Neurons show distinctive DNA methylation profile and higher interindividual variations compared with non-neurons
Open accessAbstract
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.
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Distinctive DNA methylation patterns between neuronal and glial cells have been observed, and variation in DNA methylation appears to be higher in neuronal cells in response to the environment.
“distinctive DNA methylation patterns between neuronal and glial cells have been observed, and variation in DNA methylation appears to be higher in neuronal cells in response to the environment (Iwamoto et al., 2011).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Iwamoto et al., 2011
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Cites
DNA methylation patterns and epigenetic memory
Bird, A. (2002) · Genes & Development · doi:10.1101/gad.947102 · Cited by 7,124 · see citing works
Epigenetic programming by maternal behavior
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., & Meaney, M. J. (2004) · Nature Neuroscience · doi:10.1038/nn1276 · Cited by 6,177 · see citing works
Conversion of 5-Methylcytosine to 5-Hydroxymethylcytosine in Mammalian DNA by MLL Partner TET1
Tahiliani, M., Koh, K. P., Shen, Y., Pastor, W. A., Bandukwala, H., Brudno, Y., Agarwal, S., Iyer, L. M., Liu, D. R., Aravind, L., et al. (2009) · Science · doi:10.1126/science.1170116 · Cited by 5,836 · see citing works
PANTHER: A Library of Protein Families and Subfamilies Indexed by FunctionPreprint
Thomas, P. D., Campbell, M. J., Kejariwal, A., Mi, H., Karlak, B., Daverman, R., Diemer, K., Muruganujan, A., & Narechania, A. (2003) · Genome Research · doi:10.1101/gr.772403 · Cited by 2,912 · see citing works
MethPrimer: designing primers for methylation PCRs
Li, L.-C., & Dahiya, R. (2002) · Bioinformatics · doi:10.1093/bioinformatics/18.11.1427 · Cited by 2,741 · see citing works
The Nuclear DNA Base 5-Hydroxymethylcytosine Is Present in Purkinje Neurons and the Brain
Kriaucionis, S., & Heintz, N. (2009) · Science · doi:10.1126/science.1169786 · Cited by 2,700 · see citing works
NeuN, a neuronal specific nuclear protein in vertebratesxs
Mullen, R. J., Buck, C. R., & Smith, A. M. (1992) · Development · doi:10.1242/dev.116.1.201 · Cited by 2,351 · see citing works
MatInspector and beyond: promoter analysis based on transcription factor binding sites
Cartharius, K., Frech, K., Grote, K., Klocke, B., Haltmeier, M., Klingenhoff, A., Frisch, M., Bayerlein, M., & Werner, T. (2005) · Computer applications in the biosciences · doi:10.1093/bioinformatics/bti473 · Cited by 1,962 · see citing works
Phenotypic plasticity and the epigenetics of human disease
Feinberg, A. P. (2007) · Nature · doi:10.1038/nature05919 · Cited by 1,613 · see citing works
DNA Methylation-Related Chromatin Remodeling in Activity-Dependent <i>Bdnf</i> Gene Regulation
Martinowich, K., Hattori, D., Wu, H., Fouse, S., He, F., Hu, Y., Fan, G., & Sun, Y. E. (2003) · Science · doi:10.1126/science.1090842 · Cited by 1,405 · see citing works
Epigenetic regulation in psychiatric disorders
Tsankova, N., Renthal, W., Kumar, A., & Nestler, E. J. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2132 · Cited by 1,400 · see citing works
The Story of Rett Syndrome: From Clinic to Neurobiology
Chahrour, M., & Zoghbi, H. Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.001 · Cited by 1,265 · see citing works
Derepression of BDNF Transcription Involves Calcium-Dependent Phosphorylation of MeCP2
Chen, W. G., Chang, Q., Lin, Y., Meissner, A., West, A. E., Griffith, E. C., Jaenisch, R., & Greenberg, M. E. (2003) · Science · doi:10.1126/science.1086446 · Cited by 1,232 · see citing works
Covalent Modification of DNA Regulates Memory Formation
Miller, C. A., & Sweatt, J. D. (2007) · Neuron · doi:10.1016/j.neuron.2007.02.022 · Cited by 1,180 · see citing works
A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements
Yang, A. S. (2004) · Nucleic Acids Research · doi:10.1093/nar/gnh032 · Cited by 1,033 · see citing works
Dnmt1 and Dnmt3a maintain DNA methylation and regulate synaptic function in adult forebrain neurons
Feng, J., Zhou, Y., Campbell, S. L., Le, T., Li, E., Sweatt, J. D., Silva, A. J., & Fan, G. (2010) · Nature Neuroscience · doi:10.1038/nn.2514 · Cited by 1,019 · see citing works
L1 retrotransposition in human neural progenitor cells
Coufal, N. G., Garcia-Perez, J. L., Peng, G. E., Yeo, G. W., Mu, Y., Lovci, M. T., Morell, M., O’Shea, K. S., Moran, J. V., & Gage, F. H. (2009) · Nature · doi:10.1038/nature08248 · Cited by 814 · see citing works
Epigenomic Profiling Reveals DNA-Methylation Changes Associated with Major Psychosis
Mill, J., Tang, T., Kaminsky, Z., Khare, T., Yazdanpanah, S., Bouchard, L., Jia, P., Assadzadeh, A., Flanagan, J., Schumacher, A., et al. (2008) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2008.01.008 · Cited by 773 · see citing works
Functional organization of the transcriptome in human brain
Oldham, M. C., Konopka, G., Iwamoto, K., Langfelder, P., Kato, T., Horvath, S., & Geschwind, D. H. (2008) · Nature Neuroscience · doi:10.1038/nn.2207 · Cited by 752 · cited 3× · see citing works
“Average correlation between each module eigengene (Oldham et al. 2008) and the expression levels of genes associated with neuronal MR (NeuN+), non-neuronal MR (NeuN ), and all brain-expressed genes (all probes).”
