title: Stella preserves maternal chromosome integrity by inhibiting 5hmC-induced γH2AX accumulation.
abstract: In the mouse zygote, Stella/PGC7 protects 5-methylcytosine (5mC) of the maternal genome from Tet3-mediated oxidation to 5-hydroxymethylcytosine (5hmC). Although ablation of Stella causes early embryonic lethality, the underlying molecular mechanisms remain unknown. In this study, we report impaired DNA replication and abnormal chromosome segregation (ACS) of maternal chromosomes in Stella-null embryos. In addition, phosphorylation of H2AX (γH2AX), which has been reported to inhibit DNA replication, accumulates in the maternal chromatin of Stella-null zygotes in a Tet3-dependent manner. Cell culture assays verified that ectopic appearance of 5hmC induces abnormal accumulation of γH2AX and subsequent growth retardation. Thus, Stella protects maternal chromosomes from aberrant epigenetic modifications to ensure early embryogenesis.
authors.affiliation: Department of Pathology, Medical School, Osaka University, Osaka, Japan.
authors.forename: Tsunetoshi
authors.initials: T
authors.lastname: Nakatani
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamagata
authors.affiliation: Department of Pathology, Medical School, Osaka University, Osaka, Japan Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan Kitasato University School of Science, Kanagawa, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Kimura
authors.affiliation: Department of Pathology, Medical School, Osaka University, Osaka, Japan Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oda
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakashima
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
authors.forename: Mayuko
authors.initials: M
authors.lastname: Hori
authors.affiliation: Department of Pathology, Medical School, Osaka University, Osaka, Japan Kitasato University School of Science, Kanagawa, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Sekita
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Arakawa
authors.affiliation: Nagahama Institute of Bio-Science and Technology, Shiga, Japan Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan.
authors.forename: Toshinobu
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Pathology, Medical School, Osaka University, Osaka, Japan Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan Core Research for Evolutional Science and Technology (CREST), Japan Science and Technology Agency (JST), Tokyo, Japan tnakano@patho.med.osaka-u.ac.jp.
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D043171:Chromosomal Instability; D002868:Chromosomal Proteins, Non-Histone; D002869:Chromosome Aberrations; D020090:Chromosome Segregation; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019175:DNA Methylation; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D049308:Dioxygenases; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D055786:Gene Knockout Techniques; D006657:Histones / Q000378:metabolism*; D008297:Male; D051379:Mice; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015053:Zygote / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C462180:Dppa3 protein, mouse; D006657:Histones; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D049308:Dioxygenases; C551915:Tet3 protein, mouse
keywords: 5‐hydroxymethylcytosine; Stella; Tet3; gammaH2AX; zygote