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Fig. 2 | Clinical Diabetes and Endocrinology

Fig. 2

From: A clinician’s guide to understanding resistance to thyroid hormone due to receptor mutations in the TRα and TRβ isoforms

Fig. 2

Role of co-activator and co-repressor recruitment in positively-regulated target genes. a For positively-regulated target genes, in the presence of T3, co-activators (Co-A) and histone acetyl transferases (HAT) are recruited by the T3-bound TR/RXR heterodimer sitting on the thyroid hormone response element (TRE). This leads to histone acetylation and chromatin nearby changes to a more open conformation to facilitate recruitment of RNA pol II to the TATA box region. Subsequently another co-activator complex, TH receptor-associated protein/vitamin D receptor interacting protein complex (TRAP/DRIP comp), is recruited by ligand-bound TR/RXR and RNA polymerase II complex to activate transcription. b For positively-regulated target genes in the absence of T3, TR/RXR has a different conformation than its T3-bound state, and has poor affinity for co-activator complexes. Instead, it recruits a co-repressor complex (Co-R) with histone deacetylase activity (HDAC). This leads to histone deacetylation and formation of a more closed chromatin conformation that does not allow RNA pol II binding to the promoter and thus “represses” transcription. c In some negatively-regulated target genes, in the presence of ligand, co-repressor and HDAC are recruited by TR/RXR sitting on the TRE. This leads to decreased histone acetylation and a more closed chromatin conformation that prevents RNA pol II binding to the promoter of the target gene, and thus negatively regulates transcription in the presence of T3. Please see text for more details

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