BackgroundInfluentialSelf-citationEssential Role of the Histone Methyltransferase G9a in Cocaine-Induced Plasticity
Maze, I., Covington, H. E., Dietz, D. M., LaPlant, Q., Renthal, W., Russo, S. J., Mechanic, M., Mouzon, E., Neve, R. L., Haggarty, S. J., et al. (2010) · Science · doi:10.1126/science.1179438 · Cited by 665 · see citing works
Maternal care as a model for experience-dependent chromatin plasticity?
Meaney, M. J., & Szyf, M. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.07.006 · Cited by 658 · see citing works
High-throughput DNA methylation profiling using universal bead arraysPreprint
Bibikova, M. V., Lin, Z., Zhou, L., Chudin, E., Wickham‐Garcia, E., Wu, B., Doucet, D., Thomas, N. J., Wang, Y., Vollmer, E., et al. (2006) · Genome Research · doi:10.1101/gr.4410706 · Cited by 657 · see citing works
Retrospective Birth Dating of Cells in Humans
Spalding, K. L., Bhardwaj, R. D., Buchholz, B. A., Druid, H., & Frisén, J. (2005) · Cell · doi:10.1016/j.cell.2005.04.028 · Cited by 626 · see citing works
Evidence That DNA (Cytosine-5) Methyltransferase Regulates Synaptic Plasticity in the Hippocampus
Levenson, J. M., Roth, T. L., Lubin, F. D., Miller, C. A., Huang, I.-C., Desai, P., Malone, L. M., & Sweatt, J. D. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m511767200 · Cited by 615 · see citing works
Takizawa, T., Nakashima, K., Namihira, M., Ochiai, W., Uemura, A., Yanagisawa, M., Fujita, N., Nakao, M., & Taga, T. (2001) · Developmental Cell · doi:10.1016/s1534-5807(01)00101-0 · Cited by 608 · see citing works
QUMA: quantification tool for methylation analysis
Kumaki, Y., Oda, M., & Okano, M. (2008) · Nucleic Acids Research · doi:10.1093/nar/gkn294 · Cited by 606 · see citing works
Decoding the Epigenetic Language of Neuronal Plasticity
Borrelli, E., Nestler, E. J., Allis, C. D., & Sassone‐Corsi, P. (2008) · Neuron · doi:10.1016/j.neuron.2008.10.012 · Cited by 529 · see citing works
Kim, E., Naisbitt, S., Hsueh, Y.-P., Rao, A., Rothschild, A., Craig, A. M., & Sheng, M. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.136.3.669 · Cited by 516 · see citing works
Iwamoto, K., Bundo, M., & Kato, T. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddi022 · Cited by 496 · see citing works
Self-citationJin, S.-G., Kadam, S., & Pfeifer, G. P. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq223 · Cited by 437 · see citing works
Model-based analysis of tiling-arrays for ChIP-chip
Johnson, W. E., Li, W., Meyer, C. A., Gottardo, R., Carroll, J. S., Brown, M. A., & Liu, X. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601180103 · Cited by 428 · see citing works
Siegmund, K. D., Connor, C., Campan, M., Long, T. I., Weisenberger, D. J., Biniszkiewicz, D., Jaenisch, R., Laird, P. W., & Akbarian, S. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000895 · Cited by 411 · see citing works
Peles, E., Nativ, M., Lustig, M., Grumet, M., Schilling, J., Martinez, R., Plowman, G. D., & Schlessinger, J. (1997) · The EMBO Journal · doi:10.1093/emboj/16.5.978 · Cited by 400 · cited 1× · see citing works
“CNTNAP1 encodes an axonal protein important for cell–cell communication between neurons and glias (Peles et al. 1997).”
