ACCOMPLI

Assembly and maintenance of a co-regulated chromosomal compartment

Coordinatore	LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Germany [DE]
Totale costo	2˙482˙770 €
EC contributo	2˙482˙770 €
Programma	FP7-IDEAS-ERC Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	ERC-2011-ADG_20110310
Funding Scheme	ERC-AG
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-02-01   -   2017-01-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN  Organization address address: GESCHWISTER SCHOLL PLATZ 1 city: MUENCHEN postcode: 80539 contact info Titolo: Mr. Nome: Brice Cognome: Rousseau Email: send email Telefono: +49 89 2180 72274 Fax: +49 89 2180 2985	DE (MUENCHEN)	hostInstitution	2˙482˙770.00
2	LUDWIG-MAXIMILIANS-UNIVERSITAET MUENCHEN  Organization address address: GESCHWISTER SCHOLL PLATZ 1 city: MUENCHEN postcode: 80539 contact info Titolo: Prof. Nome: Peter Burkhard Cognome: Becker Email: send email Telefono: +49 89 2180 75427 Fax: +49 89 2180 75425	DE (MUENCHEN)	hostInstitution	2˙482˙770.00

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 Obiettivo del progetto (Objective)

'Eukaryotic nuclei are organised into functional compartments, – local microenvironments that are enriched in certain molecules or biochemical activities and therefore specify localised functional outputs. Our study seeks to unveil fundamental principles of co-regulation of genes in a chromo¬somal compartment and the preconditions for homeostasis of such a compartment in the dynamic nuclear environment. The dosage-compensated X chromosome of male Drosophila flies satisfies the criteria for a functional com¬partment. It is rendered structurally distinct from all other chromosomes by association of a regulatory ribonucleoprotein ‘Dosage Compensation Complex’ (DCC), enrichment of histone modifications and global decondensation. As a result, most genes on the X chromosome are co-ordinately activated. Autosomal genes inserted into the X acquire X-chromosomal features and are subject to the X-specific regulation. We seek to uncover the molecular principles that initiate, establish and maintain the dosage-compensated chromosome. We will follow the kinetics of DCC assembly and the timing of association with different types of chromosomal targets in nuclei with high spatial resolution afforded by sub-wavelength microscopy and deep sequencing of DNA binding sites. We will characterise DCC sub-complexes with respect to their roles as kinetic assembly intermediates or as representations of local, functional heterogeneity. We will evaluate the roles of a DCC- novel ubiquitin ligase activity for homeostasis. Crucial to the recruitment of the DCC and its distribution to target genes are non-coding roX RNAs that are transcribed from the X. We will determine the secondary structure ‘signatures’ of roX RNAs in vitro and determine the binding sites of the protein subunits in vivo. By biochemical and cellular reconstitution will test the hypothesis that roX-encoded RNA aptamers orchestrate the assembly of the DCC and contribute to the exquisite targeting of the complex.'