| DOI | 10.1038/s41467-025-67434-9 |
| PII | 10.1038/s41467-025-67434-9 |
| PMID | 41390837 |
| PMC | PMC12820340 |
| MeSH | Animals Caenorhabditis elegans* / genetics Caenorhabditis elegans* / metabolism Caenorhabditis elegans Proteins* / genetics Caenorhabditis elegans Proteins* / metabolism Chromatin Assembly and Disassembly* / genetics Gene Expression Regulation, Developmental Motor Neurons* / cytology Motor Neurons* / metabolism Mutation Transcription Factors* / genetics Transcription Factors* / metabolism |
| Altmetric score |
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| The most frequently cited source | Bluesky |
| Total number of mentions | 1 |
| Altmetric score changes over past 6months | 0.2 |
| Resource | |
| C.elegans | tm4287 tm415 tm3647 |