In vertebrates, the active form of thyroid hormone (T3) acts directly on transcription by changing the conformation of the TR nuclear receptors (TR alpha 1, TR beta 1 et TR beta 2) which are encoded by the THRA and THRB genes. These receptors are bound to DNA at specific response elements in a ligand independent manner. Mouse genetics have clarified the respective function of each receptor isoform, mainly reflecting THRA and THRB expression patterns. It also revealed the importance of negative regulation by unliganded receptors not only in pathological but also in physiological situations.
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