The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules

• Type of Material: Article
• Authors: Robert E Collins, Emory University; Jeffrey P Northrop, Norris Comprehensive Cancer Center; John Horton, Emory University; David Y Lee, Norris Comprehensive Cancer Center; Xing Zhang, Emory University; Michael R Stallcup, Norris Comprehensive Cancer Center; Xiaodong Cheng, Emory University
• Language: English
• Date: 2008-03
• Publisher: Nature Research (part of Springer Nature)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2008, Rights Managed by Nature Publishing Group
• Final Published Version (URL): http://www.nature.com/nsmb/journal/v15/n3/full/nsmb.1384.html
• Title of Journal or Parent Work: Nature Structural and Molecular Biology
• ISSN: 1545-9993
• Volume: 15
• Issue: 3
• Start Page: 245
• End Page: 250
• Grant/Funding Information: This work was supported by grants DK55274 to M.R.S. and GM068680 to X.C. from the US National Institutes of Health.
• Research Categories: Chemistry, Biochemistry; Biology, Molecular

Abstract

Histone modifications have important roles in transcriptional control, mitosis and heterochromatin formation. G9a and G9a-like protein (GLP) are euchromatin-associated methyltransferases that repress transcription by mono- and dimethylating histone H3 at Lys9 (H3K9). Here we demonstrate that the ankyrin repeat domains of G9a and GLP bind with strong preference to N-terminal H3 peptides containing mono- or dimethyl K9. X-ray crystallography revealed the basis for recognition of the methylated lysine by a partial hydrophobic cage with three tryptophans and one acidic residue. Substitution of key residues in the cage eliminated the H3 tail interaction. Hence, G9a and GLP contain a new type of methyllysine binding module (the ankyrin repeat domains) and are the first examples of protein (histone) methyltransferases harboring in a single polypeptide the activities that generate and read the same epigenetic mark.