Overlapping and non-overlapping roles of the class-I histone deacetylase-1 corepressors LET-418, SIN-3, and SPR-1 in Caenorhabditis elegans embryonic development

Background Histone 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. Objective To elucidate the functional relationships among the three transcriptional corepressors during embryogenesis. Methods The 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. 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. 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. 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.

Automated summary

The study revealed that the corepressors LET-418, SIN-3, and SPR-1 are crucial for embryonic development in Caenorhabditis elegans, playing similar roles in promoting progression to middle and late embryonic stages. Genetic interactions and gene ontology analysis indicated significant overlapping functions among SIN-3, SPR-1, and LET-418, as well as between SIN-3 and SPR-1. These findings suggest that the class-I HDAC-1 corepressors may cooperatively regulate gene expression levels or function independently within specific cells during C. elegans embryogenesis.