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E-GEOD-40127 - GEI-8, a homologue of vertebrate nuclear receptor corepressor NCoR/SMRT, regulates development and neuronal functions in C. elegans

Status
Released on 11 August 2013, last updated on 30 September 2015
Organism
Caenorhabditis elegans
Samples (6)
Array (1)
Protocols (7)
Description
NCoR and SMRT are two paralogous vertebrate proteins that function as corepressors with unliganded nuclear receptors. Although C. elegans has a large number of nuclear receptors, orthologues of the corepressors NCoR and SMRT have not unambiguously been identified in Drosophila or C. elegans. Here, we identify GEI-8 as the closest homologue of NCoR and SMRT in C. elegans and demonstrate that GEI-8 is expressed as at least two isoforms throughout development in multiple tissues, including neurons, muscle and intestinal cells. We demonstrate that a homozygous deletion within the gei-8 coding region, which is predicted to encode a truncated protein lacking the predicted NR domain, results in severe mutant phenotypes with developmental defects, slow movement and growth, arrested gonadogenesis and defects in cholinergic neurotransmission. Whole genome expression analysis by microarrays identified sets of de-regulated genes consistent with both the observed mutant phenotypes and a role of GEI-8 in regulating transcription. Interestingly, the upregulated transcripts included a predicted mitochondrial sulfide:quinine reductase encoded by Y9C9A.16. This locus also contains non-coding, 21-U RNAs of the piRNA. Inhibition of the expression of the region coding for 21-U RNAs leads to irregular gonadogenesis in the homozygous gei-8 mutants, but not in an otherwise wild-type background, suggesting that GEI-8 may function in concert with the 21-U RNAs to regulate gonadogenesis. Our results confirm that GEI-8 is the orthologue of the vertebrate NCoR/SMRT corepressors and demonstrate important roles for this putative transcriptional corepressor in development and neuronal function. Comparison of Mutant vs. WT control with three replications per treatment group
Experiment type
transcription profiling by array 
Contacts
WeiPing Chen <weipingChen@niddk.nih.gov>, Johana Kollarova, Katerina Sebkova, Marta Kostrouchova, Michael W Krause, Pavol Mikolas, Vladimir Saudek, Zdenek Kostrouch
Citation
GEI-8, a homologue of vertebrate nuclear receptor corepressor NCoR/SMRT, regulates gonad development and neuronal functions in Caenorhabditis elegans. Mikoláš P, Kollárová J, Sebková K, Saudek V, Yilma P, Kostrouchová M, Krause MW, Kostrouch Z, Kostrouchová M. , PMID:23484030
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-40127.idf.txt
Sample and data relationshipE-GEOD-40127.sdrf.txt
Raw data (1)E-GEOD-40127.raw.1.zip
Processed data (1)E-GEOD-40127.processed.1.zip
Array designA-AFFY-60.adf.txt
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