Genomic imprinting: significance in development and diseases and the molecular mechanisms

Certain mammalian genes are expressed exclusively from either the paternal or the maternal chromosome because of a differential marking process that occurs during gametogenesis. This epigenetic marking is called genomic imprinting. Monoallelic expression of imprinted genes is responsible for the inability of uniparental mammalian embryos to develop normally and for the abnormal phenotypes observed with particular chromosomal disomies. Many of the imprinted genes identified to date are involved in the regulation of cell proliferation and differentiation and, together with other pieces of evidence, they are suggested to play a role in tumorigenesis. Here we discuss how imprinted genes cause diseases and tumors and summarize the recent advances of studies on the molecular basis of this epigenetic phenomenon. In particular, we focus on two well-characterized imprinted chromosomal regions, namely the human Prader-Willi/Angelman syndrome region and the mouse INS2/IGF2/H19 region. The correlations between the differential gene activity and the changes in DNA methylation, higher order chromatin structure and replication timing, will shed light on gene regulation at the level of the chromosomal domain.