| First Author | Guo Q | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 33587034 | Mgi Jnum | J:357126 |
| Mgi Id | MGI:6806498 | Doi | 10.7554/eLife.64444 |
| Citation | Guo Q, et al. (2021) A beta-catenin-driven switch in TCF/LEF transcription factor binding to DNA target sites promotes commitment of mammalian nephron progenitor cells. Elife 10 |
| abstractText | The canonical Wnt pathway transcriptional co-activator beta-catenin regulates self-renewal and differentiation of mammalian nephron progenitor cells (NPCs). We modulated beta-catenin levels in NPC cultures using the GSK3 inhibitor CHIR99021 (CHIR) to examine opposing developmental actions of beta-catenin. Low CHIR-mediated maintenance and expansion of NPCs are independent of direct engagement of TCF/LEF/beta-catenin transcriptional complexes at low CHIR-dependent cell-cycle targets. In contrast, in high CHIR, TCF7/LEF1/beta-catenin complexes replaced TCF7L1/TCF7L2 binding on enhancers of differentiation-promoting target genes. Chromosome confirmation studies showed pre-established promoter-enhancer connections to these target genes in NPCs. High CHIR-associated de novo looping was observed in positive transcriptional feedback regulation to the canonical Wnt pathway. Thus, beta-catenin's direct transcriptional role is restricted to the induction of NPCs, where rising beta-catenin levels switch inhibitory TCF7L1/TCF7L2 complexes to activating LEF1/TCF7 complexes at primed gene targets poised for rapid initiation of a nephrogenic program. |
