Swedish University of Agricultural Sciences, Sweden
Title: Epigenetic regulation of the Igf2/H19 gene cluster - Prospects for novel therapeutic traits
Wilhelm Engstrom received his Ph.D. and M.D. from Karolinska Indstitutet. He worked as a postdoctoral fellow at University of Oxford for eight years before he was appointed professor of general pathology at the Faculty of Veterinary Medicine, Uppsala Sweden. He is the current president of the European Cell Proliferation Society, a fellow of the Royal Uppsala Society of Sciences and a fellow of the Royal College of Pathologists (U.K.).
The Igf2 (insulin-like growth factor 2) and H19 genes are imprinted in mammals. Igf2 is a growth factor expressed in most normal tissues solely from the paternal allele. In contrast, the H19 gene is transcribed (but not translated to a protein) from the maternal allele. The Igf2 protein is a growth factor particularly important during pregnancy, where it promotes both fetal and placental growth and also nutrient placental transfer from mother to offspring. The epigenetic regulation of the Igf2/H19 gene-cluster leads to parent-specific expression, with current models including parental allele-specific DNA methylation and chromatin modifications, DNA-binding of insulator proteins (CTCFs) and the three-dimensional partitioning of DNA in the nucleus. The enhancer competition model, the boundary model, and the chromatin-loop model are three models based on differential methylation as the epigenetic mark responsible for the imprinted expression pattern. Pathways will be discussed that can account for the allelic methylation differences, as there is a recent study that contradicts the previously accepted fact that biallelic expression is accompanied with loss of the differential methylation-pattern. These models provide novel concepts for the development of new therapeutic traits in human cancer.