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EMBO Rep. 2015 May;16(5):582-9. doi: 10.15252/embr.201439427. Epub 2015 Feb 17.

Stella preserves maternal chromosome integrity by inhibiting 5hmC-induced γH2AX accumulation.

Author information

1
Department of Pathology, Medical School, Osaka University, Osaka, Japan.
2
Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
3
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.
4
Department of Pathology, Medical School, Osaka University, Osaka, Japan Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
5
Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
6
Department of Pathology, Medical School, Osaka University, Osaka, Japan Kitasato University School of Science, Kanagawa, Japan.
7
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.
8
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.

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.

KEYWORDS:

5‐hydroxymethylcytosine; Stella; Tet3; gammaH2AX; zygote

PMID:
25694116
PMCID:
PMC4428038
DOI:
10.15252/embr.201439427
[Indexed for MEDLINE]
Free PMC Article

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