Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain.

Autor: Guo JU; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [3] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [4] [5]., Su Y; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [3]., Shin JH; Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Shin J; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Li H; Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., Xie B; Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Zhong C; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Hu S; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Le T; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA., Fan G; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA., Zhu H; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Chang Q; Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA., Gao Y; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] Lieber Institute for Brain Development, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Ming GL; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [3] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [4] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA., Song H; 1] Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [2] The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [3] Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. [4] Graduate Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2014 Feb; Vol. 17 (2), pp. 215-22. Date of Electronic Publication: 2013 Dec 22.
DOI: 10.1038/nn.3607
Abstrakt: DNA methylation has critical roles in the nervous system and has been traditionally considered to be restricted to CpG dinucleotides in metazoan genomes. Here we show that the single base-resolution DNA methylome from adult mouse dentate neurons consists of both CpG (~75%) and CpH (~25%) methylation (H = A/C/T). Neuronal CpH methylation is conserved in human brains, enriched in regions of low CpG density, depleted at protein-DNA interaction sites and anticorrelated with gene expression. Functionally, both methylated CpGs (mCpGs) and mCpHs can repress transcription in vitro and are recognized by methyl-CpG binding protein 2 (MeCP2) in neurons in vivo. Unlike most CpG methylation, CpH methylation is established de novo during neuronal maturation and requires DNA methyltransferase 3A (DNMT3A) for active maintenance in postmitotic neurons. These characteristics of CpH methylation suggest that a substantially expanded proportion of the neuronal genome is under cytosine methylation regulation and provide a new foundation for understanding the role of this key epigenetic modification in the nervous system.
Databáze: MEDLINE