• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal.

The co-occupancy of Tcf3 with Oct4, Sox2 and Nanog on embryonic stem cell (ESC) chromatin indicated that Tcf3 has been suggested to play an integral role in a poorly understood mechanism underlying Wnt-dependent stimulation of mouse ESC self-renewal of mouse ESCs. Although the conventional view of Tcf proteins as the β-catenin-binding effectors of Wnt signalling suggested Tcf3-β-catenin activation of target genes would stimulate self-renewal, here we show that an antagonistic relationship between Wnt3a and Tcf3 on gene expression regulates ESC self-renewal. Genetic ablation of Tcf3 replaced the requirement for exogenous Wnt3a or GSK3 inhibition for ESC self-renewal, demonstrating that inhibition of Tcf3 repressor is the necessary downstream effect of Wnt signalling. Interestingly, both Tcf3-β-catenin and Tcf1-β-catenin interactions contributed to Wnt stimulation of self-renewal and gene expression, and the combination of Tcf3 and Tcf1 recruited Wnt-stabilized β-catenin to Oct4 binding sites on ESC chromatin. This work elucidates the molecular link between the effects of Wnt and the regulation of the Oct4/Sox2/Nanog network.

Pubmed ID: 21685894

Authors

  • Yi F
  • Pereira L
  • Hoffman JA
  • Shy BR
  • Yuen CM
  • Liu DR
  • Merrill BJ

Journal

Nature cell biology

Publication Data

July 4, 2011

Associated Grants

  • Agency: NCI NIH HHS, Id: R01 CA128571
  • Agency: NIGMS NIH HHS, Id: R01 GM065400
  • Agency: NIGMS NIH HHS, Id: R01 GM065400-01
  • Agency: NIGMS NIH HHS, Id: R01 GM065400-02
  • Agency: NIGMS NIH HHS, Id: R01 GM065400-03
  • Agency: NIGMS NIH HHS, Id: R01 GM065400-04
  • Agency: NIGMS NIH HHS, Id: R01 GM065400-05
  • Agency: NIGMS NIH HHS, Id: R01 GM065400-06
  • Agency: NIGMS NIH HHS, Id: R01 GM065400-07
  • Agency: NIGMS NIH HHS, Id: R01 GM065400-08
  • Agency: NIGMS NIH HHS, Id: R01 GM065400-09
  • Agency: NCI NIH HHS, Id: R01-CA128571
  • Agency: NIGMS NIH HHS, Id: R01-GM065400
  • Agency: Howard Hughes Medical Institute, Id:
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Line
  • Cell Proliferation
  • Embryonic Stem Cells
  • Gene Expression Regulation, Developmental
  • Glycogen Synthase Kinase 3
  • Hepatocyte Nuclear Factor 1-alpha
  • Homeodomain Proteins
  • Mice
  • Octamer Transcription Factor-3
  • Protein Kinase Inhibitors
  • RNA Interference
  • SOXB1 Transcription Factors
  • Signal Transduction
  • Transcription, Genetic
  • Transfection
  • Wnt Proteins
  • Wnt3 Protein
  • Wnt3A Protein
  • beta Catenin