Developmental regulation and individual differences of neuronal H3K4me3 epigenomes in the prefrontal cortex
Open accessAbstract
Little is known about the regulation of neuronal and other cell-type specific epigenomes from the brain. Here, we map the genome-wide distribution of trimethylated histone H3K4 (H3K4me3), a mark associated with transcriptional regulation, in neuronal and nonneuronal nuclei collected from prefrontal cortex (PFC) of 11 individuals ranging in age from 0.5 to 69 years. Massively parallel sequencing identified 12,732-19,704 H3K4me3 enriched regions (peaks), the majority located proximal to (within 2 kb of) the transcription start site (TSS) of annotated genes. These included peaks shared by neurons in comparison with three control (lymphocyte) cell types, as well as peaks specific to individual subjects. We identified 6,213 genes that show highly enriched H3K4me3 in neurons versus control. At least 1,370 loci, including annotated genes and novel transcripts, were selectively tagged with H3K4me3 in neuronal but not in nonneuronal PFC chromatin. Our results reveal age-correlated neuronal epigenome reorganization, including decreased H3K4me3 at approximately 600 genes (many function in developmental processes) during the first year after birth. In comparison, the epigenome of aging (>60 years) PFC neurons showed less extensive changes, including increased H3K4me3 at 100 genes. These findings demonstrate that H3K4me3 in human PFC is highly regulated in a cell type- and subject-specific manner and highlight the importance of early childhood for developmentally regulated chromatin remodeling in prefrontal neurons.
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Significant remodeling of H3K4me3 occurs during postnatal development and aging of prefrontal neurons.
“A key finding of their study was significant remodeling during postnatal development and aging of prefrontal neurons.”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Cheung et al., 2010
H3K4me3 methylation of NEUROD1 and several members of cadherin and semaphorin families was increased in infants compared to oldest samples (>60 years).
“Notably, H3K4me3 methylation of NEUROD1 and several members of the cadherin and semaphorin families was increased in infants compared to the oldest samples (greater than 60 years of age).”
From The Cellular and Molecular Landscapes of the Developing Human Central Nervous System (2016) · cites this paper as Cheung et al., 2010
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Self-citation
- Authors
- Cheung, I., Shulha, H. P., Jiang, Y., Matevossian, A., Wang, J., Weng, Z., & Akbarian, S.
- Affiliations
- Brudnick Neuropsychiatric Research Institute, Department of Psychiatry,
- Boston University (US)
- Program in Bioinformatics and Integrative Biology, and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2010-04-26
- Volume
- 107
- Issue
- 19
- Pages
- 8824-8829
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2889328
- OpenAlex
- W2154213460
- Cited by
- 235
- References
- 32
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 11 · 2023: 11 · 2022: 7 · 2021: 14 · 2020: 9 · 2019: 11 · 2018: 12 · 2017: 13 · 2016: 22 · 2015: 21 · 2014: 24 · 2013: 24 · 2012: 22
- FWCI
- 8.87
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion)
- Funders
- National Science Foundation
- International Mental Health Research Organization
- National Institute of Mental Health (RC1MH088047, R01MH071476)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- H3K4me3, histone trimethylation, prefrontal cortex, chromatin remodeling, brain development, aging, individual differences, transcription start sites, novel transcripts, human brain
- MeSH terms
- Adolescent, Adult, Aged, Cell Count, Child, Child, Preschool, Histones, Humans, Infant, Lysine, Methylation, Middle Aged, Nerve Tissue Proteins, Neurons, RNA, Messenger, Genome, Prefrontal Cortex, Gene Expression Regulation, Developmental, Gene Expression Profiling, Antigens, Nuclear, Chromatin Assembly and Disassembly, Epigenesis, Genetic, Young Adult
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