Journal of Hematology & Oncology (Jun 2021)

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

  • Huiqiao Chen,
  • Zixuan Wang,
  • Shanhe Yu,
  • Xiao Han,
  • Yun Deng,
  • Fuhui Wang,
  • Yi Chen,
  • Xiaohui Liu,
  • Jun Zhou,
  • Jun Zhu,
  • Hao Yuan

DOI
https://doi.org/10.1186/s13045-021-01108-z
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 6

Abstract

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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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