GRPN

Gene Regulation at the Nuclear Periphery

Coordinatore	THE UNIVERSITY OF EDINBURGH    more  Organization address address: OLD COLLEGE, SOUTH BRIDGE city: EDINBURGH postcode: EH8 9YL contact info Titolo: Ms. Nome: Angela Cognome: Noble Email: send email Telefono: +44 131 6509024 Fax: +44 131 651 4028
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	180˙103 €
EC contributo	180˙103 €
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-2009-IEF
Funding Scheme	MC-IEF
Anno di inizio	2010
Periodo (anno-mese-giorno)	2010-08-01   -   2012-07-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	THE UNIVERSITY OF EDINBURGH  Organization address address: OLD COLLEGE, SOUTH BRIDGE city: EDINBURGH postcode: EH8 9YL contact info Titolo: Ms. Nome: Angela Cognome: Noble Email: send email Telefono: +44 131 6509024 Fax: +44 131 651 4028	UK (EDINBURGH)	coordinator	180˙103.20
2	MEDICAL RESEARCH COUNCIL  Organization address address: NORTH STAR AVENUE POLARIS HOUSE city: SWINDON postcode: SN2 1FL contact info Titolo: Prof. Nome: Wendy Cognome: Bickmore Email: send email Telefono: +44 131 332 2471 Fax: +44 131 467 8456	UK (SWINDON)	participant	0.00

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 Obiettivo del progetto (Objective)

'The spatial organisation of the genome in the nucleus has a role in the regulation of gene expression. In vertebrates, chromosomal regions with low gene-density, and that are less transcribed, are located close to the nuclear periphery. Correlations have also been made between the transcriptional state of some genes and their location near the nuclear periphery. For example, the proneural Mash1 gene relocates away from the nuclear periphery when it is activated during neural differentiation of mouse embryonic stem (ES) cells. Recently, the host laboratory demonstrated that the nuclear periphery plays a direct role in gene repression by experimentally relocating genomic loci to the nuclear envelope. A crucial issue is whether this nuclear reorganisation is important for correct differentiation and development. To do this I will impair the relocation of Mash1 in ES cells by tethering it to the nuclear envelope with the lacO/lacI-lap2b system set up in the host laboratory. The consequences of this anchoring on Mash1 transcription and neural cell differentiation will be assessed. I also propose to investigate the mechanism of Mash1 relocation. First I will determine whether the nuclear position of Mash1 influences its chromatin state, by establishing the histone modifications of the locus, when tethered or not. Then I will address whether nuclear reorganisation is an active or passive process. In live cells, I will track the position of the lacO tagged Mash1 visualized with lacI fused to GFP, during neural differentiation. Finally, I will determine the endogenous pathways that retain specific loci at the nuclear periphery. I will perform two high-throughput screens on a human cell line established in the lab where a peripheral locus is visualized by laco/lacI-GFP. An siRNA screen and a small molecule screen will be used to look for factors whose loss or inhibition lead to displacement of the lacO-tagged locus away from the nuclear edge.'