A SINGLE NUCLEOTIDE DELETION DISRUPTS THE TRANSCRIPTIONAL RESPONSE OF THE HAIRLESS GENE TO THYROID HORMONE AND THYROID HORMONE SIGNALLING IN MICE.

The transcription of the Hairless gene, which encodes a histone demethylase, is strongly induced by thyroid hormone in many cell types. To address the significance of this regulation, we identified a DNA response element in the regulatory sequences of the Hairless gene, which plays a key role in this regulation. A single mutation in this response element proves to be sufficient to alter thyroid hormone signaling in mice. RNA-seq analysis in the heart and striatum of mice homozygous for this mutation highlights the influence of the Hairless cofactor in thyroid hormone signaling. Overall design: RNA-seq analysis was performed on 3 groups of mutant mice (HrDR5/DR5 genotype) and 3 groups of wild-type mice, for two tissues: heart and striatum. The 3 groups correspond to 3 conditions: euthyroid/hypothyroid/hypothyroid treated with thyroid hormone (24h) to quickly restore hormonal levels.