Silencing mediator of retinoic

Beside coactivators so-called corepressors exist that are bound to transcription factors such as nuclear receptors and inhibit the initiation of transcription. These factors include the nuclear receptor corepressor (NCoR) and the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT), which interact with nuclear receptors and serve as platforms for complexes containing histone deacetylases (HDACs). These enzymes cause the reversal of histone acetylation of histones leading to a tightening of chromatin and enhancing its inaccessibility for RNA polymerase containing complexes. 

As mentioned earlier, MeCP2 is not the only protein that associates with HD AC activities. Both MBD2 and MBDl repress transcription in histone deacetylation-dependent manner. Interestingly, MBD2 was found associated not only with class I histone deacetylases (HDACl and 2) from the Mi2/NuRD corepressor complex but also with class II histone deacetylases in the silencing mediator of retinoic and thyroid receptor (SMRT)/HDAC 5,7 complex [137]. 

In the absence of ligand, some nuclear hormone receptors associate with co-repressors, namely, SMRT (silencing mediator of retinoic acid and thyroid hormone receptors) and N-CoR (nuclear receptor co-repressor). Both, SMRT and N-CoR, recruit coregulatory protein SINS and histone deacetylases (HDACs) to form a large co-repressor complex that contains histone deacetylase activity, implicating histone deacetylation in transcriptional repression [52,53]. 

Fig. 7. Model for activation by coactivators (A) and inhibition by corepressors (B) of transcription. Abbreviations CBP/p300, cAMP response element binding protein SRC-1, steroid receptor coactivator 1 TBP, TATA-binding protein TAF, TBP-associated factor pol II, RNA polymerase II N-CoR, nuclear receptor corepressor SMRT, silencing mediator of retinoic and thyroid hormone receptors.

Hormone response elements (for steroids, T3, retinoic acid, peptides, etc) act as—or in conjunction with— enhancers or silencers (Chapter 43). Other processes that enhance or silence gene expression—such as the response to heat shock, heavy metals (Cd and Zn +), and some toxic chemicals (eg, dioxin)—are mediated through specific regulatory elements. Tissue-specific expression of genes (eg, the albumin gene in liver, the hemoglobin gene in reticulocytes) is also mediated by specific DNA sequences. 

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