| First Author | Elliott KH | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 33006313 | Mgi Jnum | J:296137 |
| Mgi Id | MGI:6467733 | Doi | 10.7554/eLife.56450 |
| Citation | Elliott KH, et al. (2020) Gli3 utilizes Hand2 to synergistically regulate tissue-specific transcriptional networks. Elife 9:e56450 |
| abstractText | Despite a common understanding that Gli TFs are utilized to convey a Hh morphogen gradient, genetic analyses suggest craniofacial development does not completely fit this paradigm. Using the mouse model (Mus musculus), we demonstrated that rather than being driven by a Hh threshold, robust Gli3 transcriptional activity during skeletal and glossal development required interaction with the basic helix-loop-helix TF Hand2. Not only did genetic and expression data support a co-factorial relationship, but genomic analysis revealed that Gli3 and Hand2 were enriched at regulatory elements for genes essential for mandibular patterning and development. Interestingly, motif analysis at sites co-occupied by Gli3 and Hand2 uncovered mandibular-specific, low-affinity, 'divergent' Gli-binding motifs (dGBMs). Functional validation revealed these dGBMs conveyed synergistic activation of Gli targets essential for mandibular patterning and development. In summary, this work elucidates a novel, sequence-dependent mechanism for Gli transcriptional activity within the craniofacial complex that is independent of a graded Hh signal. |
