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

The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.

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

Open access
Gereben, Balázs, Salvatore, Domenico, Harney, John W., Tu, Helen M., Larsen, P. Reed·2001·Molecular Endocrinology
DOI 10.1210/mend.15.1.0579
Open this paper in CoChat — free accountOpen PDF

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.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1210/mend.15.1.0579

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 2 references

Research works printed but not linked: 52

  1. Valverde, 1997, Cloning and expression of a 5′-iodothyronine deiodinase from the liver of Fundulus heteroclitus., Endocrinology, 138, 642, 10.1210/endo.138.2.4904 · DOI
  2. Davey, 1995, Cloning of a cDNA for the type II iodothyronine deiodinase., J Biol Chem, 270, 26786, 10.1074/jbc.270.45.26786 · DOI
  3. Gereben, 1999, Cloning and expression of the chicken type 2 iodothyronine 5′-deiodinase., J Biol Chem, 274, 13768, 10.1074/jbc.274.20.13768 · DOI
  4. Croteau, 1996, Cloning of the mammalian type II iodothyronine deiodinase. A selenoprotein differentially expressed and regulated in human and rat brain and other tissues., J Clin Invest, 98, 405, 10.1172/JCI118806 · DOI
  5. Davey, 1999, Cloning of a 5.8 kb cDNA for a mouse type 2 deiodinase., Endocrinology, 140, 1022, 10.1210/endo.140.2.6678 · DOI
  6. Salvatore, 1996, Molecular biological and biochemical characterization of the human type 2 selenodeiodinase., Endocrinology, 137, 3308, 10.1210/endo.137.8.8754756 · DOI · Paper page
  7. Sugawara, 1984, Thyroid T4 5′-deiodinase activity in normal and abnormal human thyroid glands., Metabolism, 33, 332, 10.1016/0026-0495(84)90194-X · DOI
  8. Borges, 1990, Iodothyronine deiodinase activities in FRTL5 cells: predominance of type I 5′-deiodinase., Endocrinology, 126, 3059, 10.1210/endo-126-6-3059 · DOI
  9. Guazzi, 1990, Thyroid nuclear factor 1 (TTF-1) contains a homeodomain and displays a novel DNA binding specificity., EMBO J, 9, 3631, 10.1002/j.1460-2075.1990.tb07574.x · DOI
  10. Lazzaro, 1991, The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain., Development, 113, 1093, 10.1242/dev.113.4.1093 · DOI
  11. Damante, 1994, Thyroid-specific gene expression., Biochim Biophys Acta, 1218, 255, 10.1016/0167-4781(94)90176-7 · DOI
  12. Bohinski, 1994, The lung-specific surfactant protein B gene promoter is a target for thyroid transcription factor 1 and hepatocyte nuclear factor 3, indicating common factors for organ-specific gene expression along the foregut axis., Mol Cell Biol, 14, 5671, 10.1128/MCB.14.9.5671 · DOI
  13. Kimura, 1996, The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary., Genes Dev, 10, 60, 10.1101/gad.10.1.60 · DOI
  14. Plachov, 1990, Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland., Development, 110, 643, 10.1242/dev.110.2.643 · DOI
  15. Zannini, 1992, Pax-8, a paired domain-containing protein, binds to a sequence overlapping the recognition site of a homeodomain and activates transcription from two thyroid- specific promoters., Mol Cell Biol, 12, 4230, 10.1128/MCB.12.9.4230 · DOI · Paper page
  16. Francis-Lang, 1992, Cell type-specific expression of the rat thyroperoxidase promoter indicates common mechanisms for thyroid-specific gene expression., Mol Cell Biol, 12, 576, 10.1128/MCB.12.2.576 · DOI
  17. Zannini, 1997, 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., EMBO J, 16, 3185, 10.1093/emboj/16.11.3185 · DOI · Paper page
