Format

Send to

Choose Destination
See comment in PubMed Commons below
Sci Rep. 2013 Dec 13;3:3492. doi: 10.1038/srep03492.

Roles for Tbx3 in regulation of two-cell state and telomere elongation in mouse ES cells.

Author information

1
State Key Laboratory of Medicinal Chemical Biology; Department of Cell Biology and Genetics, College of Life Sciences, Nankai University, Tianjin 300071, China.
2
Department of Obstetrics and Gynecology, University of South Florida College of Medicine, Tampa, FL 33612, USA.

Abstract

Mouse embryonic stem (ES) cell cultures exhibit heterogeneity and recently are discovered to sporadically enter the 2-cell (2C)-embryo state, critical for ES potency. Zscan4 could mark the sporadic 2C-state of ES cells. However, factors that regulate the Zscan4(+)/2C state remain to be elucidated. We show that Tbx3 plays a novel role in regulation of Zscan4(+)/2C state. Tbx3 activates 2-cell genes including Zscan4 and Tcstv1/3, but not vise versa. Ectopic expression of Tbx3 results in telomere elongation, consistent with a role for Zscan4 in telomere lengthening. Mechanistically, Tbx3 decreases Dnmt3b and increases Tet2 protein levels, and reduces binding of Dnmt3b to subtelomeres, resulting in reduced DNA methylation and derepression of genes at subtelomeres, e.g. Zscan4. These data suggest that Tbx3 can activate Zscan4(+)/2C state by negative regulation of DNA methylation at repeated sequences, linking to telomere maintenance and self-renewal of ES cells.

PMID:
24336466
PMCID:
PMC3861804
DOI:
10.1038/srep03492
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center