Long-range Control of Gene Expression by Imprinting Control Regions During Development and Neoplasia

摘要: Genomic imprinting is an epigenetic phenomenon by which a subset of genes expressed in parent origin specific manner. Most the imprinted are located clusters. Genetic evidences suggest that clusters regulated Imprinting Control Regions (ICRs). To elucidate mechanisms maintained clusters, we have chosen well characterized cluster at distal end mouse chromosome 7. This contains 15 and they been shown to be H19 Kcnq1 ICRs. The ICR, chromatin insulator function, implicated regulation Igf2 interacting with CTCF protein. It has documented also involved maintenance differential methylation ICR. In this investigation demonstrated lost when subjected ICR containing episomal plasmids de novo machinery human choriocarcinoma cell line, JEG3, suggesting looses its privilege property under neoplastic conditions. 11 genes. methylated on active maternal allele but unmethylated inactive paternal overlaps oppositely oriented paternally gene known as Kcnq1ot1. investigation, controls neighboring behaving bidirectional silencer function antisense RNA Furthermore, duration transcription plays critical role RNA- mediated silencing. conclusion, thesis provides more insights into complex mechanistic aspects ICRs, control during development neoplasia.