The highly and perpetually upregulated thyroglobulin gene is a hallmark of functional thyrocytes

Front Cell Dev Biol. 2023 Oct 4:11:1265407. doi: 10.3389/fcell.2023.1265407. eCollection 2023.

Abstract

Abnormalities are indispensable for studying normal biological processes and mechanisms. In the present work, we draw attention to the remarkable phenomenon of a perpetually and robustly upregulated gene, the thyroglobulin gene (Tg). The gene is expressed in the thyroid gland and, as it has been recently demonstrated, forms so-called transcription loops, easily observable by light microscopy. Using this feature, we show that Tg is expressed at a high level from the moment a thyroid cell acquires its identity and both alleles remain highly active over the entire life of the cell, i.e., for months or years depending on the species. We demonstrate that this high upregulation is characteristic of thyroglobulin genes in all major vertebrate groups. We provide evidence that Tg is not influenced by the thyroid hormone status, does not oscillate round the clock and is expressed during both the exocrine and endocrine phases of thyrocyte activity. We conclude that the thyroglobulin gene represents a unique and valuable model to study the maintenance of a high transcriptional upregulation.

Keywords: gene upregulation; thyroglobulin gene; thyroid hormones; transcription; transcription loop.

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This work has been supported by the Deutsche Forschungsgemeinschaft grants (SP2202/SO1054/2, project # 422388934 to IS, SPP 2202/LE721/17-1, project # 422857584 to HL, and SFB1064, project # 213249687 to HL and IS; SPP 1629/HE3418/7-2 to HH); The Belgian National Fund for Scientific Research (FNRS) (PDR T.0140.14; PDR T.0230.18, CDR J.0068.22), the Fonds d’Encouragement à la Recherche de l’Université Libre de Bruxelles (FER-ULB) and the European Union’s Horizon 2020 research and innovation program under grant agreement No. 825745 (to SC); The French National Research center (CNRS) and the Muséum National of Natural History (to J-BF.)