DYNAMIC-TRANS-COMPS · Transcriptional regulatory complexes: dynamic functional interplay in vivo and structural organisation

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Project objective

The objective of this proposal is to understand the function and structure of the transcription regulatory complexes (TFIID, B-TFIID, CCR4-Not, NC2, PC4, and PC6) that modulate both positively and negatively RNA polymerize II transcription. The respective roles of each complex in programming gene expression patterns during growth and development will be addressed in vivo and the molecular mechanisms underlying their activity will be studied by functional in vitro assays. Focus will be placed on the dynamic interplay between complexes, the identification of target genes their structural organization, and how post-translational modifications modulate stability and activity of their constituent subunits. Our collaborative approach will exploit yeast and mammalian genetic models along with biochemical and biophysical studies.Specific aims include:1 . Analysis of genetic interactions between the above factors in vivo in yeast and mutant mice/mammalian cell lines. Physical interactions in vitro through biochemical studies with the respective complexes and/or their subunits.2 . Characterization of the respective roles of each complex in vivo and identification of target genes by chromatin immunoprecipitation and analysis of knock out lines/strains.3 . Analysis of interplay between factors during growth and differentiation via yeast/mammalian genetic models and in vitro.4. Investigation of transcription factor regulation through changes in subunit stability induced by sumoylation/ubiquitination.5. Electron microscopy of the B-TFIID and CCR4-Not complexes. Understanding the organization, function, and interplay of transcription factor complexes is a major challenge in modern biology. The strength of our network to tackle these questions lies in the multidisciplinary expertise of the constituent groups and their ability to address different aspects of the problem. This integrated approach will deliver important new contributions to understand

Original text from CORDIS.

Participants

• CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE · PARISCoordinatorFrance
• CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE · PARISFrance
• GSF-RESEARCH CENTER FOR ENVIRONMENT AND HEALTH · OBERSCHLEISSHEIMGermany
• MARIE CURIE CANCER CARE · OXYEDCountry levelUnited Kingdom
• UNIVERSITY MEDICAL CENTRE UTRECHT · UTRECHTNetherlands
• UNIVERSITY OF GENEVA · GENEVESwitzerland
• UNIVERSITY OF UMEAA · UMEAASweden

Links

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