25 - Transcription (Eukaryotes); Molecular Mechanisms

25 - Transcription (Eukaryotes); Molecular Mechanisms -...

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Sin city November 19 th Federation Hall Tickets: $10 + non perishable food item $12 without Available at SciSoc (Phys 345) & Science CnD All faculties welcome Non uw 19+ Bring id and watcard ARE YOU FEELING LUCKY? SCIBALL 2011
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Co-activators (co-repressors) and Mediator Complex Co-activators (co-repressors) : direct contact with activators or repressors (through transcription activation domain) Have specific role, for example involvement in histone modifications nuclear receptors Int J Biol Sci 2006; 2:38-47
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•DNA is tightly packed in nucleosomes: is not easy for RNAP II to bind to the promoter – cooperation of different proteins is needed – help and extra control •Proteins in Mediator Complexes are evolutionary conserved Bridging through Mediator Complex – protein complex necessary for the assembly of the preinitiation complex (PIC) in some of the genes ; (communicates directly with gene-specific TFs and GTFs) Why Mediator Complexes? •Activator domains contact different mediator components – fine tuning
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Model for mediator function A particular combinations of activators assembled on a particular combination of promoter elements is responsible for the particular conformation of the mediator complex A conformation of the mediator complex could influence the pace of the RNAP II re-entry (next round of initiation) TWO PROMOTERS: A and B A: mediator conformation for the slow re- entry of RNAPII (activators A and B bound to the respective cis elements) B: for the faster RNAPII re-entry (activators A, X and Y bound to the respective cis elements) Lewis, B. A. et al. J Cell Sci 2003;116:3667-3675
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Roeder, R.G. (2005) Transcriptional regulation and the role of diverse coactivators in animal cells. FEBS Lett, 579, 909-915.
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How is transcription initiation influenced (different molecular mechanisms) 1. Direct influence of TFs on assembly of initiation complexes (review): interactions of TFs with modulator complex, co-activators (or co-repressors), each other, ligands promote or prevent recruitment and binding of GTFs TFs form enhancesomes (action from the distance on binding of GTFs) TFs cause architectural changes in DNA in order to promote binding of other GTFs Presence and role of insulators 2. TFs regulate changes in chromatin structure (remodeling) and control histone acetylation and deacetylation (review) 3. Concentration and activities of TFs are regulated during cell differentiation and/or in response to hormones and signals from other cells – cell signaling 4. Protection of active gene promoters from methylation (and methylation of promoters of genes that shouldn’t be active)
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1. Direct influence of TFs on assembly of initiation complexes Different molecular mechanisms of control of transcription initiation
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1. Direct influence of TFs on assembly of initiation complexes: interactions In general: some TFs interact with each other (or ligands or both) ; those interactions promote or prevent binding of GTFs this HLH monomer has no basic amino acids adjacent to the HLH motif this dimer cannot bind DNA; could
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25 - Transcription (Eukaryotes); Molecular Mechanisms -...

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