COACTIVATOR

Regulation of gene expression by transcriptional coactivators

Coordinatore	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE    more  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Dr. Nome: Jocelyn Cognome: Mere Email: send email Telefono: +33 4 67613535 Fax: +33 4 67043236
Nazionalità Coordinatore	France [FR]
Totale costo	100˙000 €
EC contributo	100˙000 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2012-CIG
Funding Scheme	MC-CIG
Anno di inizio	2013
Periodo (anno-mese-giorno)	2013-12-01   -   2017-11-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE  Organization address address: Rue Michel -Ange 3 city: PARIS postcode: 75794 contact info Titolo: Dr. Nome: Jocelyn Cognome: Mere Email: send email Telefono: +33 4 67613535 Fax: +33 4 67043236	FR (PARIS)	coordinator	100˙000.00

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 Obiettivo del progetto (Objective)

'How a cell responds to developmental or environmental changes by altering gene expression is a fundamental question in biology. One critical level of regulation is transcription initiation, which is controlled by large multiprotein complexes, including coactivators. Many studies have shown that coactivators have distinct activities that play crucial roles in transcription, and their perturbation can cause cancer or neurodegeneration. Little is known, however, about how these activities integrate external signals to control transcription. I have established one such coactivator, the highly conserved SAGA complex, as an excellent model to address this question. First, I discovered that, in the fission yeast Schizosaccharomyces pombe, SAGA regulates the switch from proliferation to differentiation. SAGA uses distinct activities to function either as a repressor or as an activator of differentiation genes, depending on the levels of extracellular nutrients. Second, I discovered that S. pombe provides a unique opportunity to study the function of the largest SAGA subunit, Tra1. Its mammalian homolog, TRRAP, is a key regulator of early embryogenesis and oncogenesis. My overall objective is to address key issues in the regulation of gene expression by focusing on SAGA, using a combination of genetic, genomic, biochemical, and proteomic approaches. One goal of this proposal is to identify which nutrient-sensing signaling pathway causes SAGA to switch from a repressor to an activator at the promoters of differentiation genes. A second objective is to address the role of Tra1 in coordinating the activity of kinases sensing various cellular stresses and the regulatory roles of transcriptional coactivators. Overall, these studies will illuminate previously unknown mechanisms for the control of transcription by signal transduction pathways in eukaryotes.'