title: Lysyl 5-hydroxylation, a novel histone modification, by Jumonji domain containing 6 (JMJD6).
abstract: JMJD6 is reported to hydroxylate lysyl residues of a splicing factor, U2AF65. In this study, we found that JMJD6 hydroxylates histone lysyl residues. In vitro experiments showed that JMJD6 has a binding affinity to histone proteins and hydroxylates multiple lysyl residues of histone H3 and H4 tails. Using JMJD6 knock-out mouse embryos, we revealed that JMJD6 hydroxylates lysyl residues of histones H2A/H2B and H3/H4 in vivo by amino acid composition analysis. 5-Hydroxylysine was detected at the highest level in histones purified from murine testis, which expressed JMJD6 at a significantly high level among various tissues examined, and JMJD6 overexpression increased the amount of 5-hydroxylysine in histones in human embryonic kidney 293 cells. These results indicate that histones are additional substrates of JMJD6 in vivo. Because 5-hydroxylation of lysyl residues inhibited N-acetylation and N-methylation by an acetyltransferase and a methyltransferase, respectively, in vitro, histone 5-hydroxylation may have important roles in epigenetic regulation of gene transcription or chromosomal rearrangement.
authors.affiliation: Division of Epigenetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Motoko
authors.initials: M
authors.lastname: Unoki
authors.forename: Akiko
authors.initials: A
authors.lastname: Masuda
authors.forename: Naoshi
authors.initials: N
authors.lastname: Dohmae
authors.forename: Kyohei
authors.initials: K
authors.lastname: Arita
authors.forename: Masanori
authors.initials: M
authors.lastname: Yoshimatsu
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Iwai
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fukui
authors.forename: Koji
authors.initials: K
authors.lastname: Ueda
authors.forename: Ryuji
authors.initials: R
authors.lastname: Hamamoto
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shirakawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
mesh_terms: D000107:Acetylation; D000818:Animals; D033481:Chromosomes, Mammalian / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006900:Hydroxylation / Q000502:physiology; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008745:Methylation; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D013737:Testis / Q000201:enzymology; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D006657:Histones; C498707:JMJD6 protein, human; D056484:Jumonji Domain-Containing Histone Demethylases; D008239:Lysine