| 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
|
|
WOS Category
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
CELL BIOLOGY
|
| Resource |
| DNA material |
CSII-EF-MCS-IRES2-Venus (RDB04384)
pCAG-HIVgp (RDB04394)
pCMV-VSV-G-RSV-Rev (RDB04393). |
