Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3 HDAC complex

Flore Beurton; Przemysław Stempor; Matthieu J. Caron; Alex Appert; Dong Yan; Ron A.-J. Chen; David Cluet; Yohann Couté; Marion Herbette; Ni Huang; Hélène Polvèche; Martin Spichty; Cécile Bedet; Julie Ahringer; Francesca Palladino

doi:10.1093/nar/gkz880

GenomicsNucleic Acids ResearchOct 3, 2019

Peer-reviewed journal article

Physical and functional interaction between SET1/COMPASS complex component CFP-1 and a Sin3 HDAC complex

Flore Beurton, Przemysław Stempor iD, Matthieu J. Caron iD, Alex Appert, Dong Yan iD, Ron A.-J. Chen iD, David Cluet iD, Yohann Couté iD, Marion Herbette iD, Ni Huang iD, Hélène Polvèche iD, Martin Spichty iD, Cécile Bedet iD, Julie Ahringer iD, Francesca Palladino iD

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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 Ly4 (H3K4me3). Although H3K4me3 is widely associated with gene expression, the effects of CFP1 loss depend on chromatin context, so it is important to understand the relationship between CFP1 and other chromatin factors. Using a proteomics approach, we identified an unexpected link between C. elegans CFP-1 and a Rpd3/Sin3 histone deacetylase complex. We find that mutants of CFP-1, SIN-3, and the catalytic subunit SET-2/SET1 have similar phenotypes and misregulate 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 Sin3 HDAC complex at promoters and uncover coordinate regulation of gene expression by chromatin complexes having distinct activities.