Differences in DNA Methylation Patterns and Expression of the CCRK Gene in Human and Nonhuman Primate Cortices
Differences in DNA Methylation Patterns and Expression of the CCRK Gene in Human and Nonhuman Primate Cortices
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DOI：
10.1093/molbev/msp046
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发表时间：
2009-06-01
影响因子：
10.7
通讯作者：
Haaf, Thomas
中科院分区：
文献类型：
--
作者：
Farcas, Ruxandra;Schneider, Eberhard;Haaf, Thomas
胚胎发育和分化过程中DNA甲基化模式的变化与我们基因组的转录可塑性有关。然而，关于DNA甲基化模式的进化保守性以及近缘物种之间表观遗传差异的进化影响，人们知之甚少。在这里，我们比较了人类和黑猩猩七个基因启动子区域的CpG岛(CGI)的甲基化模式。我们在细胞周期相关激酶(CCRK)基因中发现了一个CPGS片段，该片段在成人大脑皮质中的甲基化程度高于在黑猩猩皮质中的甲基化，此外，它在人类和黑猩猩中都表现出相当大的种内变异。物种特异性甲基化区域(SMR)位于CCRK CGI启动子的几乎完全甲基化的5‘区和完全去甲基化的3’区之间。它是Alu-SG1重复序列的一部分，该重复序列已整合到人类和新大陆猴子的共同祖先的启动子区域。这种SMR在恒河猴皮质中相对低甲基化，在狒狒皮质中或多或少完全甲基化，表明灵长类进化过程中异常甲基化动态。在灵长类动物进化过程中，CCRK基因的表达水平也发生了变化。CCRK在人类和恒河猴皮质中的表达水平要高得多，其平均SMR甲基化水平分别为70%和100%，而在黑猩猩和恒河猴皮质中的平均SMR甲基化水平分别为35%和40%。观察到的进化动力学表明，CCRK可能对灵长类大脑的进化起到了重要作用。
Changes in DNA methylation patterns during embryo development and differentiation processes are linked to the transcriptional plasticity of our genome. However, little is known about the evolutionary conservation of DNA methylation patterns and the evolutionary impact of epigenetic differences between closely related species. Here we compared the methylation patterns of CpG islands (CGIs) in the promoter regions of seven genes in humans and chimpanzees. We identified a block of CpGs in the cell cycle-related kinase (CCRK) gene that is more methylated in the adult human cortex than in the chimpanzee cortex and, in addition, it exhibits considerable intraspecific variation both in humans and chimpanzees. The species-specifically methylated region (SMR) lies between the almost completely methylated 5' region and the completely demethylated 3' region of the presumed CCRK CGI promoter. It is part of an Alu-Sg1 repeat that has been integrated into the promoter region in a common ancestor of humans and New World monkeys. This SMR is relatively hypomethylated in the rhesus monkey cortex and more or less completely methylated in the baboon cortex, indicating extraordinary methylation dynamics during primate evolution. The mRNA expression level of CCRK has also changed during the course of primate evolution. CCRK is expressed at much higher levels in human and baboon cortices, which display an average SMR methylation of 70% and 100%, respectively, than in chimpanzee and rhesus macaque cortices with an average SMR methylation of 35% and 40%, respectively. The observed evolutionary dynamics suggests a possibility that CCRK has been important for evolution of the primate brain.