Evolutionary origin and methylation status of human intronic CpG islands that are not present in mouse

Abstract

Imprinting of the human RB1 gene is due to the presence of a differentially methylated CpG island (CGI) in intron 2,which is part of a retrocopy derived from the PPP1R26 gene on chromosome 9. The murine Rb1 gene does not have this retrocopy and is not imprinted. We have investigated whether the RB1/Rb1 locus is unique with respect to these differences. For this, we have compared the CGIs fromhumanandmouse by in silico analyses.Wehave found that thehumangenomedoes not only containmoreCGIs than themouse,but theproportionof intronicCGIs is alsohigher (7.7%vs.3.5%).At least2,033human intronic CGIs arenot present in themouse. Among these CGIs, 104 show sequence similarities elsewhere in the human genome,which suggests that they arose from retrotransposition. We could narrow down the time points when most of these CGIs appeared during evolution. Their methylation status was analyzed in two monocyte methylome data sets from whole-genome bisulfite sequencing and in 18 published methylomes. FourCGIs, which are located in the RB1, ASRGL1, PARP11, andPDXDC1 genes, occur asmethylated and unmethylated copies. In contrast to imprintedmethylation at the RB1 locus, differentialmethylation of the ASRGL1 andPDXDC1 CGIs appears to be sequence dependent. Our study supports the notion that the epigenetic fate of the retrotransposed DNA depends on its sequence and selective forces at the integration site. © The Author(s) 2014.