RRC ID 39501
Author Nakatani T, Yamagata K, Kimura T, Oda M, Nakashima H, Hori M, Sekita Y, Arakawa T, Nakamura T, Nakano T.
Title Stella preserves maternal chromosome integrity by inhibiting 5hmC-induced γH2AX accumulation.
Journal EMBO Rep
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.
Volume 16(5)
Pages 582-9
Published 2015-5-1
DOI 10.15252/embr.201439427
PII embr.201439427
PMID 25694116
PMC PMC4428038
MeSH 5-Methylcytosine / analogs & derivatives Animals Cell Division Cell Line Cells, Cultured Chromosomal Instability* Chromosomal Proteins, Non-Histone Chromosome Aberrations Chromosome Segregation Cytosine / analogs & derivatives* Cytosine / metabolism DNA Methylation DNA Replication DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Dioxygenases Embryo, Mammalian / cytology Embryo, Mammalian / metabolism Epigenesis, Genetic Female Gene Knockout Techniques Histones / metabolism* Male Mice Protein Transport Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism Repressor Proteins / genetics Repressor Proteins / metabolism* Zygote / metabolism
IF 7.497
Times Cited 22
DNA material CSII-EF-MCS-IRES2-Venus (RDB04384) pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393).