title: An evolutionarily 'young' lysine residue in histone H3 attenuates transcriptional output in Saccharomyces cerevisiae.
abstract: The DNA entry and exit points on the nucleosome core regulate the initial invasion of the nucleosome by factors requiring access to the underlying DNA. Here we describe in vivo consequences of eliminating a single protein-DNA interaction at this position through mutagenesis of histone H3 Lys 42 to alanine. This substitution has a dramatic effect on the Saccharomyces cerevisiae transcriptome in both the transcriptional output and landscape of mRNA species produced. We attribute this in part to decreased histone H3 occupancy at transcriptionally active loci, leading to enhanced elongation. Additionally we show that this lysine is methylated in vivo, and genetic studies of methyl-lysine mimics suggest that this modification may be crucial in attenuating gene expression. Interestingly, this site of methylation is unique to Ascomycota, suggesting a recent evolutionary innovation that highlights the evolvability of post-translational modifications of chromatin.
authors.affiliation: High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Edel M
authors.initials: EM
authors.lastname: Hyland
authors.forename: Henrik
authors.initials: H
authors.lastname: Molina
authors.forename: Kunal
authors.initials: K
authors.lastname: Poorey
authors.forename: Chunfa
authors.initials: C
authors.lastname: Jie
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xie
authors.forename: Junbiao
authors.initials: J
authors.lastname: Dai
authors.forename: Jiang
authors.initials: J
authors.lastname: Qian
authors.forename: Stefan
authors.initials: S
authors.lastname: Bekiranov
authors.forename: David T
authors.initials: DT
authors.lastname: Auble
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.forename: Jef D
authors.initials: JD
authors.lastname: Boeke
mesh_terms: D002843:Chromatin / Q000737:chemistry; D019175:DNA Methylation; D019143:Evolution, Molecular; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008239:Lysine / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism; D010445:Peptide Elongation Factors / Q000378:metabolism; D010641:Phenotype; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D009687:Nuclear Proteins; C097698:PAF1 protein, S cerevisiae; D010445:Peptide Elongation Factors; D029701:Saccharomyces cerevisiae Proteins; D008239:Lysine