Identification of regulatory elements responsible for genomic imprinting in mammals

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Imprinted genes are preferentially or exclusively expressed from only one of the parental alleles. The silencing of one allele involves epigenetic mechanisms of gene regulation such as DNA methylation and chromatin (histone) modifications. The goal of the proposed project is to identify and characterize genetic and epigenetic elements which control imprinting and to understand their mechanistics. For this purpose we will work on two different gene clusters that are affected by genomic imprinting in mouse: the Beckwith-Wiedemann syndrome (BWS) region on distal chromosome 7 and the Dlk1-Gtl2 region on distal chromosome 12. On chr. 7 the project will focus on the functional analysis of a non-coding transcript residing in a region important for imprinting control in the Kcnq1 gene and on the investigation of imprinting in extraembryonic tissues since here mechanisms of imprinting control appear to be different from embryonic tissues. The Dlk1-Gtl2 region shares similarities with the Igf2-H19 genes in the BWS region. We will identify and study new imprinted genes and differentially methylated elements downstream of Gtl2. This will show if imprinting control in this region shares structural and functional similarities to the BWS region or other imprinted domains. In connection with the functional studies we will pursue genome-wide comparative computational analyses to identify specific sequence and structural features in these imprinted regions and their possible application to characterize other imprinted domains and to identify new imprinted genes.