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Cited by 70Thyroid Disorders and TreatmentsThyroid Cancer Diagnosis and TreatmentDevelopmental Biology and Gene Regulation

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The Human, but Not Rat, dio2 Gene Is Stimulated by Thyroid Transcription Factor-1 (TTF-1)

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Gereben, Balázs, Salvatore, Domenico, Harney, John W., Tu, Helen M., Larsen, P. Reed·2001·Molecular Endocrinology
DOI 10.1210/mend.15.1.0579
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Abstract

Types 1 and 2 iodothyronine deiodinases (D1 and D2) catalyze the production of T(3) from T(4). D2 mRNA is abundant in the human thyroid but very low in adult rat thyroid, whereas D1 activity is high in both. To understand the molecular regulation of these genes in thyroid cells, the effect of thyroid transcription factor 1 (TTF-1) and the paired domain-containing protein 8 (Pax-8) on the transcriptional activity of the deiodinase promoters were studied. Both the approximately 6.5-kb hdio2 sequence and its most 3' 633 bp were activated 10-fold by transiently expressed TTF-1 in COS-7 cells, but the hdio1 was unaffected. Surprisingly, the response of the rdio2 gene to TTF-1 was only 3-fold despite the 73% identity with the proximal 633-bp region of hdio2 including complete conservation of a functional cAMP response element at -90. Neither human nor rat dio2 nor human dio1 was induced by Pax-8. The binding affinity of four putative TTF-1 binding sites in hdio2 were compared by a semiquantitative gel retardation assay using in vitro expressed TTF-1 homeodomain protein. Only two sites, D and C1 (both of which are absent in rdio2), had significant affinity. Functional analyses showed that both sites are required for the full response to TTF-1. These results can explain the differential expression of dio2 in thyroid and potentially other tissues in humans and rats.

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Metadata

Authors
Gereben, B., Salvatore, D., Harney, J. W., Tu, H. M., & Larsen, P. R.
Affiliations
  • Thyroid Division (B.G., J.W.H., H.M.T., P.R.L.) Department of Medicine Brigham and Women’s Hospital Harvard Medical School Boston, Massachusetts 02115
  • University of Naples Federico II (IT)
  • Brigham and Women's Hospital (US)
Corresponding author
Larsen, P. Reed
ORCID
Salvatore, Domenico
Venue
Molecular Endocrinology
Publisher
The Endocrine Society
Published
2001-01-01
Volume
15
Issue
1
Pages
112-124
ISSN
  • 0888-8809 (ISSN-L)
  • 1944-9917
DOI
10.1210/mend.15.1.0579
OpenAlex
W1979495452
Cited by
70
References
2
Citations by year
2025: 1 · 2024: 3 · 2023: 3 · 2022: 2 · 2021: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 2 · 2015: 2 · 2012: 5
FWCI
4.22
Type
journal article
Language
en
Open access
Locations
  • Molecular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK36256, R01DK036256, T32DK007529)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
TTF-1, PAX8, transcriptional regulation, thyroid-specific gene expression, cAMP response element, thyroid hormone activation
MeSH terms
PAX8 Transcription Factor, Thyroid Nuclear Factor 1, Animals, Base Sequence, Binding Sites, Cell Line, DNA, DNA-Binding Proteins, Humans, Iodide Peroxidase, Iodine Radioisotopes, Kinetics, Male, Molecular Sequence Data, Nuclear Proteins, Promoter Regions, Genetic, Propylthiouracil, RNA, Messenger, Species Specificity, Thyroid Gland, Thyroxine, Transcription Factors, Transcription, Genetic, Trans-Activators, Gene Library, Gene Expression, Rats, Sprague-Dawley, Sequence Homology, Cyclic AMP-Dependent Protein Kinases, Rats, Paired Box Transcription Factors

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