3,3',5-Triiodothyroacetic acid (TRIAC) induces embryonic ζ-globin expression via thyroid hormone receptor α.

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  • Additional Information
    • Source:
      Publisher: Biomed Central Country of Publication: England NLM ID: 101468937 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-8722 (Electronic) Linking ISSN: 17568722 NLM ISO Abbreviation: J Hematol Oncol Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Biomed Central, 2008-
    • Subject Terms:
      Gene Expression/*drug effects ; Thyroid Hormone Receptors alpha/*genetics ; Triiodothyronine/*analogs & derivatives ; Up-Regulation/*drug effects ; zeta-Globins/*genetics; Animals ; Gene Expression Regulation, Developmental/drug effects ; Humans ; K562 Cells ; Thyroid Hormone Receptors alpha/deficiency ; Triiodothyronine/pharmacology ; Zebrafish/embryology ; Zebrafish/genetics ; Zebrafish Proteins/genetics
    • Abstract:
      The human ζ-globin gene (HBZ) is transcribed in primitive erythroid cells only during the embryonic stages of development. Reactivation of this embryonic globin synthesis would likely alleviate symptoms both in α-thalassemia and sickle-cell disease. However, the molecular mechanisms controlling ζ-globin expression have remained largely undefined. Moreover, the pharmacologic agent capable of inducing ζ-globin production is currently unavailable. Here, we show that TRIAC, a bioactive thyroid hormone metabolite, significantly induced ζ-globin gene expression during zebrafish embryogenesis. The induction of ζ-globin expression by TRIAC was also observed in human K562 erythroleukemia cell line and primary erythroid cells. Thyroid hormone receptor α (THRA) deficiency abolished the ζ-globin-inducing effect of TRIAC. Furthermore, THRA could directly bind to the distal enhancer regulatory element to regulate ζ-globin expression. Our study provides the first evidence that TRIAC acts as a potent inducer of ζ-globin expression, which might serve as a new potential therapeutic option for patients with severe α-thalassemia or sickle-cell disease.
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    • Contributed Indexing:
      Keywords: Sickle-cell disease; Thalassemia; Thyroid hormone; ζ-Globin
    • Accession Number:
      0 (Thyroid Hormone Receptors alpha)
      0 (Zebrafish Proteins)
      0 (zeta-Globins)
      06LU7C9H1V (Triiodothyronine)
      29OQ9EU4R1 (3,3',5-triiodothyroacetic acid)
    • Publication Date:
      Date Created: 20210627 Date Completed: 20211101 Latest Revision: 20211101
    • Publication Date:
      20231215
    • Accession Number:
      PMC8235803
    • Accession Number:
      10.1186/s13045-021-01108-z
    • Accession Number:
      34174920