Thyroid hormone (T3) exerts genomic effects by binding to thyroid hormone receptors (TRs). In the absence of T3, unliganded TR bound to thyroid response elements (TREs) on target gene promoters:
- A Has no effect on transcription and dissociates from DNA until T3 is present
- B Actively represses transcription by recruiting histone deacetylase (HDAC)-containing co-repressor complexes ✓
- C Constitutively activates basal transcription independently of T3 binding
- D Promotes methylation of CpG islands in promoter regions, causing irreversible silencing
Explanation
Unliganded TR (particularly TRbeta1) binds TREs and recruits co-repressor complexes including NCoR and SMRT, which associate with histone deacetylases. This creates a transcriptionally repressed chromatin state. On T3 binding, the co-repressor complex is replaced by co-activator complexes (SRC/p160 family) with histone acetyltransferase activity, opening chromatin and activating transcription. This explains why hypothyroidism is not merely reduced T3 action but an actively repressive state — accounting for the disproportionate severity of congenital hypothyroidism.
Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.
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Written and medically reviewed by the StethoPrep medical team.