Final Activity Report Summary - EPIGENETIC REGULATIO (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 epigenetic 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 established 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, this on-going project aims to unravel the nature of the imprints at the sequence elements that control imprinting (the imprinting-control centres). It examines which features of the DNA sequences at imprinting-control centres are essential for the initiation of this process. 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 are investigated at representative imprinted loci, by coupling chromatin immuno-precipitation with bisulphite genomic sequencing, during the resetting and acquisition of the imprints in the germ cell lineage. First insights from these exploratory analyses enabled us to design a targeting approach that will tests for functional significance a candidate region potentially important for the acquisition of the imprint.
Results obtained will enhance our general understanding of the developmental regulation of gene expression in mammals. They will help also, to elucidate the underlying cause(s) of human diseases caused by alterations in epigenetic patterns, including mental retardation, growth syndromes, and cancer.
Using the mouse as a model, this on-going project aims to unravel the nature of the imprints at the sequence elements that control imprinting (the imprinting-control centres). It examines which features of the DNA sequences at imprinting-control centres are essential for the initiation of this process. 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 are investigated at representative imprinted loci, by coupling chromatin immuno-precipitation with bisulphite genomic sequencing, during the resetting and acquisition of the imprints in the germ cell lineage. First insights from these exploratory analyses enabled us to design a targeting approach that will tests for functional significance a candidate region potentially important for the acquisition of the imprint.
Results obtained will enhance our general understanding of the developmental regulation of gene expression in mammals. They will help also, to elucidate the underlying cause(s) of human diseases caused by alterations in epigenetic patterns, including mental retardation, growth syndromes, and cancer.