Novel O-GlcNAcylation on Ser(40) of canonical H2A isoforms specific to viviparity.
We report here newly discovered O-linked-N-acetylglucosamine (O-GlcNAc) modification of histone H2A at Ser(40) (H2AS40Gc). The mouse genome contains 18 H2A isoforms, of which 13 have Ser(40) and the other five have Ala(40). The combination of production of monoclonal antibody and mass spectrometric analyses with reverse-phase (RP)-high performance liquid chromatography (HPLC) fractionation indicated that the O-GlcNAcylation is specific to the Ser(40) isoforms. The H2AS40Gc site is in the L1 loop structure where two H2A molecules interact in the nucleosome. Targets of H2AS40Gc are distributed genome-wide and are dramatically changed during the process of differentiation in mouse trophoblast stem cells. In addition to the mouse, H2AS40Gc was also detected in humans, macaques and cows, whereas non-mammalian species possessing only the Ala(40) isoforms, such as silkworms, zebrafish and Xenopus showed no signal. Genome database surveys revealed that Ser(40) isoforms of H2A emerged in Marsupialia and persisted thereafter in mammals. We propose that the emergence of H2A Ser(40) and its O-GlcNAcylation linked a genetic event to genome-wide epigenetic events that correlate with the evolution of placental animals.
Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, JAPAN.
Mitsuko
M
Hirosawa
Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, JAPAN.
Koji
K
Hayakawa
Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, JAPAN.
Chikako
C
Yoneda
Waseda Research Institute for Science and Engineering, Waseda University Tokyo 169-8555, JAPAN.
Daisuke
D
Arai
Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, JAPAN.
Hitoshi
H
Shiota
Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Saitama 351-0198, JAPAN.
Takehiro
T
Suzuki
Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, JAPAN.
Satoshi
S
Tanaka
Biomolecular Characterization Unit, RIKEN Center for Sustainable Resource Science, Saitama 351-0198, JAPAN.
Naoshi
N
Dohmae
Laboratory of Cellular Biochemistry, Department of Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Tokyo 113-8657, JAPAN.|Waseda Research Institute for Science and Engineering, Waseda University Tokyo 169-8555, JAPAN.
Kunio
K
Shiota
D000117:Acetylglucosamine / Q000737:chemistry*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001665:Binding Sites; D005075:Biological Evolution; D012831:Bombyx; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D053595:Embryonic Stem Cells / Q000166:cytology; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008251:Macaca; D013058:Mass Spectrometry; D051379:Mice; D008810:Mice, Inbred C57BL; D010802:Phylogeny; D020033:Protein Isoforms / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D012694:Serine / Q000737:chemistry; D013045:Species Specificity; D014327:Trophoblasts / Q000378:metabolism; D014981:Xenopus; D015027:Zebrafish
D000911:Antibodies, Monoclonal; D006657:Histones; D020033:Protein Isoforms; D011994:Recombinant Proteins; D012694:Serine; D000117:Acetylglucosamine