Kinde Benyam, Gabel Harrison W, Gilbert Caitlin S, Griffith Eric C, Greenberg Michael E
Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
Department of Neurobiology, Harvard Medical School, Boston, MA 02115
Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):6800-6. doi: 10.1073/pnas.1411269112. Epub 2015 Mar 4.
DNA methylation at CpG dinucleotides is an important epigenetic regulator common to virtually all mammalian cell types, but recent evidence indicates that during early postnatal development neuronal genomes also accumulate uniquely high levels of two alternative forms of methylation, non-CpG methylation and hydroxymethylation. Here we discuss the distinct landscape of DNA methylation in neurons, how it is established, and how it might affect the binding and function of protein readers of DNA methylation. We review studies of one critical reader of DNA methylation in the brain, the Rett syndrome protein methyl CpG-binding protein 2 (MeCP2), and discuss how differential binding affinity of MeCP2 for non-CpG and hydroxymethylation may affect the function of this methyl-binding protein in the nervous system.
CpG二核苷酸处的DNA甲基化是几乎所有哺乳动物细胞类型共有的一种重要表观遗传调节因子，但最近的证据表明，在出生后早期发育过程中，神经元基因组还积累了两种独特的高水平替代甲基化形式，即非CpG甲基化和羟甲基化。在这里，我们讨论神经元中DNA甲基化的独特格局、其建立方式以及它可能如何影响DNA甲基化蛋白识别器的结合和功能。我们回顾了对大脑中一种关键的DNA甲基化识别器——雷特综合征蛋白甲基CpG结合蛋白2（MeCP2）的研究，并讨论了MeCP2对非CpG和羟甲基化的不同结合亲和力可能如何影响这种甲基结合蛋白在神经系统中的功能。
