Tandem B1 elements located in a mouse methylation center provide a target for de novo DNA methylation

A cis-acting methylation center that signals de novo DNA methylation is loc ated upstream of the mouse Aprt gene. In the current study, two approaches were taken to determine if tandem B1 repetitive elements found at the 3' en d of the methylation center contribute to the methylation signal. First, bi sulfite genomic sequencing demonstrated that CpG sites within the B1 elemen ts were methylated at relative levels of 43% in embryonal stem cells defici ent for the maintenance DNA methyltransferase when compared with wild type embryonal stem cells. Second, the ability of the BI elements to signal de n ovo methylation upon stable transfection into mouse embryonal carcinoma cel ls was examined, This approach demonstrated that the B1 elements were methy lated de novo to a high level in the embryonal carcinoma cells and that the B1 elements acted synergistically, The results from these experiments prov ide strong evidence that the tandem B1 repetitive elements provide a signif icant fraction of the methylation center signal. By extension, they also su pport the hypothesis that one role for DNA methylation in mammals is to pro tect the genome from expression and transposition of parasitic elements.