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Neuroscience. 2014 May 30;268:139-48. doi: 10.1016/j.neuroscience.2014.03.021. Epub 2014 Mar 19.

Hydroxymethylation and DNA methylation profiles in the prefrontal cortex of the non-human primate rhesus macaque and the impact of maternal deprivation on hydroxymethylation.

Author information

1
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada.
2
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada; Sackler Program for Epigenetics & Developmental Psychobiology, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada; Research Unit on Children's Psycho-Social Maladjustment and St-Justine Hospital Research Centre, University of Montreal, Montreal, Quebec H3T 1C5, Canada.
3
Laboratory of Comparative Ethology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-7971, USA; Psychology Department & Harlow Center for Biological Psychology, University of Wisconsin, Madison, WI 53715-2613, USA.
4
Laboratory of Comparative Ethology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-7971, USA. Electronic address: suomis@lce.nichd.nih.gov.
5
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada; Sackler Program for Epigenetics & Developmental Psychobiology, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec H3G 1Y6, Canada. Electronic address: moshe.szyf@mcgill.ca.

Abstract

5-Hydroxymethylcytosine (5hmC) is abundant in the brain, suggesting an important role in epigenetic control of neuronal functions. In this paper, we show that 5hmC and 5-methylcytosine (5mC) levels are coordinately distributed in gene promoters of the rhesus macaque prefrontal cortex. Although promoter hydroxymethylation and methylation are overall negatively correlated with expression, a subset of highly expressed genes involved in specific cerebral functions is associated with high levels of 5mC and 5hmC. These relationships were also observed in the mouse cortex. Furthermore, we found that early-life maternal deprivation is associated, in the adult monkey cortex, with DNA hydroxymethylation changes of promoters of genes related to neurological functions and psychological disorders. These results reveal that early social adversity triggers variations in brain DNA hydroxymethylation that could be detected in adulthood.

KEYWORDS:

brain; early-adversity; hydroxymethylation; maternal deprivation; monkeys; rearing

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