Zfp296 negatively regulates H3K9 methylation in embryonic development as a component of heterochromatin.
Sci Rep
; 7(1): 12462, 2017 09 29.
Article
de En
| MEDLINE
| ID: mdl-28963472
ABSTRACT
The Cys2/His2-type zinc finger protein Zfp296 has been implicated in stem cell pluripotency and tumor pathogenesis. However, its mechanisms remain elusive. Here, we demonstrated that a Zfp296 deficiency in mice impairs germ-cell development and embryonic growth. Zfp296 was intracellularly localized to heterochromatin in embryos. A GST-Zfp296 pull-down experiment using ES cell nuclear extract followed by LC-MS/MS showed that Zfp296 interacts with component proteins of heterochromatin (such as HP1, Dnmt1, Dnmt3b, and ATRX) and the NuRD complex. We focused on H3K9 methylation as a hallmark of heterochromatin, and found that Zfp296 overexpression in cultured cells reduces the Suv39h1-mediated H3K9 methylation. Consistent with this finding, in Zfp296 -/- mouse embryos, we observed a global increase in H3K9 methylation in a developmental stage-dependent manner, and showed, by ChIP-qPCR, that the H3K9me3 levels at major satellite repeats were elevated in Zfp296 -/- embryos. Our results demonstrate that Zfp296 is a component of heterochromatin that affects embryonic development by negatively regulating H3K9 methylation.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Hétérochromatine
/
Histone
/
Maturation post-traductionnelle des protéines
/
Développement embryonnaire
/
Protéines de liaison à l'ADN
/
Cellules souches embryonnaires de souris
Langue:
En
Journal:
Sci Rep
Année:
2017
Type de document:
Article
Pays d'affiliation:
Japon