Cited by 369Epigenetics and DNA MethylationGenomics and Chromatin DynamicsGenetic Syndromes and Imprinting

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DNA Methylation Signatures in Development and Aging of the Human Prefrontal Cortex

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Numata, Shusuke, Ye, Tianzhang, Hyde, Thomas M., Guitart-Navarro, Xavier, Tao, Ran, Wininger, Michael, Colantuoni, Carlo, Weinberger, Daniel R., Kleinman, Joel E., Lipska, Barbara K.·2012·The American Journal of Human Genetics

DOI 10.1016/j.ajhg.2011.12.020PMC PMC3276664

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Abstract

The human prefrontal cortex (PFC), a mastermind of the brain, is one of the last brain regions to mature. To investigate the role of epigenetics in the development of PFC, we examined DNA methylation in ∼14,500 genes at ∼27,000 CpG loci focused on 5' promoter regions in 108 subjects range in age from fetal to elderly. DNA methylation in the PFC shows unique temporal patterns across life. The fastest changes occur during the prenatal period, slow down markedly after birth and continue to slow further with aging. At the genome level, the transition from fetal to postnatal life is typified by a reversal of direction, from demethylation prenatally to increased methylation postnatally. DNA methylation is strongly associated with genotypic variants and correlates with expression of a subset of genes, including genes involved in brain development and in de novo DNA methylation. Our results indicate that promoter DNA methylation in the human PFC is a highly dynamic process modified by genetic variance and regulating gene transcription. Additional discovery is made possible with a stand-alone application, BrainCloudMethyl.

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Authors: Numata, S., Ye, T., Hyde, T. M., Guitart-Navarro, X., Tao, R., Wininger, M., Colantuoni, C., Weinberger, D. R., Kleinman, J. E., & Lipska, B. K.
Affiliations: National Institutes of Health (US)
Corresponding author: Lipska, Barbara K.
ORCID: Numata, Shusuke
Tao, Ran
Wininger, Michael
Colantuoni, Carlo
Weinberger, Daniel R.
Kleinman, Joel E.
Venue: The American Journal of Human Genetics
Publisher: Elsevier BV
Published: 2012-02
Volume: 90
Issue: 2
Pages: 260-272
ISSN: 0002-9297 (ISSN-L)
DOI: 10.1016/j.ajhg.2011.12.020
PMC: PMC3276664
OpenAlex: W1994872818
Cited by: 364
References: 54
Citations by year: 2026: 1 · 2025: 9 · 2024: 13 · 2023: 11 · 2022: 25 · 2021: 24 · 2020: 21 · 2019: 21 · 2018: 28 · 2017: 29 · 2016: 44 · 2015: 36 · 2014: 34 · 2013: 46 · 2012: 22
FWCI: 17.75
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 568 d)
Locations: The American Journal of Human Genetics (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Mental Health
National Human Genome Research 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, prefrontal cortex, brain development, brain aging, promoter methylation, CpG sites, genetic variants, gene expression regulation, de novo methylation
MeSH terms: Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Aging, Child, Child, Preschool, Female, Fetus, Humans, Infant, Infant, Newborn, Male, Middle Aged, Promoter Regions, Genetic, Sex Factors, Genetic Variation, Prefrontal Cortex, CpG Islands, DNA Methylation, Quantitative Trait Loci, Epigenesis, Genetic, Young Adult

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DNA Methylation Signatures in Development and Aging of the Human Prefrontal Cortex

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