Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3S HDAC complex in C. elegans

Nucleic Acids Res. 2019 Dec 2;47(21):11164-11180. doi: 10.1093/nar/gkz880.

Abstract

The CFP1 CXXC zinc finger protein targets the SET1/COMPASS complex to non-methylated CpG rich promoters to implement tri-methylation of histone H3 Lys4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss vary, suggesting additional chromatin factors contribute to context dependent effects. Using a proteomics approach, we identified CFP1 associated proteins and an unexpected direct link between Caenorhabditis elegans CFP-1 and an Rpd3/Sin3 small (SIN3S) histone deacetylase complex. Supporting a functional connection, we find that mutants of COMPASS and SIN3 complex components genetically interact and have similar phenotypic defects including misregulation of common genes. CFP-1 directly binds SIN-3 through a region including the conserved PAH1 domain and recruits SIN-3 and the HDA-1/HDAC subunit to H3K4me3 enriched promoters. Our results reveal a novel role for CFP-1 in mediating interaction between SET1/COMPASS and a Sin3S HDAC complex at promoters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / embryology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / metabolism
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Embryo, Nonmammalian
  • Histone-Lysine N-Methyltransferase / metabolism*
  • Histone-Lysine N-Methyltransferase / physiology
  • Multiprotein Complexes / metabolism
  • Multiprotein Complexes / physiology*
  • Protein Binding
  • Sin3 Histone Deacetylase and Corepressor Complex / metabolism*
  • Trans-Activators / metabolism*

Substances

  • Caenorhabditis elegans Proteins
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Trans-Activators
  • cfp-1 protein, C elegans
  • Histone-Lysine N-Methyltransferase
  • Set-1 protein, C elegans
  • Sin3 Histone Deacetylase and Corepressor Complex