  18. Perrone, 2000, The thyroid transcription factor 2 (TTF-2) is a promoter-specific DNA-binding independent transcriptional repressor., Biochem Biophys Res Commun, 275, 203, 10.1006/bbrc.2000.3232 · DOI
  19. Bartha, 2000, Characterization of the 5′-flanking and 5′-untranslated regions of the cyclic adenosine 3′,5′-monophosphate-responsive human type 2 iodothyronine deiodinase gene., Endocrinology, 141, 229, 10.1210/endo.141.1.7282 · DOI · Paper page
  20. Silva, 1983, Adrenergic activation of triiodothyronine production in brown adipose tissue., Nature, 305, 712, 10.1038/305712a0 · DOI
  21. Fabbro, 1995, Definition of the DNA-binding specificity of TTF-1 homeodomain by chromatographic selection of binding sequences., Biochem Biophys Res Commun, 213, 781, 10.1006/bbrc.1995.2198 · DOI
  22. Toyoda, 1995, A novel retinoid X receptor-independent thyroid hormone response element is present in the human type 1 deiodinase gene., Mol Cell Biol, 15, 5100, 10.1128/MCB.15.9.5100 · DOI · Paper page
  23. Prost, 1986, CAT vectors for analysis of eukaryotic promoters and enhancers., Gene, 45, 107, 10.1016/0378-1119(86)90138-1 · DOI
  24. Brent, 1989, Functional characterization of the rat growth hormone promoter elements required for induction by thyroid hormone with and without a co-transfected β type thyroid hormone receptor., J Biol Chem, 264, 178, 10.1016/S0021-9258(17)31240-1 · DOI
  25. Leonard, 1988, Dibutyryl cAMP induction of type II 5′deiodinase activity in rat brain astrocytes in culture., Biochem Biophys Res Commun, 151, 1164, 10.1016/S0006-291X(88)80488-1 · DOI
  26. Missero, 1998, Molecular events involved in differentiation of thyroid follicular cells., Mol Cell Endocrinol, 140, 37, 10.1016/S0303-7207(98)00027-6 · DOI
  27. Bates, 1999, Expression profiles of the three iodothyronine deiodinases, D1, D2, and D3, in the developing rat., Endocrinology, 140, 844, 10.1210/endo.140.2.6537 · DOI
  28. Sinclair, 1990, The tissue-specific expressin of the thyroglobulin gene requires interaction between thyroid-specific and ubiquitous factors., Eur J Biochem, 193, 311, 10.1111/j.1432-1033.1990.tb19339.x · DOI
  29. Endo, 1997, Thyroid transcription factor-1 activates the promoter activity of rat thyroid Na+/I− symporter gene., Mol Endocrinol, 11, 1747
  30. Civitareale, 1993, Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene., Mol Endocrinol, 7, 1589
  31. Kim, 1989, Drosophila NK-homeobox genes., Proc Natl Acad Sci USA, 86, 7716, 10.1073/pnas.86.20.7716 · DOI
  32. Damante, 1991, Several regions of Antennapedia and thyroid transcription factor 1 homeodomains contribute to DNA binding specificity., Proc Natl Acad Sci USA, 88, 5388, 10.1073/pnas.88.12.5388 · DOI
  33. Pick, 1990, Analysis of the ftz upstream element: germ layer-specific enhancers are independently autoregulated., Genes Dev, 4, 1224, 10.1101/gad.4.7.1224 · DOI
  34. Baumruker, 1988, OBP100 binds remarkably degenerate octamer motifs through specific interactions with flanking sequences., Genes Dev, 2, 1400, 10.1101/gad.2.11.1400 · DOI
  35. Christophe-Hobertus, 1999, Two binding sites for thyroid transcription factor 1 (TTF-1) determine the activity of the bovine thyroglobulin gene upstream enhancer element., Mol Cell Endocrinol, 149, 79, 10.1016/S0303-7207(98)00250-0 · DOI
  36. Laughon, 1991, DNA binding specificity of homeodomains., Biochemistry, 30, 11357, 10.1021/bi00112a001 · DOI
