title: A prototypic lysine methyltransferase 4 from archaea with degenerate sequence specificity methylates chromatin proteins Sul7d and Cren7 in different patterns.
abstract: BACKGROUND
  The origin of eukaryotic histone modification enzymes still remains obscure.
  
  
  RESULTS
  Prototypic KMT4/Dot1 from Archaea targets chromatin proteins (Sul7d and Cren7) and shows increased activity on Sul7d, but not Cren7, in the presence of DNA.
  
  
  CONCLUSIONS
  Promiscuous aKMT4 could be regulated by chromatin environment.
  
  
  CONCLUSIONS
  This study supports the prokaryotic origin model of eukaryotic histone methyltransferases and sheds light on chromatin dynamics in Archaea. Histone methylation is one of the major epigenetic modifications even in early diverging unicellular eukaryotes. We show that a widespread lysine methyltransferase from Archaea (aKMT4), bears striking structural and functional resemblance to the core of distantly related eukaryotic KMT4/Dot1. aKMT4 methylates a set of various proteins, including the chromatin proteins Sul7d and Cren7, and RNA exosome components. Csl4- and Rrp4-exosome complexes are methylated in different patterns. aKMT4 can self-methylate intramolecularly and compete with other proteins for the methyl group. Automethylation is inhibited by suitable substrates or DNA in a concentration-dependent manner. The automethylated enzyme shows relatively compromised activity. aKMT4-8A mutant with abrogated automethylation shows a more than 150% increase in methylation of substrates, suggesting a possible mechanism to regulate methyltransferase activity. More interestingly, methylation of Sul7d, but not Cren7, by aKMT4 is significantly enhanced by DNA. MS/MS and kinetic analysis further suggest that aKMT4 methylates Sul7d in the chromatin context. These data provide a clue to the possible regulation of aKMT4 activity by the local chromatin environment, albeit as a promiscuous enzyme required for extensive and variegated lysine methylation in Sulfolobus. This study supports the prokaryotic origin model of eukaryotic histone modification enzymes and sheds light on regulation of archaeal chromatin.
authors.affiliation: State Key Laboratory of Agro-Biotechnology and Ministry of Agriculture Key Laboratory of Soil Microbiology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Niu
authors.forename: Yisui
authors.initials: Y
authors.lastname: Xia
authors.forename: Sishuo
authors.initials: S
authors.lastname: Wang
authors.forename: Jiani
authors.initials: J
authors.lastname: Li
authors.forename: Caoyuan
authors.initials: C
authors.lastname: Niu
authors.forename: Xiao
authors.initials: X
authors.lastname: Li
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Zhao
authors.forename: Huiyang
authors.initials: H
authors.lastname: Xiong
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Lou
authors.forename: Qinhong
authors.initials: Q
authors.lastname: Cao
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D019843:Archaeal Proteins / Q000737:chemistry* / Q000235:genetics; D002843:Chromatin / Q000737:chemistry; D017124:Conserved Sequence; D019641:DNA, Archaeal / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000737:chemistry*; D008745:Methylation; D008969:Molecular Sequence Data; D011496:Protein Methyltransferases / Q000737:chemistry* / Q000235:genetics; D011499:Protein Processing, Post-Translational; D013379:Substrate Specificity; D016944:Sulfolobus / Q000201:enzymology*
chemical_list: D019843:Archaeal Proteins; D002843:Chromatin; D019641:DNA, Archaeal; D004268:DNA-Binding Proteins; D011496:Protein Methyltransferases
keywords: Archaea; Chromatin Modification; DNA-binding Protein; Histone Methylation; Protein Methylation