TY - JOUR
T1 - DNA methylation signatures in development and aging of the human prefrontal cortex
AU - Numata, Shusuke
AU - Ye, Tianzhang
AU - Hyde, Thomas M.
AU - Guitart-Navarro, Xavier
AU - Tao, Ran
AU - Wininger, Michael
AU - Colantuoni, Carlo
AU - Weinberger, Daniel R.
AU - Kleinman, Joel E.
AU - Lipska, Barbara K.
N1 - Funding Information:
We thank Liqin Wang and Vesna Imamovic for their technical expertise; Mary Herman for her contribution to the Clinical Brain Disorders Branch/National Institute of Mental Health brain collection; Abdel Elkahloun at National Human Genome Research Institute Microarray Core Facility for scanning data; and Ronald Zielke, Robert Johnson, and Robert Vigorito at the NICHD Brain and Tissue Bank for Developmental Disorders, University of Maryland School of Medicine, for their collection of brains. We also thank the families of the deceased for the donations of brain tissue and their time and effort devoted to the consent process and interviews. This research was supported by the Intramural Research Program of the National Institute of Mental Health at the National Institutes of Health.
PY - 2012/2/10
Y1 - 2012/2/10
N2 - 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.
AB - 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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U2 - 10.1016/j.ajhg.2011.12.020
DO - 10.1016/j.ajhg.2011.12.020
M3 - Article
C2 - 22305529
AN - SCOPUS:84857062545
SN - 0002-9297
VL - 90
SP - 260
EP - 272
JO - American journal of human genetics
JF - American journal of human genetics
IS - 2
ER -