NUCLEOSOME RETENTION

Dissecting the Mechanism of Nucleosome Retention in Mouse Spermatozoa

Coordinatore	FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH    more  Organization address address: MAULBEERSTRASSE 66 city: BASEL postcode: 4058 contact info Titolo: Mrs. Nome: Dorothy Cognome: Searles Email: send email Telefono: +41 616972982 Fax: +41 616973976
Nazionalità Coordinatore	Switzerland [CH]
Totale costo	207˙928 €
EC contributo	207˙928 €
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-2013-IEF
Funding Scheme	MC-IEF
Anno di inizio	2015
Periodo (anno-mese-giorno)	2015-03-01   -   2017-03-19

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH  Organization address address: MAULBEERSTRASSE 66 city: BASEL postcode: 4058 contact info Titolo: Mrs. Nome: Dorothy Cognome: Searles Email: send email Telefono: +41 616972982 Fax: +41 616973976	CH (BASEL)	coordinator	207˙928.80

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 Obiettivo del progetto (Objective)

'Studies in mice and men suggest that changes in environmental conditions such as nutrition, exposure to environmental pollutants or parental care during early postnatal life can affect the development, physiology and fitness of offspring. The epigenetic mechanisms underlying the transmission of such traits over one or multiple generations are largely unknown but DNA methylation, RNA and nucleosomes have been proposed as mediators of such inheritance. At the end of male germ cell development chromatin is extensively remodeled, resulting in a highly compact nuclear architecture in spermatozoa that is compatible with fertilization. During this process, most but not all nucleosomes are removed and replaced by protamines. The host laboratory recently demonstrated retained nucleosomes localize at CpG islands of the genome that are present within regulatory regions of genes, suggesting that these regions may confer epigenetic inheritance between generations. Preliminary data implicate different histone H3 variants and modifications in the nucleosome eviction and retention process. Here I aim at dissecting the mechanism of nucleosome retention in mouse sperm. Using a quantitative biochemical approach, I will test the possibility that nucleosome retention at CpG islands is an indirect consequence of high intrinsic affinities of protamines for GC-poor DNA. I will determine the composition of evicted versus retained nucleosomes in terms of histone variants and post-translational modifications, by performing immunoprecipitation coupled to mass spectrometry. Importantly, I will investigate whether nucleosome retention is controlled by a “retention factor” using a mass spectrometry approach combined with cellular and genetic assays. The proposed research will provide mechanistic insights into the mechanisms of nucleosome retention during spermatogenesis, thereby laying the foundations for further functional studies in nucleosome-based paternal epigenetic inheritance.'