| First Author | Luna-Zurita L | Year | 2016 |
| Journal | Cell | Volume | 164 |
| Issue | 5 | Pages | 999-1014 |
| PubMed ID | 26875865 | Mgi Jnum | J:230815 |
| Mgi Id | MGI:5766095 | Doi | 10.1016/j.cell.2016.01.004 |
| Citation | Luna-Zurita L, et al. (2016) Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis. Cell 164(5):999-1014 |
| abstractText | Transcription factors (TFs) are thought to function with partners to achieve specificity and precise quantitative outputs. In the developing heart, heterotypic TF interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5, have been proposed as a mechanism for human congenital heart defects. We report extensive and complex interdependent genomic occupancy of TBX5, NKX2-5, and the zinc finger TF GATA4 coordinately controlling cardiac gene expression, differentiation, and morphogenesis. Interdependent binding serves not only to co-regulate gene expression but also to prevent TFs from distributing to ectopic loci and activate lineage-inappropriate genes. We define preferential motif arrangements for TBX5 and NKX2-5 cooperative binding sites, supported at the atomic level by their co-crystal structure bound to DNA, revealing a direct interaction between the two factors and induced DNA bending. Complex interdependent binding mechanisms reveal tightly regulated TF genomic distribution and define a combinatorial logic for heterotypic TF regulation of differentiation. |
