Thyroid hormone (T3) enters the nucleus and binds thyroid hormone receptor (TR), which is constitutively bound to DNA as a heterodimer with RXR. In the ABSENCE of T3, this complex:

• A Has no effect on transcription until T3 binds
• B Actively represses transcription by recruiting histone deacetylase (HDAC) co-repressor complexes ✓
• C Promotes transcription by recruiting co-activator SRC-1
• D Dissociates from DNA and remains in the cytoplasm bound to chaperones

Explanation

Unliganded TR-RXR heterodimers bound to thyroid hormone response elements (TREs) actively REPRESS target gene transcription by recruiting nuclear co-repressor complexes (NCoR/SMRT) that contain histone deacetylase activity, compacting chromatin. On T3 binding, co-repressors are displaced and co-activators (SRC-1, CBP/p300 with histone acetyltransferase activity) are recruited, activating transcription. This active repression in the unliganded state is the key mechanistic distinction of nuclear receptors from other transcription factors.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.