Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex
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Abstract
DNA methylation (DNAm) is a key epigenetic regulator of gene expression across development. The developing prenatal brain is a highly dynamic tissue, but our understanding of key drivers of epigenetic variability across development is limited. We, therefore, assessed genomic methylation at over 39 million sites in the prenatal cortex using whole-genome bisulfite sequencing and found loci and regions in which methylation levels are dynamic across development. We saw that DNAm at these loci was associated with nearby gene expression and enriched for enhancer chromatin states in prenatal brain tissue. Additionally, these loci were enriched for genes associated with neuropsychiatric disorders and genes involved with neurogenesis. We also found autosomal differences in DNAm between the sexes during prenatal development, though these have less clear functional consequences. We lastly confirmed that the dynamic methylation at this critical period is specifically CpG methylation, with generally low levels of CpH methylation. Our findings provide detailed insight into prenatal brain development as well as clues to the pathogenesis of psychiatric traits seen later in life.
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The comparison of our results with sex-specific DNA methylation differences in fetal brain development also showed very little overlap.
“The comparison of our results with sex-specific DNA methylation differences in fetal brain development [88, 89] also showed very little overlap (Additional file 2: Table S19)”
From Sex-specific DNA methylation differences in Alzheimer’s disease pathology (2021) · cites this paper as [89]
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Sex-specific DNA methylation differences in Alzheimer’s disease pathology
Zhang, L., Young, J. I., Gomez, L., Silva, T. C., Schmidt, M. A., Cai, J., Chen, X., Martin, E. R., & Wang, L. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01177-8 · Cited by 58 · see citing works
- Authors
- Perzel Mandell, K. A., Price, A. J., Wilton, R., Collado-Torres, L., Tao, R., Eagles, N. J., Szalay, A. S., Hyde, T. M., Weinberger, D. R., Kleinman, J. E., & Jaffe, A. E.
- Affiliations
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, USA
- Johns Hopkins University (US)
- Lieber Institute for Brain Development (US)
- Corresponding author
- Jaffe, Andrew E.
- ORCID
- Venue
- Epigenetics
- Publisher
- Informa UK Limited
- Published
- 2020-07-15
- Volume
- 16
- Issue
- 1
- Pages
- 1-13
- ISSN
- 1559-2294 (ISSN-L)
- 1559-2308
- PMC
- PMC7889237
- OpenAlex
- W3039187091
- Cited by
- 21
- References
- 10
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 5 · 2020: 3
- FWCI
- 1.38
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by-nd
- Locations
- Epigenetics (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Lieber Institute for Brain Development
- National Institutes of Health
- National Institute of Mental Health (R01MH112751, R21MH102791)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA methylation, fetal brain development, human cortex, epigenetic dynamics, CpG methylation, gene expression, sex differences, neurogenesis, neuropsychiatric disorders, psychiatric traits, whole-genome bisulfite sequencing
- MeSH terms
- Epigenome, Cerebral Cortex, Female, Fetus, Humans, Male, CpG Islands, DNA Methylation, Epigenesis, Genetic, Genetic Loci
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