Abstract
BackgroundHistone deacetylase (HDAC)-1, a Class-I HDAC family member, forms three types of complexes, the nucleosome remodeling deacetylase, Sin3, and CoREST complexes with the specific corepressor components chromodomain-helicase-DNA-binding protein 3 (Mi2/CHD-3), Sin3, and REST corepressor 1 (RCOR1), respectively, in humans.ObjectiveTo elucidate the functional relationships among the three transcriptional corepressors during embryogenesis.MethodsThe activities of HDA-1, LET-418, SIN-3, and SPR-1, the homologs of HDAC-1, Mi2, Sin3, and RCOR1 in Caenorhabditis elegans during embryogenesis were investigated through measurement of relative mRNA expression levels and embryonic lethality given either gene knockdown or deletion. Additionally, the terminal phenotypes of each knockdown and mutant embryo were observed using a differential-interference contrast microscope. Finally, the functional relationships among the three corepressors were examined through genetic interactions and transcriptome analyses.ResultsHere, we report that each of the corepressors LET-418, SIN-3, and SPR-1 are expressed and have essential roles in C. elegans embryonic development. Our terminal phenotype observations of single mutants further implied that LET-418, SIN-3, and SPR-1 play similar roles in promoting advancement to the middle and late embryonic stages. Combined analysis of genetic interactions and gene ontology of these corepressors indicate a prominent overlapping role among SIN-3, SPR-1, and LET-418 and between SIN-3 and SPR-1.ConclusionOur findings suggest that the class-I HDAC-1 corepressors LET-418, SIN-3, and SPR-1 may cooperatively regulate the expression levels of some genes during C. elegans embryogenesis or may have some similar roles but functioning independently within a specific cell.
Highlights
During embryonic development, daughter cells generated from fertilized eggs contain the same genomic information as the progenitor cells when the cell division process is completed
Similar to previous findings indicating that extracellular matrix (ECM) genes are upregulated in hda-1(RNAi) embryos (Whetstine et al 2005), we found that genes encoding ECM- and ECM-related mRNAs are significantly upregulated in the C. elegans Histone deacetylase (HDAC)-1 corepressor mutants, let-418(n3536), sin-3(tm1276), and spr-1(ok2144)
Using combined analyses of genetic interactions and transcriptome levels, we identified the overlapping functions among the C. elegans homologs of the HDAC-1 corepressors, LET-418, SIN-3, and SPR-1
Summary
Daughter cells generated from fertilized eggs contain the same genomic information as the progenitor cells when the cell division process is completed They have identical genome sequences, daughter cells can differentiate from precursor cells within developing tissues and organs through the epigenomic control of gene expression. Results Here, we report that each of the corepressors LET-418, SIN-3, and SPR-1 are expressed and have essential roles in C. elegans embryonic development. Our terminal phenotype observations of single mutants further implied that LET-418, SIN-3, and SPR-1 play similar roles in promoting advancement to the middle and late embryonic stages. Conclusion Our findings suggest that the class-I HDAC-1 corepressors LET-418, SIN-3, and SPR-1 may cooperatively regulate the expression levels of some genes during C. elegans embryogenesis or may have some similar roles but functioning independently within a specific cell
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