Schneider E, Mayer S, El Hajj N, Jensen L R, Kuss A W, Zischler H, Kondova I, Bontrop R E, Navarro B, Fuchs E, Zechner U, Haaf T
Institute of Human Genetics, Julius Maximilians University, Würzburg, Germany.
Cytogenet Genome Res. 2012;136(4):278-87. doi: 10.1159/000337298. Epub 2012 Mar 24.
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.
人类7号染色体q32区域的自闭症易感位点包含母源印记的MEST基因以及非印记的COPG2和TSGA14基因。自闭症是一种“社会脑”疾病，有人提出这是由于父源表达基因失衡所致。为了研究类人猿灵长类动物进化过程中7q32位点的调控情况，我们分析了人类、黑猩猩、旧世界猴（狒狒和恒河猴）以及新世界猴（狨猴）大脑皮质中MEST、COPG2和TSGA14的甲基化和表达模式。在所有人类和类人猿灵长类动物的大脑皮质中，MEST启动子呈半甲基化状态，这符合差异甲基化印记控制区域的预期，而COPG2和TSGA14启动子则完全去甲基化，这是转录活跃的非印记基因的典型特征。MEST基因在所有分析物种中的mRNA表达水平也相当。相比之下，与黑猩猩、旧世界猴和新世界猴相比，人类大脑皮质中COPG2的表达下调。与黑猩猩和狨猴相比，TSGA14在人类大脑中要么没有差异调控，要么与狒狒相比有轻微上调。人类特有的下调现象支持了COPG2在“社会脑”发育中的作用。启动子甲基化模式在进化过程中似乎比基因表达模式更稳定，这表明其他机制可能对灵长类动物之间的基因表达差异更为重要。
