The transcription of the Hairless gene (Hr), which encodes a histone demethylase, is strongly induced by thyroid hormone (T3) in many cell types. This is mediated by heterodimers formed between T3 nuclear receptors and retinoid X receptors. These heterodimers are bound to specific DNA response elements present in regulatory sequences and activate transcription upon T3 binding. To address the significance of this regulation, we identified a single DNA response element upstream of the Hr transcription start site, which plays a key role in this regulation. A single nucleotide mutation in this DNA response element, which prevents the binding of heterodimers, was shown to prevent the activation of Hr by T3 signaling in mice. Analysis of gene expression in the heart and striatum of mice homozygous for this mutation highlights the influence of the Hairless cofactor on thyroid hormone signaling.
Keywords: corepressor/mice; nuclear receptor; thyroid hormone.
© The Author(s) 2026. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com. See the journal About page for additional terms.