The role of paternal histone methylation in transgenerational inheritance and epigenetic memory

• Antragstellerin: Dr. Nathalie Véron
• Fachliche Zuordnung: Allgemeine Genetik und funktionelle Genomforschung
• Förderung: Förderung von 2010 bis 2012
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 172488978

Through the modulation of chromatin states, epigenetic mechanisms contribute to the reading of genetic information. Classically, epigenetic regulators are known to play a conserved role in the heritability of cell identity during somatic differentiation and in genome stability suggesting that post-translational histone modifications contribute to epigenetic memory. During sperm differentiation most of the histone-containing nucleosomes are replaced by basic protamines that allow tight compaction of the DNA in the sperm nucleus. Interestingly, histones detected in mammalian sperm bear post-translational modifications, e.g. active histone H3 lysine 4 dimethylation (H3K4me2) and repressive histone H3 lysine 27 trimethylation (H3K27me3), which localize to specific sites in the haploid genome. Whereas the K3K4me2 mark is predominantly localized at promoters of genes functioning in spermatogenesis and cellular homeostasis, H3K27me3 marks promoters of key developmental regulators in sperm as in soma. Repression of H3K27me3-marked genes during spermatogenesis and early embryogenesis suggests a role of paternally provided H3K27me3 in epigenetic memory across generations. In this application I propose to study the function of the paternally transmitted repressive H3K27me3 mark in embryonic development by using a molecular genetic approach. I will assess changes in gene expression in embryos that develop upon fertilization of wild-type oocytes with H3K27me3- deficient sperm in a genome-wide and parental-specific manner using microarray and deep-sequencing methods.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: Schweiz
• Gastgeber: Professor Dr. Antoine Peters