title: Genome-wide methylation analysis of retrocopy-associated CpG islands and their genomic environment.
abstract: Gene duplication by retrotransposition, i.e., the reverse transcription of an mRNA and integration of the cDNA into the genome, is an important mechanism in evolution. Based on whole-genome bisulfite sequencing of monocyte DNA, we have investigated the methylation state of all CpG islands (CGIs) associated with a retrocopy (n = 1,319), their genomic environment, as well as the CGIs associated with the ancestral genes. Approximately 10% of retrocopies are associated with a CGI. Whereas almost all CGIs of the human genome are unmethylated, 68% of the CGIs associated with a retrocopy are methylated. In retrocopies resulting from multiple retrotranspositions of the same ancestral gene, the methylation state of the CGI often differs. There is a strong positive correlation between the methylation state of the CGI/retrocopy and their genomic environment, suggesting that the methylation state of the integration site determined the methylation state of the CGI/retrocopy, or that methylation of the retrocopy by a host defense mechanism has spread into the adjacent regions. Only a minor fraction of CGI/retrocopies (n = 195) has intermediate methylation levels. Among these, the previously reported CGI/retrocopy in intron 2 of the RB1 gene (PPP1R26P1) as well as the CGI associated with the retrocopy RPS2P32 identified in this study carry a maternal methylation imprint. In conclusion, these findings shed light on the evolutionary dynamics and constraints of DNA methylation.
authors.affiliation: a Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen , Essen , Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Grothaus
authors.affiliation: a Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen , Essen , Germany.
authors.forename: Deniz
authors.initials: D
authors.lastname: Kanber
authors.affiliation: b Klinik für Frauenheilkunde und Geburtshilfe, Universitätsklinikum Essen , Essen , Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Gellhaus
authors.affiliation: a Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen , Essen , Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Mikat
authors.affiliation: c Institut für Humangenetik, Christian-Albrechts-Universität Kiel & Universitätsklinikum Schleswig-Holstein , Campus Kiel, Kiel , Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Kolarova
authors.affiliation: c Institut für Humangenetik, Christian-Albrechts-Universität Kiel & Universitätsklinikum Schleswig-Holstein , Campus Kiel, Kiel , Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.affiliation: a Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen , Essen , Germany.
authors.forename: Dagmar
authors.initials: D
authors.lastname: Wieczorek
authors.affiliation: a Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen , Essen , Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Horsthemke
mesh_terms: D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D015894:Genome, Human; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D007438:Introns / Q000235:genetics; D000072741:Maternal Inheritance / Q000235:genetics; D009000:Monocytes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D056286:Retinoblastoma Binding Proteins / Q000235:genetics*; D018626:Retroelements / Q000235:genetics; D017422:Sequence Analysis, DNA; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C000606393:RB1 protein, human; D056286:Retinoblastoma Binding Proteins; D018626:Retroelements; D044767:Ubiquitin-Protein Ligases
keywords: CpG islands; DNA methylation; RPS2P32; imprinting; retrotransposition