First Author | Silberschmidt D | Year | 2011 |
Journal | BMC Dev Biol | Volume | 11 |
Pages | 9 | PubMed ID | 21345181 |
Mgi Jnum | J:169693 | Mgi Id | MGI:4941667 |
Doi | 10.1186/1471-213X-11-9 | Citation | Silberschmidt D, et al. (2011) In vivo role of different domains and of phosphorylation in the transcription factor Nkx2-1. BMC Dev Biol 11:9 |
abstractText | ABSTRACT: BACKGROUND: The transcription factor Nkx2-1 (also known as TTF-1, Titf1 or T/EBP) contains two apparently redundant activation domains and is post-translationally modified by phosphorylation. We have generated mouse mutant strains to assess the roles of the two activation domains and of phosphorylation in mouse development and differentiation. RESULTS: Mouse strains expressing variants of the transcription factor Nkx2-1 deleted of either activation domain have been constructed. Phenotypic analysis shows for each mutant a distinct set of defects demonstrating that distinct portions of the protein endow diverse developmental functions of Nkx2-1. Furthermore, a mouse strain expressing a Nkx2-1 protein mutated in the phosphorylation sites shows a thyroid gland with deranged follicular organization and gene expression profile demonstrating the functional role of phosphorylation in Nkx2-1. CONCLUSIONS: The pleiotropic functions of Nkx2-1 are not all due to the protein as a whole since some of them can be assigned to separate domains of the protein or to specific post-translational modifications. These results have implication for the evolutionary role of mutations in transcription factors. |