Pendrin is a novel in vivo downstream target gene of the TTF-1/Nkx-2.1 homeodomain transcription factor in differentiated thyroid cells
Open accessAbstract
Thyroid transcription factor gene 1 (TTF-1) is a homeobox-containing gene involved in thyroid organogenesis. During early thyroid development, the homeobox gene Nkx-2.5 is expressed in thyroid precursor cells coincident with the appearance of TTF-1. The aim of this study was to investigate the molecular mechanisms underlying thyroid-specific gene expression. We show that the Nkx-2.5 C terminus interacts with the TTF-1 homeodomain and, moreover, that the expression of a dominant-negative Nkx-2.5 isoform (N188K) in thyroid cells reduces TTF-1-driven transcription by titrating TTF-1 away from its target DNA. This process reduced the expression of several thyroid-specific genes, including pendrin and thyroglobulin. Similarly, down-regulation of TTF-1 by RNA interference reduced the expression of both genes, whose promoters are sensitive to and directly associate with TTF-1 in the chromatin context. In conclusion, we demonstrate that pendrin and thyroglobulin are downstream targets in vivo of TTF-1, whose action is a prime factor in controlling thyroid differentiation in vivo.
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TTF1 is the main transcriptional activator of the PDS promoter, controlling PDS expression in thyroid cells.
“TTF1 is the main transcriptional activator of the PDS promoter, controlling the expression of PDS in thyroid cells ( Figure 3D ) (171).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [171]
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Thyroid transcription factors in development, differentiation and disease
Fernández, L. P., López-Márquez, A., & Santisteban, P. (2015) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.186 · Cited by 258 · see citing works
Kühnen, P., Turan, S., Fröhler, S., Güran, T., Abali, S., Biebermann, H., Bereket, A., Grüters, A., Chen, W., & Krude, H. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-2619 · Cited by 63 · see citing works
Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion
Jing, L., & Zhang, Q. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.992883 · Cited by 61 · see citing works
- Authors
- Dentice, M., Luongo, C., Elefante, A., Ambrosio, R., Salzano, S., Zannini, M., Nitsch, R., Di Lauro, R., Rossi, G., Fenzi, G., & Salvatore, D.
- Affiliations
- Dipartimento di Biologia e Patologia Cellulare e Molecolare
- University of Naples Federico II (IT)
- Institute for Experimental Endocrinology and Oncology (IT)
- ORCID
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2005-11-01
- Volume
- 25
- Issue
- 22
- Pages
- 10171-10182
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC1280265
- OpenAlex
- W2163916019
- Cited by
- 48
- References
- 0
- Citations by year
- 2026: 3 · 2024: 2 · 2022: 3 · 2021: 2 · 2019: 2 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 3
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministero dell’Istruzione, dell’Università e della Ricerca
- Associazione Italiana per la Ricerca sul Cancro
- 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
- TTF-1, Nkx2.5, pendrin, thyroglobulin, thyroid differentiation, homeodomain transcription factor, dominant-negative isoform, thyroid-specific gene expression, transcriptional regulation, thyroid development, chromatin binding
- MeSH terms
- Thyroid Nuclear Factor 1, Sulfate Transporters, Animals, Base Sequence, Binding Sites, Cell Differentiation, Chromatin, DNA, Gene Expression Regulation, Genes, Dominant, HeLa Cells, Humans, Introns, Ions, Molecular Sequence Data, Nuclear Proteins, Oligonucleotides, Plasmids, Protein Binding, RNA, Messenger, Thyroid Gland, Thyroid Neoplasms, Transcription Factors, Transfection, Blotting, Northern, Blotting, Western, Down-Regulation, Protein Structure, Tertiary, Protein Isoforms, Reverse Transcriptase Polymerase Chain Reaction, Membrane Transport Proteins, Chloride-Bicarbonate Antiporters, RNA Interference, Chromatin Immunoprecipitation, Immunoprecipitation, Rats
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