The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
DNA Methylation in the Human Cerebral Cortex Is Dynamically Regulated throughout the Life Span and Involves Differentiated Neurons
Open accessAbstract
The role of DNA cytosine methylation, an epigenetic regulator of chromatin structure and function, during normal and pathological brain development and aging remains unclear. Here, we examined by MethyLight PCR the DNA methylation status at 50 loci, encompassing primarily 5' CpG islands of genes related to CNS growth and development, in temporal neocortex of 125 subjects ranging in age from 17 weeks of gestation to 104 years old. Two psychiatric disease cohorts--defined by chronic neurodegeneration (Alzheimer's) or lack thereof (schizophrenia)--were included. A robust and progressive rise in DNA methylation levels across the lifespan was observed for 8/50 loci (GABRA2, GAD1, HOXA1, NEUROD1, NEUROD2, PGR, STK11, SYK) typically in conjunction with declining levels of the corresponding mRNAs. Another 16 loci were defined by a sharp rise in DNA methylation levels within the first few months or years after birth. Disease-associated changes were limited to 2/50 loci in the Alzheimer's cohort, which appeared to reflect an acceleration of the age-related change in normal brain. Additionally, methylation studies on sorted nuclei provided evidence for bidirectional methylation events in cortical neurons during the transition from childhood to advanced age, as reflected by significant increases at 3, and a decrease at 1 of 10 loci. Furthermore, the DNMT3a de novo DNA methyl-transferase was expressed across all ages, including a subset of neurons residing in layers III and V of the mature cortex. Therefore, DNA methylation is dynamically regulated in the human cerebral cortex throughout the lifespan, involves differentiated neurons, and affects a substantial portion of genes predominantly by an age-related increase.
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Cites
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“Epigenetic modification of chromatin, including DNA methylation at the sites of CpG dinucleotides, is a key regulator of gene expression, growth and differentiation in virtually all tissues, including brain [1,2,3,4].”
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Cited by
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
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DNA methylation landscapes: Provocative insights from epigenomics
Suzuki, M. M., & Bird, A. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2341 · Cited by 3,039
Global epigenomic reconfiguration during mammalian brain development
Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., Lucero, J., Huang, Y., Dwork, A. J., Schultz, M. D., et al. (2013) · Science · doi:10.1126/science.1237905 · Cited by 1,830
Lasting epigenetic influence of early-life adversity on the BDNF gene
Roth, T. L., Lubin, F. D., Funk, A. J., & Sweatt, J. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.028 · Cited by 1,273
Christensen, B. C., Houseman, E. A., Marsit, C. J., Zheng, S., Wrensch, M. R., Wiemels, J. L., Nelson, H. H., Karagas, M. R., Padbury, J. F., Bueno, R., et al. (2009) · PLoS Genetics · doi:10.1371/journal.pgen.1000602 · Cited by 1,075
Metadata
- Authors
- Siegmund, K. D., Connor, C. M., Campan, M., Long, T. I., Weisenberger, D. J., Biniszkiewicz, D., Jaenisch, R., Laird, P. W., & Akbarian, S.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2007-09-19
- Volume
- 2
- Issue
- 9
- Pages
- e895
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2053901332
- Cited by
- 414
- References
- 58
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- gold
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- Siegmund, K. D., Connor, C. M., Campan, M., Long, T. I., Weisenberger, D. J., Biniszkiewicz, D., Jaenisch, R., Laird, P. W., & Akbarian, S. (2007). DNA Methylation in the Human Cerebral Cortex Is Dynamically Regulated throughout the Life Span and Involves Differentiated Neurons. PLoS ONE. https://doi.org/10.1371/journal.pone.0000895
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