Abstract
The origin of eukaryotic histone modification enzymes still remains obscure. 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. Promiscuous aKMT4 could be regulated by chromatin environment. 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.
Highlights
The origin of eukaryotic histone modification enzymes still remains obscure
We show that a widespread lysine methyltransferase from Archaea, 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
A putative ribosomal protein L11 methyltransferase annotated in Sulfolobus genomes (NCBI entry YP_005648729, ORF SiRe-1449 as in S. islandicus REY15A, hereafter referred to as aKMT4) showed relatively high similarity to Dot1 from Saccharomyces cerevisiae
Summary
The origin of eukaryotic histone modification enzymes still remains obscure. Results: Prototypic KMT4/Dot from Archaea targets chromatin proteins (Sul7d and Cren7) and shows increased activity on Sul7d, but not Cren, in the presence of DNA. It has been proposed that this modification might have a direct or indirect effect on gene expression and thermal adaptation Supporting this idea, Cren is methylated at some of its 12 lysine residues, which may affect the chromatin structure [25]. We report that many Archaea, especially Crenarchaea, encode a lysine methyltransferase, which shows structural and enzymatic similarity to the eukaryotic KMT4/Dot family. We designated it as aKMT4 (belonging to the KMT4/Dot family of class I AdoMet-dependent MTases). Our data suggest that the activity of aKMT4 might be regulated by the local chromatin environment in Sulfolobus cells, albeit as a prototype of the KMT4/Dot family with extremely low sequence specificity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
