EPIMECHANISM

Mechanisms of Chromatin-based Epigenetic Inheritance

Coordinatore	FUNDACAO CALOUSTE GULBENKIAN    more Spiacenti, non ci sono informazioni su questo coordinatore. Contattare Fabio per maggiori infomrazioni, grazie.
Nazionalità Coordinatore	Portugal [PT]
Totale costo	1˙621˙400 €
EC contributo	1˙621˙400 €
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-2013-CoG
Funding Scheme	ERC-CG
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-06-01   -   2019-05-31

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FUNDACAO CALOUSTE GULBENKIAN  Organization address address: AVENIDA DE BERNA 45A city: LISBOA postcode: 1000 contact info Titolo: Dr. Nome: Lars Cognome: Jansen Email: send email Telefono: +35 1 214464519 Fax: +35 1 214407970	PT (LISBOA)	hostInstitution	1˙621˙400.00
2	FUNDACAO CALOUSTE GULBENKIAN  Organization address address: AVENIDA DE BERNA 45A city: LISBOA postcode: 1000 contact info Titolo: Mr. Nome: Jose Mario Cognome: Leite Email: send email Telefono: +35 1 214407937 Fax: 351214000000	PT (LISBOA)	hostInstitution	1˙621˙400.00

Mappa

 Word cloud

Esplora la "nuvola delle parole (Word Cloud) per avere un'idea di massima del progetto.

 Obiettivo del progetto (Objective)

'Epigenetic mechanisms heritably maintain gene expression states and chromosome organization across cell division. These include chromatin-based factors that are propagated independent of local DNA sequence elements, and are critical for normal development and prevent reprogramming, e.g. during induction of pluripotency. We focus on the role of nucleosomes, the histone-DNA complexes that make up chromatin. While prominently implicated in epigenetic memory, how histones and their local modifications can actually be inherited is largely unknown. We take aim at three fundamental aspects that we argue are central to this problem: stability of the epigenetic mark, self-templated duplication, and cell cycle coupling. We developed a unique pulse-labeling strategy to determine whether silent and active chromatin can be inherited and how this relates to transcription, both in cancer cells and in vitro differentiating stem cells. By coupling this strategy to an imaging-based RNAi screen we aim to identify components controlling nucleosome assembly and heritability. We achieve this by focusing on the human centromere, the chromosome locus essential for chromosome segregation which serves as an ideal model for epigenetic memory. This locus is specified by nucleosomes carrying the histone H3 variant, CENP-A that we have previously shown to be highly stable in cycling cells and to be replicated in a strict cell cycle coupled manner. We build on our previous successes to uncover the molecular mechanism and cellular consequences of the coupling between CENP-A propagation and the cell cycle which we postulate, ensures proper centromere size and mitotic fidelity. Furthermore, by genome engineering we developed a strategy to delete an endogenous centromere to determine how centromeres can form de novo and how CENP-A chromatin, once formed, can template its own duplication. With this multi-facetted approach we aim to uncover general mechanistic principles of chromatin-based memory.'