In several of the affected tissues, the two imprinted genes appear to act in an antagonistic manner, a finding that may help explain how BWS may result from mutations in either gene. Our studies into the mechanism of gene silencing of imprinted genes have led us to conclude that there are multiple mechanisms at work. Genes such as the H19 gene, which is expressed exclusively from the maternal chromosome, are silenced by DNA methylation that is inherited from the paternal germline. Igf2, on the other hand, is silenced indirectly through an element that blocks the interaction of the gene with enhancers that lie 100 kilobases away. This enhancer blocker is inactivated by DNA methylation on the paternal chromosome, allowing for expression of the Igf2 gene.
Enhancer blockers only function when placed between a gene and an enhancer.
Such elements help explain how imprinted genes can be imprinted in some tissues but not in others, as imprinting will depend on the position of transcriptional regulatory elements relative to the epigenetic control region. During embryogenesis, neural crest cells arise from the dorsal end of the closing neural tube. These cells are pluripotent, giving rise to a wide range of cell types, including neurons and glia of the peripheral nervous system, craniofacial bones and cartilage, smooth muscle cells, and melanocytes. Upon their emergence from the neural tube, neural crest cells undergo extensive proliferation as they migrate along distinct pathways to destinations where they differentiate into specific lineages. To understand the role of Ednrb in development, we generated a mutant mouse in which the bacterial lacZ gene is expressed in place of Ednrb, providing us with an easy way to visualize its expression in vivo .