DNA methylation signatures in development and aging of the human prefrontal cortex
Open accessAbstract
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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At loci that changed both in fetal and postnatal periods, demethylated states predominated during fetal periods with increasing methylation observed during postnatal period.
“Moreover, at loci that changed both in fetal and postnatal periods, demethylated states predominated during fetal periods with increasing methylation observed during the postnatal period.”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Numata et al., 2012
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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
- 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)
- 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
- 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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