Thyroid hormone (T3) acts via nuclear receptors. Which of the following best describes the mechanism by which unliganded thyroid hormone receptors (apo-TR) differ from liganded receptors (holo-TR)?
- A Apo-TR requires dimerisation with RXR on the TRE, while holo-TR functions as a monomer
- B Apo-TR recruits corepressors (NCoR/SMRT) to actively repress transcription, while holo-TR recruits coactivators to stimulate transcription ✓
- C Apo-TR cannot bind to thyroid response elements (TREs) in DNA; only T3-bound TR binds DNA
- D Apo-TR is retained in the cytoplasm by Hsp90, while holo-TR translocates to the nucleus
Correct answer: B. Apo-TR recruits corepressors (NCoR/SMRT) to actively repress transcription, while holo-TR recruits coactivators to stimulate transcription
Explanation
Unliganded thyroid hormone receptors (apo-TR) are already bound to TREs in the nucleus in a heterodimer with RXR, but recruit corepressors (NCoR, SMRT) that maintain histone deacetylation and transcriptional repression. When T3 binds, corepressors are released and coactivators (SRC-1, p300) are recruited, switching the complex to transcriptional activation. Unlike steroid receptors, TR does not require ligand for nuclear entry or DNA binding. This active repression by apo-TR explains the severe hypothyroidism seen when TR is present without T3.
Reference: Harper's Illustrated Biochemistry, 32nd ed.
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