Novel genetic and epigenetic alterations in ... - Ous-research.no

Introductionmethylation during embryogenesis, and by such establish novel methylation marks on theDNA[8;26]. Some genes, including imprinted genes, are inherited via the germ line[27;28].How epigenetic information can be passed via germ cells is still unclear as a substantialepigenetic re-programming takes place during early embryogenesis, often thought of as anerasure of methylation marks.Promoter hypermethylation impair gene expression by preventing transcription factors tobind to DNA. This occurs in two ways, either by direct inhibition of the binding oftranscription factors to the methylated sequence[29;30], or via recruitment of proteins with amethyl binding domain (MBD protein family) which leads to condensation of the chromatinstructure by the means of histone deacetylation (reviewed in [31])(Figure 3). Knocking outMBD-proteins with RNA interference re-introduces transcription of initially inactive geneswithout altering the methylation status, thereby clearly demonstrating the role of MBDs as alink between promoter hypermethylation and gene expression[32]. Still, the role of mutationsin either of the MBD genes are unclear[33;34].16