  37. Civitareale, 1989, A thyroid-specific nuclear protein essential for tissue- specific expression of the thyroglobulin promoter., EMBO J, 8, 2537, 10.1002/j.1460-2075.1989.tb08391.x · DOI
  38. Song, 2000, Isolation and characterization of the 5′-upstream and untranslated regions of the mouse type II iodothyronine deiodinase gene., Mol Cell Endocrinol, 165, 189, 10.1016/S0303-7207(00)00246-X · DOI
  39. Steinsapir, 1998, Type 2 iodothyronine deiodinase in rat pituitary tumor cells is inactivated in proteasomes., J Clin Invest, 102, 1895, 10.1172/JCI4672 · DOI · Paper page
  40. Steinsapir, 2000, Substrate-induced down-regulation of human type 2 deiodinase (hD2) is mediated through proteasomal degradation and requires interaction with the enzyme’s active center., Endocrinology, 141, 1127, 10.1210/endo.141.3.7355 · DOI · Paper page
  41. Ordonez, 2000, Thyroid transcription factor-1 is a marker of lung and thyroid carcinomas., Adv Anat Pathol, 7, 123, 10.1097/00125480-200007020-00007 · DOI
  42. Venkataraman, 1999, Restoration of iodide uptake in dedifferentiated thyroid carcinoma: relationship to human Na+/I-symporter gene methylation status., J Clin Endocrinol Metab, 84, 2449
  43. Brunetti, 2000, The 3′,5′-cyclic adenosine monophosphate response element binding protein (CREB) is functionally reduced in human toxic thyroid adenomas., Endocrinology, 141, 722, 10.1210/endo.141.2.7331 · DOI
  44. Campos-Barros, 1996, Phenolic and tyrosyl ring iodothyronine deiodination and thyroid hormone concentrations in the human central nervous system., J Clin Endocrinol Metab, 81, 2179
  45. Salvatore, 1998, The guanosine monophosphate reductase gene is conserved in rats and its expression increases rapidly in brown adipose tissue during cold exposure., J Biol Chem, 273, 31092, 10.1074/jbc.273.47.31092 · DOI
  46. Kadobayashi, 1999, Effect of 12-O-tetradecanoylphorbol 13- acetate on type 2 iodothyronine deiodinase in cultured human thyroid cells., Program of the 72nd Annual Meeting of the American Thyroid Association, 43
  47. Maurer, 1989, Both isoforms of the cAMP-dependent protein kinase catalytic subunit can activate transcription of the prolactin gene., J Biol Chem, 264, 6870, 10.1016/S0021-9258(18)83511-6 · DOI
  48. Seed, 1988, A simple phase-extraction assay for chloramphenicol acetyltransferase activity., Gene, 67, 271, 10.1016/0378-1119(88)90403-9 · DOI
  49. Selden, 1986, Human growth hormone as a reporter gene in regulation studies employing transient gene expression., Mol Cell Biol, 6, 3173, 10.1128/MCB.6.9.3173 · DOI
  50. Chomczynski, 1995, Single-step isolation of RNA from cultured cells or tissues., Current Protocols in Molecular Biology., 4.2.4
  51. Lehrach, 1977, RNA molecular weight determinations by gel electrophoresis under denaturing conditions, a critical reexamination., Biochemistry, 16, 4743, 10.1021/bi00640a033 · DOI
  52. Berry, 1990, Thyroid hormone regulates type I deiodinase messenger RNA in rat liver., Mol Endocrinol, 4, 743, 10.1210/mend-4-5-743 · DOI

Cited by

Sorted by citations

See all 70

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: The Human, but Not Rat, dio2 Gene Is Stimulated by Thyroid Transcription Factor-1 (TTF-1). https://app.cochat.ai/papers/10.1210/mend.15.1.0579
The paper
Gereben, B., Salvatore, D., Harney, J. W., Tu, H. M., & Larsen, P. R. (2001). The Human, but Not Rat, dio2 Gene Is Stimulated by Thyroid Transcription Factor-1 (TTF-1). Molecular Endocrinology. https://doi.org/10.1210/mend.15.1.0579