TTF-2, a new forkhead protein, shows a temporal expression in the developing thyroid which is consistent with a role in controlling the onset of differentiation
Open accessAbstract
Expression of thyroglobulin (Tg) and thyroperoxidase (TPO) genes in thyroid follicular cells occurs in the mouse at embryonic day (E)14.5. Two transcription factors, TTF-1 and Pax-8, have been implicated in transcriptional activation of Tg and TPO, even though the onset of their expression is at E9.5, suggesting that additional events are necessary for transcriptional activation of Tg and TPO genes. We report in this paper the cloning of TTF-2, a DNA binding protein that recognizes sites on both Tg and TPO promoters. TTF-2 is a new forkhead domain-containing protein whose expression is restricted to the endodermal lining of the foregut and to the ectoderm that will give rise to the anterior pituitary. TTF-2 shows transient expression in the developing thyroid and anterior pituitary. In the thyroid, TTF-2 expression is down-regulated just before the onset of Tg and TPO gene expression, suggesting that this transcription factor plays the role in development of a negative controller of thyroid-specific gene expression.
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TTF2 interferes with the binding of TTF1 to the TG promoter, inhibiting its transcriptional activation.
“TTF2 could interfere with the binding of TTF1 to the TG promoter, inhibiting its transcriptional activation (167).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [167]
The discussion reports that TTF-2 interferes with TTF-1-mediated transcriptional activation of the Tg promoter, supporting the inhibition part of the claim. It does not establish that TTF-2 interferes with TTF-1 binding to that promoter; the same passage says repression persists when TTF-2 binding sites are mutated. The indexed copy gives no page number for this passage. (LLM, conf=0.86)
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Research works printed but not linked: 4
- Ericson,L.E. and Frederiksson,G. (1990) Phylogeny and ontogeny of the forkhead/HNF-3 α, β, and γ genes in determination of the definitive endoderm, chordamesoderm and neurectoderm. Development, 119, thyroid gland. In Greer,M.A. (ed.), The Thyroid Gland, Comprehensive Endocrinology. Raven Press, New York, NY, pp. 1-35. 567-578.
- Kaestner,K.H., Lee,K.-H., Schlondorff,J., Hiemisch,H., Monaghan,A.P. Strubin,M., Newell,J.W. and Matthias,P. (1995) OBF-1, a novel B-cell- specific coactivator that stimulates immunoglobulin promoter activity and Schutz,G. (1993) Six members of the mouse forkhead gene family are developmentally regulated. Proc. Natl Acad. Sci. USA, 90, through association with octamer-binding proteins. Cell, 80, 497-506.
- Lazzaro,D., Price,M., De Felice,M. and Di Lauro,R. (1991) The transcription factor TTF-1 is expressed at the onset of thyroid and University Press, Oxford, pp. 155-171.
- Luo,Y., Fujii,H., Gerster,T. and Roeder,R.G. (1992) A novel B cell- Sizonenko,P.C., Aubert,M.L. and Vessalli,J.D. (eds), Frontiers in Endocrinology, Vol. 6, Transcription Factors and Differentiation of derived coactivator potentiates the activation of immunoglobulin promoters by octamer-binding transcription factors. Cell, 71, 231-241. Thyroid Follicular Cells. Ares Serono Symposia Publications, Rome, pp. 79-87.
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- Authors
- Zannini, M., Avantaggiato, V., Biffali, E., Arnone, M. I., Sato, K., Pischetola, M., Taylor, B. A., Phillips, S. J., Simeone, A., & Di Lauro, R.
- Affiliations
- Stazione Zoologica Anton Dohrn (IT)
- Institute of Genetics and Biophysics (IT)
- Jackson Laboratory (US)
- Venue
- The EMBO Journal
- Published
- 1997-06-01
- Volume
- 16
- Issue
- 11
- Pages
- 3185-3197
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1169936
- OpenAlex
- W2105168909
- Cited by
- 259
- References
- 0
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 5 · 2023: 6 · 2022: 7 · 2021: 4 · 2020: 4 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 8 · 2015: 8 · 2014: 12 · 2013: 12 · 2012: 6
- FWCI
- 10.56
- Type
- journal article
- Language
- en
- Update notices
- erratum (2001-04-17)
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- Consiglio Nazionale delle Ricerche
- Associazione Italiana per la Ricerca sul Cancro
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM018684, GM 18684)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- forkhead transcription factor, thyroid development, thyroglobulin, thyroid peroxidase, thyroid differentiation, anterior pituitary, endoderm, transcriptional regulation, gene expression timing, promoter binding sites, mouse embryo
- MeSH terms
- PAX8 Transcription Factor, Thyroid Nuclear Factor 1, Amino Acid Sequence, Animals, Base Sequence, Cell Differentiation, Cells, Cultured, Chromosome Mapping, Cloning, Molecular, DNA-Binding Proteins, Insulin, Insulin-Like Growth Factor I, Molecular Sequence Data, Nuclear Proteins, Peroxidases, Pituitary Gland, Anterior, Protein Binding, Repressor Proteins, Thyroglobulin, Thyroid Gland, Time Factors, Transcription Factors, Trans-Activators, Sequence Homology, Amino Acid, Sequence Analysis, DNA, DNA, Complementary, Gene Expression Regulation, Developmental, Mice, Paired Box Transcription Factors, Forkhead Transcription Factors
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