Molecular characterization and functional analysis of  sheep thyroid transcription factor-1.
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.
College of Animal Science and Technology, Gansu Agricultural University, Lanzhou, China. zhangliping@gsau.edu.cn
L P
LP
Zhang
B Y
BY
Ma
F X
FX
Han
H L
HL
Wan
J P
JP
Wu
L H
LH
Yu
X R
XR
Wang
J Y
JY
Zhu
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome / Q000235:genetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D051381:Rats; D016415:Sequence Alignment; D012756:Sheep / Q000235:genetics*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D004247:DNA