title: Methylation and expression analyses of the 7q autism susceptibility locus genes MEST , COPG2, and TSGA14 in human and anthropoid primate cortices.
abstract: The autism susceptibility locus on human chromosome 7q32 contains the maternally imprinted MEST and the non-imprinted COPG2 and TSGA14 genes. Autism is a disorder of the 'social brain' that has been proposed to be due to an overbalance of paternally expressed genes. To study regulation of the 7q32 locus during anthropoid primate evolution, we analyzed the methylation and expression patterns of MEST, COPG2, and TSGA14 in human, chimpanzee, Old World monkey (baboon and rhesus macaque), and New World monkey (marmoset) cortices. In all human and anthropoid primate cortices, the MEST promoter was hemimethylated, as expected for a differentially methylated imprinting control region, whereas the COPG2 and TSGA14 promoters were completely demethylated, typical for transcriptionally active non-imprinted genes. The MEST gene also showed comparable mRNA expression levels in all analyzed species. In contrast, COPG2 expression was downregulated in the human cortex compared to chimpanzee, Old and New World monkeys. TSGA14 either showed no differential regulation in the human brain compared to chimpanzee and marmoset or a slight upregulation compared to baboon. The human-specific downregulation supports a role for COPG2 in the development of a 'social brain'. Promoter methylation patterns appear to be more stable during evolution than gene expression patterns, suggesting that other mechanisms may be more important for inter-primate differences in gene expression.
authors.affiliation: Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Schneider
authors.forename: S
authors.initials: S
authors.lastname: Mayer
authors.forename: N
authors.initials: N
authors.lastname: El Hajj
authors.forename: L R
authors.initials: LR
authors.lastname: Jensen
authors.forename: A W
authors.initials: AW
authors.lastname: Kuss
authors.forename: H
authors.initials: H
authors.lastname: Zischler
authors.forename: I
authors.initials: I
authors.lastname: Kondova
authors.forename: R E
authors.initials: RE
authors.lastname: Bontrop
authors.forename: B
authors.initials: B
authors.lastname: Navarro
authors.forename: E
authors.initials: E
authors.lastname: Fuchs
authors.forename: U
authors.initials: U
authors.lastname: Zechner
authors.forename: T
authors.initials: T
authors.lastname: Haaf
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001483:Base Sequence; D002144:Callithrix; D002540:Cerebral Cortex / Q000378:metabolism; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics*; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D020756:Coatomer Protein / Q000235:genetics*; D019175:DNA Methylation; D017931:DNA Primers / Q000235:genetics; D019143:Evolution, Molecular; D005260:Female; D020022:Genetic Predisposition to Disease; D018392:Genomic Imprinting; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D048529:Papio hamadryas; D011323:Primates / Q000235:genetics*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013045:Species Specificity; D055815:Young Adult
chemical_list: C462511:CEP41 protein, human; C485814:COPG2 protein, human; D020756:Coatomer Protein; D017931:DNA Primers; D011506:Proteins; C103637:mesoderm specific transcript protein