GSE110072
Physical and functional interaction between the SET1 complex component CFP-1/CXXC and the Sin-3S/HDAC complex in C. elegans embryos
The highly conserved CFP1 CXXC zinc finger protein targets SET1 family complexes to promoter regions to implement methylation of histone H3 Ly4  (H3K4me), a mark that correlates with gene expression  depending on the chromatin context. Whether CFP1 physically interacts with additional chromatin modifying proteins on chromatin has not been investigated. By applying interaction proteomics coupled to mass spectrometry to identify factors that interact with C. elegans CFP-1, we establish a link between CFP-1 and the Rpd3/Sin3 histone deacetylase (HDAC) small complex (Rpd3/Sin3S) in embryos. We show that CFP-1 directly interacts with SIN-3 through a highly conserved C-terminal domain, and that the two proteins extensively colocalize with H3K4me3 at promoter regions genome-wide. Animals lacking sin-3, cfp-1 or the catalytic H3K4 methyltransferase subunit set-2/SET1 show misregulation of common genes in early embryos, reduction in fertility, and defects in the division of intestinal cells in adults, consistent with common developmental functions. Our results suggest that in addition to its well characterized role as a central subunit of the SET-2/SET1 complex, CFP-1 interacts with the Sin3S/HDAC complex at promoter regions to influence gene expression in a developmental context. This has implications for the coordinate regulation of gene expression by chromatin associated complexes with distinct activities. Overall design: 3 replicates of 4 different embryonic C.elegans strains have been anayzed : wild-type strain (WT) was used as control and the 3 mutants strains are cfp-1(tm6369), sin-3(tm1276) and set-2(bn129)