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Cited by 90Thyroid Disorders and TreatmentsGenomics and Chromatin DynamicsEstrogen and related hormone effects

The Promoter of the Human Type I 5′‐Deiodinase Gene — Mapping of the Transcription Start Site and Identification of a DR+4 Thyroid‐Hormone‐Responsive Element

Jakobs, Tatjana C., Schmutzler, Cornelia, Meissner, Jutta, Köhrle, Josef·1997·European Journal of Biochemistry
DOI 10.1111/j.1432-1033.1997.00288.x
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Abstract

The selenoenzyme thyroxine 5′‐deiodinase type I deiodinates the prohormone thyroxine to the active thyroid hormone 3,3′,5‐triiodothyronine. It is thus one of the key enzymes involved in the triiodothyro‐nine‐mediated control of growth, differentiation and basal metabolism in vertebrates. We report here the identification of the transcription start site and the cloning of 1500 bases of the upstream regulatory region of the human 5′‐deiodinase gene. They contain a complex triiodothyronine‐responsive element at nucleotides –696 to –673, consisting of an ideal direct repeat (DR) of two AGGTCA half‐sites with a spacing of four nucleotides (DR+4) and a third putative AGTTCA half‐site with a spacing of another two nucleotides (DR+2). The whole DR+4+2 specifically bound to thyroid hormone receptor and retinoid X receptor in electrophoretic mobility shift assays. The DR+4+2 mediates triiodothyronine‐responsiveness in cotransfection experiments of constructs containing the 5′‐deiodinase upstream promoter and enhancer region fused to luciferase or chloramphenicol acetyltransferase reporter genes with expression plasmids of thyroid hormone receptor subtypes. Also, an about 2.5‐fold induction of the 5′‐deiodinase‐promoter–luciferase‐reporter construct by all‐trans retinoic acid was observed in a cotransfection assay with retinoic acid receptors. Point mutation analysis of the DR+4+2 type hormone‐responsive element, however, revealed that it does not alone mediate the retinoic acid effect. The transcription start point of the 5′‐deiodinase gene was mapped to nucleotides ‐23 and ‐24. No CAAT or TATA box is located within the usual distance to the transcription initiation site. Two GC boxes were found at nucleotides ‐68 to ‐63 and ‐39 to ‐34. Transfection analysis revealed that the proximal 105 nucleotides in the 5′‐flanking region of the 5′‐deiodinase gene act as a functional core promoter. This data indicates that triiodothyronine, the end product of thyroid hormone synthesis, positively regulates one of the key enzymes in its production.

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  • Proinflammatory cytokines can downregulate various components of TH synthesis and metabolism in thyrocytes and hepatocytes.

    “Cellular studies clearly showed that proinflammatory cytokines can downregulate various components of TH synthesis and metabolism in thyrocytes [58] and hepatocytes [59–61].”

    From An update on non-thyroidal illness syndrome (2021) · cites this paper as [61]

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Authors
Jakobs, T. C., Schmutzler, C., Meissner, J., & Köhrle, J.
Affiliations
University of Würzburg (DE)
Corresponding author
Köhrle, Josef
ORCID
Venue
European Journal of Biochemistry
Publisher
Wiley
Published
1997-07
Volume
247
Issue
1
Pages
288-297
ISSN
  • 0014-2956 (ISSN-L)
  • 1432-1033
DOI
10.1111/j.1432-1033.1997.00288.x
OpenAlex
W2015404693
Cited by
90
References
40
Citations by year
2024: 1 · 2023: 1 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 2 · 2012: 8
FWCI
3.80
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 2572 d)
Locations
  • European Journal of Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
thyroxine 5'-deiodinase, transcription start sites, triiodothyronine, thyroid hormone receptor, retinoid X receptor, retinoic acid, core promoter, Sp1 binding site, selenoenzymes, gene expression regulation, promoter mapping, enhancers, luciferase reporter
MeSH terms
Base Sequence, Binding Sites, Cloning, Molecular, Deoxyribonuclease I, Humans, Iodide Peroxidase, Molecular Sequence Data, Promoter Regions, Genetic, Thyroid Hormones, Transcription, Genetic, Transfection, Tretinoin, Tumor Cells, Cultured

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