| RRC ID |
88148
|
| 著者 |
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.
|
| タイトル |
Cell type-specific functions of the PBAF chromatin-remodeling complex in neuronal diversification.
|
| ジャーナル |
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.
|
| 巻・号 |
17(1)
|
| ページ |
741
|
| 公開日 |
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
|
| リソース情報 |
| 線虫 |
tm4287
tm415
tm3647 |
