FAME

FUNCTIONS OF CHROMATIN MARKS IN REGULATION OF GENE EXPRESSION

Coordinatore	INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH    more  Organization address address: ACKERMANNWEG 4 city: MAINZ postcode: 55128 contact info Titolo: Ms. Nome: Franziska Cognome: Martin Email: send email Telefono: +49 6131 39 21453 Fax: +49 6131 39 21421
Nazionalità Coordinatore	Germany [DE]
Totale costo	75˙000 €
EC contributo	75˙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)	2013-03-01   -   2016-02-29

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	INSTITUT FUR MOLEKULARE BIOLOGIE GGMBH  Organization address address: ACKERMANNWEG 4 city: MAINZ postcode: 55128 contact info Titolo: Ms. Nome: Franziska Cognome: Martin Email: send email Telefono: +49 6131 39 21453 Fax: +49 6131 39 21421	DE (MAINZ)	coordinator	75˙000.00

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 Obiettivo del progetto (Objective)

'In multicellular organisms, during embryogenesis and tissue homeostasis the differentiation of pluripotent stem cells into a variety of specialized cell types is governed by diverse transcriptional programs, the establishment and maintenance of which rely on epigenetic mechanisms, such as chromatin modifications. Over the past years, a large number of post-translational modifications of histones as well as enzymes responsible for either positioning or removal of these marks were characterized. Genome-wide studies mapping the distribution of histone modifications revealed a complex epigenetic landscape on eukaryotic chromosomes. In particular, distinct chromatin signatures were recently associated with enhancer elements, cis-acting DNA sequences inducing transcription from target promoters. However, whether the deposition of specific marks at enhancers is a pre-requisite for their activity or a mere consequence of the recruitment of histone-modifying complexes at their target promoters is an entirely open question. The aim of this proposal is to define the biological significance of histone modifications covering enhancer sequences in vivo. To perform this study we will generate transgenic mice allowing us to target histone-modifying activities at enhancers using a recently introduced technology based on transcription activator–like effectors (TALEs). The developing limb will serve as a model system since several well-defined enhancers are active specifically in this structure. We will validate this approach by assessing changes in histone marks over enhancer sequences in transgenic versus wild type mice. Next, we will determine how such changes affect the transcriptional status of the endogenous target gene of the enhancer by scoring both RNA levels and limb phenotypes. The results of this study are likely to have a major impact on our understanding of chromatin functions in transcriptional regulation.'