Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons
- Kazuya Iwamoto1,2,7,8,
- Miki Bundo1,2,7,
- Junko Ueda1,
- Michael C. Oldham3,
- Wataru Ukai4,
- Eri Hashimoto4,
- Toshikazu Saito4,
- Daniel H. Geschwind5,6 and
- Tadafumi Kato1,8
- 1Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan;
- 2Department of Molecular Psychiatry, Graduate School of Medicine, The University of Tokyo 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan;
- 3Department of Neurology, The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, California 94143-0525, USA;
- 4Department of Neuropsychiatry, Sapporo Medical University, S.1, W.16, Chuo-ku, Sapporo 060-8543, Japan;
- 5Program in Neurogenetics, Department of Neurology, and the Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA;
- 6Department of Human Genetics, University of California, Los Angeles, California 90095, USA
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↵7 These authors contributed equally to this work.
Abstract
Epigenome information in mammalian brain cells reflects their developmental history, neuronal activity, and environmental exposures. Studying the epigenetic modifications present in neuronal cells is critical to a more complete understanding of the role of the genome in brain functions. We performed comprehensive DNA methylation analysis in neuronal and non-neuronal nuclei obtained from the human prefrontal cortex. Neuronal nuclei manifest qualitatively and quantitatively distinctive DNA methylation patterns, including relative global hypomethylation, differential enrichment of transcription-factor binding sites, and higher methylation of genes expressed in astrocytes. Non-neuronal nuclei showed indistinguishable DNA methylation patterns from bulk cortex and higher methylation of synaptic transmission-related genes compared with neuronal nuclei. We also found higher variation in DNA methylation in neuronal nuclei, suggesting that neuronal cells have more potential ability to change their epigenetic status in response to developmental and environmental conditions compared with non-neuronal cells in the central nervous system.
Footnotes
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↵8 Corresponding authors.
E-mail kaziwamoto-tky{at}umin.ac.jp.
E-mail kato{at}brain.riken.jp.
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[Supplemental material is available for this article. The microarray data from this study have been submitted to the NCBI Gene Expression Omnibus (GEO) (http://www.ncbi.nlm.nih.gov/geo) under accession no. GSE15014.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.112755.110.
- Received July 13, 2010.
- Accepted February 28, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
