Clinical Brain Disorders Branch, Genes, Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892, USA.
Am J Hum Genet. 2012 Feb 10;90(2):260-72. doi: 10.1016/j.ajhg.2011.12.020. Epub 2012 Feb 2.
The human prefrontal cortex (PFC), a mastermind of the brain, is one of the last brain regions to mature. To investigate the role of epigenetics in the development of PFC, we examined DNA methylation in ∼14,500 genes at ∼27,000 CpG loci focused on 5' promoter regions in 108 subjects range in age from fetal to elderly. DNA methylation in the PFC shows unique temporal patterns across life. The fastest changes occur during the prenatal period, slow down markedly after birth and continue to slow further with aging. At the genome level, the transition from fetal to postnatal life is typified by a reversal of direction, from demethylation prenatally to increased methylation postnatally. DNA methylation is strongly associated with genotypic variants and correlates with expression of a subset of genes, including genes involved in brain development and in de novo DNA methylation. Our results indicate that promoter DNA methylation in the human PFC is a highly dynamic process modified by genetic variance and regulating gene transcription. Additional discovery is made possible with a stand-alone application, BrainCloudMethyl.
人类前额叶皮层（PFC）是大脑的“总指挥”，也是最后发育成熟的大脑区域之一。为了研究表观遗传学在 PFC 发育中的作用，我们在 108 名年龄从胎儿到老年的研究对象中，针对 5'启动子区域内的约 14500 个基因、约 27000 个 CpG 位点，检测了 DNA 甲基化。在整个生命过程中，PFC 的 DNA 甲基化呈现出独特的时间模式。最快的变化发生在产前阶段，出生后明显减慢，并随着年龄的增长进一步减慢。从基因组水平上看，从胎儿期到出生后的转变以方向的逆转为特征，即从产前去甲基化到出生后甲基化增加。DNA 甲基化与基因型变异强烈相关，并与一部分基因的表达相关，包括参与大脑发育和从头 DNA 甲基化的基因。我们的研究结果表明，人类 PFC 启动子 DNA 甲基化是一个高度动态的过程，受遗传变异的修饰，并调节基因转录。通过 BrainCloudMethyl 这一独立应用，还可以进一步发现。
