Thyroid-specific enhancer-binding protein (T/EBP) is a homeodomain- containing DNA-binding protein which controls expression of thyroid- and lung-specific genes such as those encoding thyroid peroxidase, thyroglobulin, and the thyroid stimulating hormone (TSH) receptor, and surfactant proteins A, B, and C, and clara cell secretory protein, respectively. A role for T/EBP in mammalian development has been suggested after T/EBP was found to be expressed in rat embryos. Our earlier work on targeted disruption of the mouse T/ebp gene has conclusively demonstrated that T/EBP is essential for organogenesis of the thyroid, lung, ventral forebrain, and pituitary. In order to understand how T/EBP gene expression is controlled and which of its target genes are involved in embryogenesis and in maintenance of the differentiated function of the thyroid and lung, we characterized the upstream sequence of the rat and human T/EBP genes by using cDNA and genomic clonings, northern blotting, and transfection assays. The T/EBP gene possesses a novel structure in the 5'non-coding region that results from differential transcription initiation and splicing. The T/EBP cDNAs can be grouped into 6 different types; four contain an intron of different length whereas the other two contain no intron. Longer T/EBP mRNAs are more abundant in rat FRTL-5 cells maintained in the absence of TSH as compared to its presence, suggesting a correlation between premature mRNA utilization and the physiological state of the cells where T/EBP is expressed. The T/EBP gene expression was further found to be auto-regulated. Detailed analyses of mechanisms controlling T/EBP gene expression are currently under study.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC005522-10
Application #
6160914
Study Section
Special Emphasis Panel (LM)
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
1997
Total Cost
Indirect Cost
Name
National Cancer Institute Division of Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Hoshi, Sayuri; Hoshi, Nobuo; Okamoto, Minoru et al. (2009) Role of NKX2-1 in N-bis(2-hydroxypropyl)-nitrosamine-induced thyroid adenoma in mice. Carcinogenesis 30:1614-9
Hoshi, Nobuo; Kusakabe, Takashi; Taylor, Barbara J et al. (2007) Side population cells in the mouse thyroid exhibit stem/progenitor cell-like characteristics. Endocrinology 148:4251-8
Zhang, Yuzhen; Rath, Nibedita; Hannenhalli, Sridhar et al. (2007) GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo. Development 134:189-98
Yeager, Nicole; Klein-Szanto, Andres; Kimura, Shioko et al. (2007) Pten loss in the mouse thyroid causes goiter and follicular adenomas: insights into thyroid function and Cowden disease pathogenesis. Cancer Res 67:959-66
Yin, Zhan; Gonzales, Linda; Kolla, Venkatadri et al. (2006) Hop functions downstream of Nkx2.1 and GATA6 to mediate HDAC-dependent negative regulation of pulmonary gene expression. Am J Physiol Lung Cell Mol Physiol 291:L191-9
Kusakabe, Takashi; Hoshi, Nobuo; Kimura, Shioko (2006) Origin of the ultimobranchial body cyst: T/ebp/Nkx2.1 expression is required for development and fusion of the ultimobranchial body to the thyroid. Dev Dyn 235:1300-9
Niimi, Tomoaki; Kurotani, Reiko; Kimura, Shioko et al. (2006) Identification and expression of alternative splice variants of the mouse Ppp1r3b gene in lung epithelial cells. Biochem Biophys Res Commun 349:588-96
Kusakabe, Takashi; Kawaguchi, Akio; Hoshi, Nobuo et al. (2006) Thyroid-specific enhancer-binding protein/NKX2.1 is required for the maintenance of ordered architecture and function of the differentiated thyroid. Mol Endocrinol 20:1796-809
Amendola, Elena; De Luca, Pasquale; Macchia, Paolo Emidio et al. (2005) A mouse model demonstrates a multigenic origin of congenital hypothyroidism. Endocrinology 146:5038-47
Shima, Yuichi; Zubair, Mohamad; Ishihara, Satoru et al. (2005) Ventromedial hypothalamic nucleus-specific enhancer of Ad4BP/SF-1 gene. Mol Endocrinol 19:2812-23

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