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Thyroid transcription factor-1 (TTF-1), a member of  the Nkx2 family of homeodomain-containing proteins, is involved in binding to  and in activating the promoters of several important genes in the thyroid,  lungs, and brain, and in regulating expression of these tissue-specific genes.  We investigated potential roles of sheep (Ovis aries) TTF-1 in  regulating cell fate and organ morphogenesis and in controlling puberty and  reproductive capability of females. We amplified and cloned the sheep TTF-1  full-length DNA for the first time, analyzed its functional domains and  regions, predicted molecular structure of its homeodomain and DNA-binding  sites, and examined its expression in pituitary, brain, thyroid gland, ovary,  and hypothalamus. We found that sheep TTF-1 has a high degree of homologous  identity with that of other mammals, and it has several important domains  including domain N, DNA-binding domain, domain C, TN-domain, domain I, and  NK2-SD. The DNA-binding domain of sheep TTF-1 has 10 potential DNA-binding  sites and is a novel mammalian homeodomain that shows considerable sequence  homology with the corresponding rat homeodomain. Several functional regions in  sheep TTF-1 share high sequence identity with rat TTF-1, indicating that these  regions may have the same activity as in the rat. Expression of TTF-1 in  several specific tissues implies that sheep TTF-1 in involved in sheep sexual  development and reproductive capability. These results suggest a role of sheep  TTF-1 in enhancing sheep reproduction performance and we propose it as a candidate  gene for selection.

Molecular characterization and functional analysis of sheep thyroid transcription factor-1