哺乳动物大脑发育过程中的全基因组表观遗传重编程。
Global epigenomic reconfiguration during mammalian brain development.
机构信息
Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Plant Energy Biology [Australian Research Council Center of Excellence (CoE)] and Computational Systems Biology (Western Australia CoE), School of Chemistry and Biochemistry, The University of Western Australia, Perth, WA 6009, Australia.
出版信息
Science. 2013 Aug 9;341(6146):1237905. doi: 10.1126/science.1237905. Epub 2013 Jul 4.
DNA methylation is implicated in mammalian brain development and plasticity underlying learning and memory. We report the genome-wide composition, patterning, cell specificity, and dynamics of DNA methylation at single-base resolution in human and mouse frontal cortex throughout their lifespan. Widespread methylome reconfiguration occurs during fetal to young adult development, coincident with synaptogenesis. During this period, highly conserved non-CG methylation (mCH) accumulates in neurons, but not glia, to become the dominant form of methylation in the human neuronal genome. Moreover, we found an mCH signature that identifies genes escaping X-chromosome inactivation. Last, whole-genome single-base resolution 5-hydroxymethylcytosine (hmC) maps revealed that hmC marks fetal brain cell genomes at putative regulatory regions that are CG-demethylated and activated in the adult brain and that CG demethylation at these hmC-poised loci depends on Tet2 activity.
DNA 甲基化参与哺乳动物大脑发育和学习记忆相关的可塑性。我们在单碱基分辨率水平上报告了人类和小鼠大脑前额叶皮质在整个生命周期中的 DNA 甲基化的全基因组组成、模式、细胞特异性和动态变化。广泛的甲基组构重排发生在胎儿到成年早期的发育过程中，与突触发生相吻合。在此期间，高度保守的非 CG 甲基化（mCH）在神经元中积累，但不在神经胶质细胞中积累，成为人类神经元基因组中主要的甲基化形式。此外，我们发现了一个 mCH 特征，可以识别逃避 X 染色体失活的基因。最后，全基因组单碱基分辨率 5-羟甲基胞嘧啶（hmC）图谱显示，hmC 标记胎儿大脑细胞基因组中潜在的调控区域，这些区域在成年大脑中 CG 去甲基化并被激活，并且这些 hmC 倾向的位点的 CG 去甲基化依赖于 Tet2 活性。
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