title: Regional DNA methylation differences between humans and chimpanzees are associated with genetic changes, transcriptional divergence and disease genes.
abstract: Changes in gene expression have been proposed to have an important role in the evolutionary changes in phenotypes. Interspecific changes in gene expression can result not only from genetic changes in regulatory regions but also from epigenetic changes in such regions. Here we report the identification of genomic regions showing differences in DNA methylation between humans and chimpanzees (termed S-DMRs for species-specific differentially methylated regions) on chromosomes 21 and 22. These regional methylation differences are frequently associated with genes, including those relevant to a disease, such as Alzheimer's disease, diabetes mellitus or cancer. Methylation differences are often correlated with changes in promoter activity or alternative splicing. Comparative studies including other great ape species provide evidence for the contribution of genetic changes to some of these S-DMRs. Genetic changes responsible for the S-DMRs include gain or loss of CTCF-binding site and changes in CpG density in microsatellite repeats. Our results suggest that DNA methylation changes, often caused by small sequence changes, contribute to transcriptional and phenotypic diversification in hominid evolution.
authors.affiliation: Division of Epigenomics and Development, Medical Institute of Bioregulation, and Epigenome Network Research Center, Kyushu University, Fukuoka, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Fukuda
authors.forename: Kenji
authors.initials: K
authors.lastname: Ichiyanagi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Go
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Udono
authors.forename: Seitaro
authors.initials: S
authors.lastname: Wada
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Maeda
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Soejima
authors.forename: Naruya
authors.initials: N
authors.lastname: Saitou
authors.forename: Takashi
authors.initials: T
authors.lastname: Ito
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D002875:Chromosomes / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D016678:Genome; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA