Spring 09 lecture 24

Spring 09 lecture 24 - Roeder, R.G. (2005) Transcriptional...

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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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Different molecular mechanisms of control of transcription initiation 1. Direct influence of TFs on assembly of initiation complexes (review): TFs help recruitment of GTFs, interactions of TFs with modulator complex, co-activators (or co-repressors), each other, ligands & promote or prevent 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 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: recruitment of GFTs Eukaryotes : RNAP is not directly recruited – TFs act through contact with GTF In steps - TFIID complex binds first due to interactions of TAFs with activator(s) bound to the enhancer(s)… Weaver: Molecular Biology Two models: As a holoenzyme –RNAPII and some GTFs recruited into complex (at least some yeast promoters) and mediators and mediator
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1. Direct influence of TFs on assembly of initiation complexes: co-activators Certain TFs need their own co-activator protein – protein which is not in direct contact with DNA but connects TF with GTFs Example: cAMP response element binding protein (CREB) binds to cAMP response element (CRE) and activates associated genes by binding to CREB - binding protein (CBP) which interacts with basal complex CBP is not limited to cAMP responsive genes – it has multiple functions (e.g. has acetyltransferase activity)
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1. Direct influence of TFs on assembly of initiation complexes: interactions TFs interact with co-factors or each other; 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 not interact with the response element → no functional activator binding could result in less/no expression (Lewin, 2006. Fig. this could be a dimer that forms a functional activator protein
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1. Direct influence of TFs on assembly of initiation complexes: interactions; several ways in which eukaryotic repressors work : repressor can inhibit gene activation by binding to site that overlaps activator binding site (derivative incapable of DNA binding replaces activator → inactive heterodimer – previous slide ) repressor protein binds at site adjacent to activator site and interferes with AD of activator repressor binds upstream,
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This note was uploaded on 08/03/2009 for the course BIOL BIOL308 taught by Professor Miskovic during the Spring '09 term at Waterloo.

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Spring 09 lecture 24 - Roeder, R.G. (2005) Transcriptional...

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