title: The most redundant sequences in human CpG island library are derived from mitochondrial genome.
abstract: An altered pattern of epigenetic modifications, such as DNA methylation and histone modification, is critical to many common human diseases, including cancer. Recently, mitochondrial DNA (mtDNA) was reported to be associated with tumorigenesis through epigenetic regulation of methylation patterns. One of the promising approaches to study DNA methylation and CpG islands (CGIs) is sequencing and analysis of clones derived from the physical library generated by methyl-CpG-binding domain proteins and restriction enzyme MseI. In this study, we observed that the most redundant sequences of 349 clones in a human CGI library were all generated from the human mitochondrial genome. Further analysis indicated that there was a 5,845-bp DNA transfer from mtDNA to chromosome 1, and all the clones should be the products of a 510-bp MseI fragment, which contained a putative CGI of 270 bp. The 510-bp fragment was annotated as part of cytochrome c oxidase subunit II (COXII), and phylogenetic analysis of homologous sequences containing COXII showed three DNA transfer events from mtDNA to nuclear genome, one of which underwent secondary transfer events between different chromosomes. These results may further our understanding of how the mtDNA regulates DNA methylation in the nucleus.
authors.affiliation: CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Ximiao
authors.initials: X
authors.lastname: He
authors.forename: Shu
authors.initials: S
authors.lastname: Tao
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Songnian
authors.initials: S
authors.lastname: Hu
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D001482:Base Composition; D001483:Base Sequence; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D018899:CpG Islands; D003596:Cytosine / Q000032:analysis; D004247:DNA / Q000235:genetics; D019175:DNA Methylation; D004272:DNA, Mitochondrial / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics; D015723:Gene Library; D015894:Genome, Human; D054629:Genome, Mitochondrial; D006147:Guanine / Q000032:analysis; D006801:Humans; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D004272:DNA, Mitochondrial; D006147:Guanine; D003596:Cytosine; D004247:DNA; C117108:cytochrome C oxidase subunit II; D003576:Electron Transport Complex IV; C055927:endodeoxyribonuclease MseI; D015252:Deoxyribonucleases, Type II Site-Specific