BackgroundIncreased BDNF Promoter Methylation in the Wernicke Area of Suicide Subjects
Keller, S., Sarchiapone, M., Zarrilli, F., Videtič, A., Ferraro, A., Carli, V., Sacchetti, S., Lembo, F., Angiolillo, A., Jovanovic, N., et al. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.9 · Cited by 379 · see citing works
Zhao, X., Ueba, T., Christie, B. R., Barkho, B. Z., McConnell, M. J., Nakashima, K., Lein, E. S., Eadie, B. D., Willhoite, A. R., Muotri, A. R., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1131928100 · Cited by 376 · see citing works
Genomic imprinting effects on brain development and function
Wilkinson, L. S., Davies, W., & Isles, A. R. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2235 · Cited by 373 · see citing works
Constitutional Aneuploidy in the Normal Human Brain
Rehen, S. K., Yung, Y. C., McCreight, M. P., Kaushal, D., Yang, A. H., Almeida, B. S. V., Kingsbury, M. A., Cabral, K. M. D. S., McConnell, M. J., Anliker, B., et al. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.4560-04.2005 · Cited by 320 · see citing works
Rauch, T. A., Li, H., Wu, X., & Pfeifer, G. P. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1888 · Cited by 292 · see citing works
DNA Methylation Signatures within the Human Brain
Ladd‐Acosta, C., Pevsner, J., Sabunciyan, S., Yolken, R. H., Webster, M. J., Dinkins, T., Callinan, P. A., Fan, J., Potash, J. B., & Feinberg, A. P. (2007) · The American Journal of Human Genetics · doi:10.1086/524110 · Cited by 277 · see citing works
Generation of neuronal variability and complexity
Muotri, A. R., & Gage, F. H. (2006) · Nature · doi:10.1038/nature04959 · Cited by 271 · see citing works
Nelson, E. D., Kavalali, E. T., & Monteggia, L. M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3796-07.2008 · Cited by 254 · see citing works
Iwamoto, K., Bundo, M., Yamada, K., Takao, H., Iwayama‐Shigeno, Y., Yoshikawa, T., & Kato, T. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.0766-05.2005 · Cited by 243 · see citing works
Self-citationCheung, I., Shulha, H. P., Jiang, Y., Matevossian, A., Wang, J., Weng, Z., & Akbarian, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1001702107 · Cited by 235 · see citing works
Epigenetics in the Nervous System: Figure 1.
Jiang, Y., Langley, B. C., Lubin, F. D., Renthal, W. R., Wood, M. A., Yasui, D. H., Kumar, A., Nestler, E. J., Akbarian, S., & Beckel-Mitchener, A. C. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.3797-08.2008 · Cited by 214 · see citing works
Using LUMA: a Luminometric-Based Assay for Global DNA-Methylation
Mohsen, K., Johansson, S., & Ekström, T. J. (2006) · Epigenetics · doi:10.4161/epi.1.1.2587 · Cited by 168 · see citing works
Methylation Status of the Reelin Promoter Region in the Brain of Schizophrenic Patients
Tochigi, M., Iwamoto, K., Bundo, M., Komori, A., Sasaki, T., Kato, N., & Kato, T. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.07.003 · Cited by 134 · see citing works
Self-citationBrown, S. E., Weaver, I. C. G., Meaney, M. J., & Moshe Szyf, A. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.05.028 · Cited by 77 · see citing works
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Labonte, B., Yerko, V., Gross, J., Mechawar, N., Meaney, M. J., Szyf, M., & Turecki, G. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.01.034 · Cited by 345 · see citing works
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- Authors
- Iwamoto, K., Bundo, M., Ueda, J., Oldham, M. C., Ukai, W., Hashimoto, E., Saito, T., Geschwind, D. H., & Kato, T.
- Affiliations
- RIKEN Center for Brain Science (JP)
- University of California, San Francisco (US)
- Sapporo Medical University (JP)
- University of California, Los Angeles (US)
- ORCID
- Venue
- Genome Research
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2011-04-05
- Volume
- 21
- Issue
- 5
- Pages
- 688-696
- ISSN
- 1088-9051 (ISSN-L)
- PMC
- PMC3083085
- OpenAlex
- W2102953188
- Cited by
- 189
- References
- 47
- Citations by year
- 2026: 3 · 2025: 1 · 2024: 8 · 2023: 10 · 2022: 7 · 2021: 7 · 2020: 12 · 2019: 7 · 2018: 15 · 2017: 17 · 2016: 15 · 2015: 24 · 2014: 22 · 2013: 21 · 2012: 20
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genome Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (21390334, 23591679, 23591677)
- RIKEN
- National Institute of Mental Health (R37MH060233)
- RIKEN Brain Science Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- DNA methylation, neurons, prefrontal cortex, NeuN, interindividual variability, global hypomethylation, transcription factor binding sites
- MeSH terms
- Animals, Astrocytes, Cell Nucleus, Cerebellum, Cerebral Cortex, Humans, Male, Neurons, Promoter Regions, Genetic, Proteins, Genetic Variation, Gene Expression Regulation, Developmental, DNA Methylation, Oligonucleotide Array Sequence Analysis, Epigenesis, Genetic, Epigenomics
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