| First Author | Yi F | Year | 2011 |
| Journal | Nat Cell Biol | Volume | 13 |
| Issue | 7 | Pages | 762-70 |
| PubMed ID | 21685894 | Mgi Jnum | J:174449 |
| Mgi Id | MGI:5086050 | Doi | 10.1038/ncb2283 |
| Citation | Yi F, et al. (2011) Opposing effects of Tcf3 and Tcf1 control Wnt stimulation of embryonic stem cell self-renewal. Nat Cell Biol 13(7):762-70 |
| abstractText | 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 beta-catenin-binding effectors of Wnt signalling suggested Tcf3-beta-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-beta-catenin and Tcf1-beta-catenin interactions contributed to Wnt stimulation of self-renewal and gene expression, and the combination of Tcf3 and Tcf1 recruited Wnt-stabilized beta-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. |
