RRC ID 46356
著者 Shan CM, Wang J, Xu K, Chen H, Yue JX, Andrews S, Moresco JJ, Yates JR, Nagy PL, Tong L, Jia S.
タイトル A histone H3K9M mutation traps histone methyltransferase Clr4 to prevent heterochromatin spreading.
ジャーナル Elife
Abstract Histone lysine-to-methionine (K-to-M) mutations are associated with multiple cancers, and they function in a dominant fashion to block the methylation of corresponding lysines on wild type histones. However, their mechanisms of function are controversial. Here we show that in fission yeast, introducing the K9M mutation into one of the three histone H3 genes dominantly blocks H3K9 methylation on wild type H3 across the genome. In addition, H3K9M enhances the interaction of histone H3 tail with the H3K9 methyltransferase Clr4 in a SAM (S-adenosyl-methionine)-dependent manner, and Clr4 is trapped at nucleation sites to prevent its spreading and the formation of large heterochromatin domains. We further determined the crystal structure of an H3K9M peptide in complex with human H3K9 methyltransferase G9a and SAM, which reveales that the methionine side chain had enhanced van der Waals interactions with G9a. Therefore, our results provide a detailed mechanism by which H3K9M regulates H3K9 methylation.
巻・号 5
公開日 2016-9-20
DOI 10.7554/eLife.17903
PII e17903
PMID 27648579
PMC PMC5030085
MeSH Amino Acid Substitution* Cell Cycle Proteins / metabolism* Crystallography, X-Ray Heterochromatin / metabolism* Histone-Lysine N-Methyltransferase Histones / chemistry Histones / genetics* Histones / metabolism* Humans Lysine / genetics Lysine / metabolism Methionine / genetics Methionine / metabolism Methyltransferases / metabolism* Models, Molecular Protein Conformation Schizosaccharomyces / genetics* Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / metabolism*
IF 7.08
引用数 16
リソース情報
酵母 genomic DNA library (pTN-L1)