title: Histone H3 tail clipping regulates gene expression.
abstract: Induction of gene expression in yeast and human cells involves changes in the histone modifications associated with promoters. Here we identify a histone H3 endopeptidase activity in Saccharomyces cerevisiae that may regulate these events. The endopeptidase cleaves H3 after Ala21, generating a histone that lacks the first 21 residues and shows a preference for H3 tails carrying repressive modifications. In vivo, the H3 N terminus is clipped, specifically within the promoters of genes following the induction of transcription. H3 clipping precedes the process of histone eviction seen when genes become fully active. A truncated H3 product is not generated in yeast carrying a mutation of the endopeptidase recognition site (H3 Q19A L20A) and gene induction is defective in these cells. These findings identify clipping of H3 tails as a previously uncharacterized modification of promoter-bound nucleosomes, which may result in the localized clearing of repressive signals during the induction of gene expression.
authors.affiliation: Gurdon Institute and Department of Pathology, Tennis Court Road, Cambridge CB2 1QN, UK.
authors.forename: Helena
authors.initials: H
authors.lastname: Santos-Rosa
authors.forename: Antonis
authors.initials: A
authors.lastname: Kirmizis
authors.forename: Christopher
authors.initials: C
authors.lastname: Nelson
authors.forename: Till
authors.initials: T
authors.lastname: Bartke
authors.forename: Nehme
authors.initials: N
authors.lastname: Saksouk
authors.forename: Jacques
authors.initials: J
authors.lastname: Cote
authors.forename: Tony
authors.initials: T
authors.lastname: Kouzarides
mesh_terms: D010450:Endopeptidases / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D006657:Histones / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012331:RNA, Fungal / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D012331:RNA, Fungal; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D010450:Endopeptidases; C021361:histone proteases