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Content archived on 2024-05-29

Acquisition and regulation of epigenetic marks in mammals


Epigenetic mechanisms are essential in the programme of mammalian embryogenesis and postnatal development. Not surprisingly, therefore, their pathological deregulation can lead to human diseases and may be involved in cancer formation. A well-known epigene tic phenomenon in mammals is genomic imprinting, a mechanism via which certain autosomal genes show parental allele-specific expression. To accomplish this mono-allelic expression, imprinted genes present epigenetic marks ('the imprints') that are establis hed in either the male, or the female, germ line. These imprints are propagated from sperm, or egg, to the developing embryo, and are essential for imprinted gene expression, and hence, for normal development and health. Using the mouse as a model, the pro ject will unravel the nature of the imprints at the sequence elements that control imprinting ('the imprinting-control centres'). It will examine which features of the DNA sequences at imprinting-control centres are essential for the initiation of this pro cess. The Project focuses on the involvement of histone methylation at imprinting-control centres, and on methylation of CpG dinucleotides in the DNA. These epigenetic modifications will be investigated at representative imprinted loci, by coupling chromat in immuno-precipitation with bisulphite genomic sequencing, during the resetting and acquisition of the imprints in the germ cell lineage. Insights from these exploratory analyses will lead to tests for functional significance using transgenic approaches. This project complements and extends the researcher's experience in epigenetics acquired during his period of mobility. It will benefit both from the researcher's expertise in the analysis of DNA methylation in the germ line, and from the reintegration hos t's leading edge on the role of chromatin in imprinting. New insights resulting from this project will form the basis for a long-term program that will be undertaken through permanent #

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