title: Histone cross-linking by transglutaminase.
abstract: Transglutaminases irreversibly catalyze covalent cross-linking of proteins by forming isopeptide bonds between peptide-bound glutamine and lysine residues. Among several transglutaminases, tissue-type transglutaminase (tTGase) is most ubiquitously found in every type of cells and tissues in animals, but its natural substrate has yet to be identified. In an attempt to identify the natural substrate for tTGase, we examined in vitro if core histones were subject to cross-linking by tTGase. We found core histone subunits, H2A and H2B, were specifically cross-linked by tTGase. The cross-linking was between either one or both glutamines at C-terminal end of H2A (-VTIAQ104 GGVLPNTQ112 SVLLPKKTESSKSK-C' end) and the first and/or third lysine from C-terminal end of H2B (-AVESEGK116 AVTKYTSSK125-C' end). The cross-linking occurred only when these subunits were released from nucleosome but not when these were organized in nucleosome. Most interestingly, in chicken erythrocyte the cross-linked H2A-H2B was present in a significant amount. From these results, it can be proposed that tTGase-mediated cross-linking is an another form of core histone modification and it may play a role of chromatin condensation during erythrocyte differentiation.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Medicine, Seoul National University, 28 Yongon-Dong, Chongno-Gu, Seoul 110-799, South Korea.
authors.forename: Jae-Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Kang Hoon
authors.initials: KH
authors.lastname: Nam
authors.forename: Oh-Seok
authors.initials: OS
authors.lastname: Kwon
authors.forename: In Gyu
authors.initials: IG
authors.lastname: Kim
authors.forename: Michael
authors.initials: M
authors.lastname: Bustin
authors.forename: Hyon E
authors.initials: HE
authors.lastname: Choy
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Park
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002645:Chickens; D002843:Chromatin / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000378:metabolism; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D012965:Sodium Chloride / Q000494:pharmacology; D011503:Transglutaminases / Q000378:metabolism*
chemical_list: D002843:Chromatin; D003432:Cross-Linking Reagents; D006657:Histones; D009707:Nucleosomes; D010455:Peptides; D012965:Sodium Chloride; D011503:Transglutaminases