A Prototypic Lysine Methyltransferase 4 from Archaea with Degenerate Sequence Specificity Methylates Chromatin Proteins Sul7d and Cren7 in Different Patterns

摘要: 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 core distantly related eukaryotic KMT4/Dot1. aKMT4 methylates set various proteins, including chromatin proteins Sul7d Cren7, RNA exosome components. Csl4- Rrp4-exosome complexes are methylated different patterns. can self-methylate intramolecularly compete with other for methyl group. Automethylation inhibited by suitable substrates or DNA concentration-dependent manner. The automethylated enzyme shows relatively compromised activity. aKMT4-8A mutant abrogated automethylation more than 150% increase substrates, suggesting possible mechanism regulate More interestingly, Sul7d, but not significantly enhanced DNA. MS/MS kinetic analysis further suggest context. These data provide clue regulation activity local environment, albeit as promiscuous required extensive variegated Sulfolobus. This study supports prokaryotic origin model histone modification enzymes sheds light on archaeal chromatin.