Transcriptional Repression: Conserved and Evolved Features

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Transcriptional Repression: Conserved and Evolved Features Sandhya Payankaulam, Li M. Li, David N. Arnosti  Current Biology  Volume 20, Issue 17, Pages R764-R771 (September 2010) DOI: 10.1016/j.cub.2010.06.037 Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 1 Distinct repression mechanisms used by prokaryotic and eukaryotic repressors. (A) A bacterial repressor (R) directly targets the core transcription machinery in the following stages: i) repressor binds to the promoter proximal sites to block the binding of RNA polymerase (Pol); ii) and iii) repressor binds simultaneously to the promoter with RNA polymerase, inhibiting its transition from closed to open complex, or preventing promoter escape; iv) inhibition of RNA polymerase promoter escape can also occur when repressor binds 3′ of the initiation site. (B) Because of the increased genome complexity and presence of chromatin, eukaryotic repressors (R) rely largely on recruitment of corepressors and chromatin modifying enzymes, including HMTs (histone methyltransferases), HDACs (histone deacetylases), KDMs (lysine demethylases) and chromatin remodeling factors with ATPase activity. In some cases these corepressors interact directly with activators (A) or the basal machinery. Current Biology 2010 20, R764-R771DOI: (10.1016/j.cub.2010.06.037) Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 2 Modulation of corepressor activity through posttranslational modification and small molecules. (A) Subcellular localization of corepressors is affected by posttranslational modifications, such as phosphorylation, SUMOylation or acetylation. (B) Posttranslational modifications of corepressors alter a protein–protein interaction surface, either inhibiting or enhancing the recruitment of corepressors. (C) Binding to cellular compounds may impact the corepressor activity: CtBP is suggested to be a more potent corepressor when bound to NADH compared to NAD+, thus allowing it to function as a cellular redox state sensor. Current Biology 2010 20, R764-R771DOI: (10.1016/j.cub.2010.06.037) Copyright © 2010 Elsevier Ltd Terms and Conditions

Figure 3 Possible mechanisms underlying Groucho-mediated context-dependent repression. (A) Groucho adopts alternative conformations when associated with different repressors, and only spreads when recruited by long-range repressors. (B) Groucho is associated with distinct corepressor complexes that are recruited by different repressors; a form that is capable of spreading is recruited by long-range repressors. Current Biology 2010 20, R764-R771DOI: (10.1016/j.cub.2010.06.037) Copyright © 2010 Elsevier Ltd Terms and Conditions