RRC ID 51543
著者 De Stasio EA, Mueller KP, Bauer RJ, Hurlburt AJ, Bice SA, Scholtz SL, Phirke P, Sugiaman-Trapman D, Stinson LA, Olson HB, Vogel SL, Ek-Vazquez Z, Esemen Y, Korzynski J, Wolfe K, Arbuckle BN, Zhang H, Lombard-Knapp G, Piasecki BP, Swoboda P.
タイトル An Expanded Role for the RFX Transcription Factor DAF-19, with Dual Functions in Ciliated and Nonciliated Neurons.
ジャーナル Genetics
Abstract Regulatory Factor X (RFX) transcription factors (TFs) are best known for activating genes required for ciliogenesis in both vertebrates and invertebrates. In humans, eight RFX TFs have a variety of tissue-specific functions, while in the worm Caenorhabditis elegans, the sole RFX gene, daf-19, encodes a set of nested isoforms. Null alleles of daf-19 confer pleiotropic effects including altered development with a dauer constitutive phenotype, complete absence of cilia and ciliary proteins, and defects in synaptic protein maintenance. We sought to identify RFX/daf-19 target genes associated with neuronal functions other than ciliogenesis using comparative transcriptome analyses at different life stages of the worm. Subsequent characterization of gene expression patterns revealed one set of genes activated in the presence of DAF-19 in ciliated sensory neurons, whose activation requires the daf-19c isoform, also required for ciliogenesis. A second set of genes is downregulated in the presence of DAF-19, primarily in nonsensory neurons. The human orthologs of some of these neuronal genes are associated with human diseases. We report the novel finding that daf-19a is directly or indirectly responsible for downregulation of these neuronal genes in C. elegans by characterizing a new mutation affecting the daf-19a isoform (tm5562) and not associated with ciliogenesis, but which confers synaptic and behavioral defects. Thus, we have identified a new regulatory role for RFX TFs in the nervous system. The new daf-19 candidate target genes we have identified by transcriptomics will serve to uncover the molecular underpinnings of the pleiotropic effects that daf-19 exerts on nervous system function.
巻・号 208(3)
ページ 1083-1097
公開日 2018-3-1
DOI 10.1534/genetics.117.300571
PII genetics.117.300571
PMID 29301909
PMC PMC5844324
MeSH Alleles Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Gene Expression Profiling Gene Expression Regulation Genes, Reporter Humans Neurons / metabolism* Protein Binding Regulatory Factor X1 / metabolism* Transcription Factors / metabolism* Transcriptional Activation Transcriptome
IF 4.015
引用数 2
リソース情報
線虫 tm5562