title: 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 from human and mouse by in silico analyses. We have found that the human genome does not only contain more CGIs than the mouse, but the proportion of intronic CGIs is also higher (7.7% vs. 3.5%). At least 2,033 human intronic CGIs are not present in the mouse. 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. Four CGIs, which are located in the RB1, ASRGL1, PARP11, and PDXDC1 genes, occur as methylated and unmethylated copies. In contrast to imprinted methylation at the RB1 locus, differential methylation of the ASRGL1 and PDXDC1 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.
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Rademacher
authors.affiliation: Genominformatik, Institut für Humangenetik, Medizinische Fakultät, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Christopher
authors.initials: C
authors.lastname: Schröder
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Deniz
authors.initials: D
authors.lastname: Kanber
authors.affiliation: BioChip Labor, Institut für Zellbiologie, Medizinische Fakultät, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Klein-Hitpass
authors.affiliation: Institut für Klinische Chemie und Laboratoriumsmedizin, Universitätsklinikum Regensburg, Universität Regensburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wallner
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Zeschnigk
authors.affiliation: Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany bernhard.horsthemke@uni-due.de.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D019143:Evolution, Molecular; D018392:Genomic Imprinting; D005838:Genotype; D007438:Introns / Q000235:genetics; D006801:Humans
keywords: CpG islands; epigenetics; evolution; methylation; retrocopy