Sirtuin 1 Promotes Deacetylation of Oct4 and Maintenance of Naive Pluripotency.
Cell Rep
; 17(3): 809-820, 2016 10 11.
Article
in En
| MEDLINE
| ID: mdl-27732856
ABSTRACT
The enhancer landscape is dramatically restructured as naive preimplantation epiblasts transition to the post-implantation state of primed pluripotency. A key factor in this process is Otx2, which is upregulated during the early stages of this transition and ultimately recruits Oct4 to a different set of enhancers. In this study, we discover that the acetylation status of Oct4 regulates the induction of the primed pluripotency gene network. Maintenance of the naive state requires the NAD-dependent deacetylase, SirT1, which deacetylates Oct4. The activity of SirT1 is reduced during the naive-to-primed transition; Oct4 becomes hyper-acetylated and binds to an Otx2 enhancer to induce Otx2 expression. Induction of Otx2 causes the reorganization of acetylated Oct4 and results in the induction of the primed pluripotency gene network. Regulation of Oct4 by SirT1 may link stem cell development to environmental conditions, and it may provide strategies to manipulate epiblast cell state.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pluripotent Stem Cells
/
Octamer Transcription Factor-3
/
Sirtuin 1
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2016
Type:
Article
Affiliation country:
United States