RRC ID 59448
著者 Brandt JP, Rossillo M, Du Z, Ichikawa D, Barnes K, Chen A, Noyes M, Bao Z, Ringstad N.
タイトル Lineage context switches the function of a C. elegans Pax6 homolog in determining a neuronal fate.
ジャーナル Development
Abstract The sensory nervous system of C. elegans comprises cells with varied molecular and functional characteristics, and is, therefore, a powerful model for understanding mechanisms that generate neuronal diversity. We report here that VAB-3, a C. elegans homolog of the homeodomain-containing protein Pax6, has opposing functions in regulating expression of a specific chemosensory fate. A homeodomain-only short isoform of VAB-3 is expressed in BAG chemosensory neurons, where it promotes gene expression and cell function. In other cells, a long isoform of VAB-3, comprising a Paired homology domain and a homeodomain, represses expression of ETS-5, a transcription factor required for expression of BAG fate. Repression of ets-5 requires the Eyes Absent homolog EYA-1 and the Six-class homeodomain protein CEH-32. We determined sequences that mediate high-affinity binding of ETS-5, VAB-3 and CEH-32. The ets-5 locus is enriched for ETS-5-binding sites but lacks sequences that bind VAB-3 and CEH-32, suggesting that these factors do not directly repress ets-5 expression. We propose that a promoter-selection system together with lineage-specific expression of accessory factors allows VAB-3/Pax6 to either promote or repress expression of specific cell fates in a context-dependent manner. This article has an associated 'The people behind the papers' interview.
巻・号 146(8)
公開日 2019-4-15
DOI 10.1242/dev.168153
PII dev.168153
PMID 30890567
PMC PMC6503985
MeSH Animals Antineoplastic Combined Chemotherapy Protocols / metabolism Bleomycin / metabolism Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Chlorambucil / metabolism Cisplatin / metabolism Cyclophosphamide / metabolism Dactinomycin / metabolism Gene Expression Regulation, Developmental / genetics Homeodomain Proteins / genetics Homeodomain Proteins / metabolism* Intracellular Signaling Peptides and Proteins / genetics Intracellular Signaling Peptides and Proteins / metabolism Neurons / cytology Neurons / metabolism Nuclear Proteins / genetics Nuclear Proteins / metabolism Promoter Regions, Genetic / genetics Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / metabolism Proto-Oncogene Proteins c-ets / genetics Proto-Oncogene Proteins c-ets / metabolism Transcription Factors / genetics Transcription Factors / metabolism* Vinblastine / metabolism
IF 5.763
引用数 2
リソース情報
線虫 tm1734