title: The ankyrin repeats of G9a and GLP histone methyltransferases are mono- and dimethyllysine binding modules.
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.
authors.affiliation: Department of Biochemistry, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Collins
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Northrop
authors.forename: John R
authors.initials: JR
authors.lastname: Horton
authors.forename: David Y
authors.initials: DY
authors.lastname: Lee
authors.forename: Xing
authors.initials: X
authors.lastname: Zhang
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stallcup
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017089:Ankyrin Repeat; D019556:COS Cells; D002522:Chlorocebus aethiops; D011495:Histone-Lysine N-Methyltransferase / Q000737:chemistry* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding
chemical_list: D006657:Histones; D050505:Mutant Proteins; D010455:Peptides; C455847:EHMT1 protein, human; D008780:Methyltransferases; C533711:G9a protein, mouse; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine