| First Author | Kennedy MW | Year | 2016 |
| Journal | Proc Natl Acad Sci U S A | Volume | 113 |
| Issue | 13 | Pages | 3545-50 |
| PubMed ID | 26969725 | Mgi Jnum | J:232050 |
| Mgi Id | MGI:5775850 | Doi | 10.1073/pnas.1519994113 |
| Citation | Kennedy MW, et al. (2016) Sp5 and Sp8 recruit beta-catenin and Tcf1-Lef1 to select enhancers to activate Wnt target gene transcription. Proc Natl Acad Sci U S A 113(13):3545-50 |
| abstractText | The ancient, highly conserved, Wnt signaling pathway regulates cell fate in all metazoans. We have previously shown that combined null mutations of the specificity protein (Sp) 1/Klf-like zinc-finger transcription factorsSp5andSp8(i.e.,Sp5/8) result in an embryonic phenotype identical to that observed when core components of the Wnt/beta-catenin pathway are mutated; however, their role in Wnt signal transduction is unknown. Here, we show in mouse embryos and differentiating embryonic stem cells that Sp5/8 are gene-specific transcriptional coactivators in the Wnt/beta-catenin pathway. Sp5/8 bind directly to GC boxes in Wnt target gene enhancers and to adjacent, or distally positioned, chromatin-bound T-cell factor (Tcf) 1/lymphoid enhancer factor (Lef) 1 to facilitate recruitment of beta-catenin to target gene enhancers. BecauseSp5is itself directly activated by Wnt signals, we propose that Sp5 is a Wnt/beta-catenin pathway-specific transcripton factor that functions in a feed-forward loop to robustly activate select Wnt target genes. |
