EPICENTROMERE

Determining the Epigenetic Mechanism of Centromere Propagation

Coordinatore	FUNDACAO CALOUSTE GULBENKIAN    more  Organization address address: AVENIDA DE BERNA 45A city: LISBOA postcode: 1000 contact info Titolo: Prof. Nome: António Cognome: Coutinho Email: send email Telefono: -4407550 Fax: -214410501
Nazionalità Coordinatore	Portugal [PT]
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-2007-4-3-IRG
Funding Scheme	MC-IRG
Anno di inizio	2008
Periodo (anno-mese-giorno)	2008-04-01   -   2012-03-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FUNDACAO CALOUSTE GULBENKIAN  Organization address address: AVENIDA DE BERNA 45A city: LISBOA postcode: 1000 contact info Titolo: Prof. Nome: António Cognome: Coutinho Email: send email Telefono: -4407550 Fax: -214410501	PT (LISBOA)	coordinator	0.00

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 Obiettivo del progetto (Objective)

'The centromere is a unique specialized chromatin domain responsible for the nucleation of the kinetochore, a large proteinaceous complex that, during mitosis, powers and controls chromosome movement on spindle microtubules ensuring accurate chromosome segregation, thereby preventing aneuploidy, a major hallmark of human cancers. Although directly embedded in chromatin no specific DNA sequence is either necessary or sufficient to propagate the centromere which is specified largely in an epigenetic manner. The primary candidate for centromere identification is CENP-A, a histone H3 variant that assembles specifically into centromeric nucleosomes and nucleates the assembly of the entire centromere complex. How this epigenetic “mark” is initiated and stably maintained while the underlying genome is continuously duplicated as cells divide remains a mystery. This is due, in part, to the inability to track proteins long term. I have adopted a novel fluorescent pulse labeling technique to specifically tackle this problem and established the basic long term dynamics of centromeric CENP-A chromatin. Here, I propose to build on these initial results and further develop this state-of-the-art fluorescent labeling technology combined with high-end imaging to determine how epigenetic factors are maintained and replenished across cell divisions using the centromere as a model while also expanding the analysis to include other epigenetic components. Through these new cell-biological tools in conjunction with molecular genetic and biochemical assays, I have devised a multifaceted approach to identify factors mediating CENP-A assembly as well as to determine the role of centromeric DNA in the initiation of the epigenetic mark. Collectively, these efforts are aimed at elucidating the general principles of epigenetic inheritance that are fundamental to transcription regulation, developmental programs and genome organization.'