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Early life adversity alters normal sex-dependent developmental dynamics of DNA methylation

Published online by Cambridge University Press:  30 September 2016

Renaud Massart ,
Zsofia Nemoda ,
Matthew J. Suderman ,
Sheila Sutti ,
Angela M. Ruggiero ,
Amanda M. Dettmer ,
Stephen J. Suomi  and
Moshe Szyf
Renaud Massart
Affiliation:
McGill University
Zsofia Nemoda
Affiliation:
McGill University
Matthew J. Suderman
Affiliation:
McGill University
Sheila Sutti
Affiliation:
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Angela M. Ruggiero
Affiliation:
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Amanda M. Dettmer
Affiliation:
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Stephen J. Suomi*
Affiliation:
Eunice Kennedy Shriver National Institute of Child Health and Human Development
Moshe Szyf*
Affiliation:
McGill University
*
Address correspondence and reprint requests to: Stephen J. Suomi, Laboratory of Comparative Ethology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-7971; E-mail: [email protected]; or Moshe Szyf, Department of Pharmacology and Therapeutics, McGill University, 3655 Promonade Sir William Osler, Montreal, QC H3G Y6, Canada; E-mail: [email protected].
Address correspondence and reprint requests to: Stephen J. Suomi, Laboratory of Comparative Ethology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-7971; E-mail: [email protected]; or Moshe Szyf, Department of Pharmacology and Therapeutics, McGill University, 3655 Promonade Sir William Osler, Montreal, QC H3G Y6, Canada; E-mail: [email protected].
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Abstract

Studies in rodents, nonhuman primates, and humans suggest that epigenetic processes mediate between early life experiences and adult phenotype. However, the normal evolution of epigenetic programs during child development, the effect of sex, and the impact of early life adversity on these trajectories are not well understood. This study mapped the genome-wide DNA methylation changes in CD3+ T lymphocytes from rhesus monkeys from postnatal day 14 through 2 years of age in both males and females and determined the impact of maternal deprivation on the DNA methylation profile. We show here that DNA methylation profiles evolve from birth to adolescence and are sex dependent. DNA methylation changes accompany imposed weaning, attenuating the difference between males and females. Maternal separation at birth alters the normal evolution of DNA methylation profiles and targets genes that are also affected by a later stage maternal separation, that is, weaning. Our results suggest that early life events dynamically interfere with the normal developmental evolution of the DNA methylation profile and that these changes are highly effected by sex.

Type
Special Section Articles
Information
Development and Psychopathology , Volume 28 , Special Issue 4pt2: Epigenetics: Development, Psychopathology, Resilience, and Preventive Intervention , November 2016 , pp. 1259 - 1272
Copyright
Copyright © Cambridge University Press 2016 

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References

Barr, C. S., Newman, T. K., Becker, M. L., Parker, C. C., Champoux, M., Lesch, K. P., et al. (2003). The utility of the non-human primate; model for studying gene by environment interactions in behavioral research. Genes Brain Behavior, 2, 336–340.Google Scholar
Bartel, D. P. (2004). MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell, 116, 281–297.Google Scholar
Bolstad, B. M., Irizarry, R. A., Astrand, M., & Speed, T. P. (2003). A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics, 19, 185–193.Google Scholar
Cao-Lei, L., Dancause, K. N., Elgbeili, G., Massart, R., Szyf, M., Liu, A., et al. (2015). DNA methylation mediates the impact of exposure to prenatal maternal stress on BMI and central adiposity in children at age 13(1/2) years: Project Ice Storm. Epigenetics. Advance online publication. doi:10.1080/15592294.2015.1063771 Google Scholar
Cao-Lei, L., Massart, R., Suderman, M. J., Machnes, Z., Elgbeili, G., Laplante, D. P., et al. (2014). DNA methylation signatures triggered by prenatal maternal stress exposure to a natural disaster: Project Ice Storm. PLOS ONE, 9, e107653. doi:10.1371/journal.pone.0107653 Google Scholar
Chaloner, A., & Greenwood-Van Meerveld, B. (2013). Sexually dimorphic effects of unpredictable early life adversity on visceral pain behavior in a rodent model. Journal of Pain, 14, 270–280. doi:10.1016/j.jpain.2012.11.008 Google Scholar
Champoux, M., Bennett, A., Shannon, C., Higley, J. D., Lesch, K. P., & Suomi, S. J. (2002). Serotonin transporter gene polymorphism, differential early rearing, and behavior in rhesus monkey neonates. Molecular Psychiatry, 7, 1058–1063. doi:10.1038/sj.mp.4001157 Google Scholar
Conti, G., Hansman, C., Heckman, J. J., Novak, M. F., Ruggiero, A., & Suomi, S. J. (2012). Primate evidence on the late health effects of early-life adversity. Proceedings of the National Academy of Sciences, 109, 8866–8871. doi:10.1073/pnas.1205340109 Google Scholar
Dannlowski, U., Kugel, H., Redlich, R., Halik, A., Schneider, I., Opel, N., et al. (2014). Serotonin transporter gene methylation is associated with hippocampal gray matter volume. Human Brain Mapping, 35, 5356–5367. doi:10.1002/hbm.22555 Google Scholar
Davis, E. P., & Pfaff, D. (2014). Sexually dimorphic responses to early adversity: Implications for affective problems and autism spectrum disorder. Psychoneuroendocrinology, 49, 11–25. doi:10.1016/j.psyneuen.2014.06.014 Google Scholar
Dettmer, A. M., Novak, M. A., Suomi, S. J., & Meyer, J. S. (2012). Physiological and behavioral adaptation to relocation stress in differentially reared rhesus monkeys: Hair cortisol as a biomarker for anxiety-related responses. Psychoneuroendocrinology, 37, 191–199. doi:10.1016/j.psyneuen.2011.06.003 Google Scholar
Graf, S., Nielsen, F. G., Kurtz, S., Huynen, M. A., Birney, E., Stunnenberg, H., et al. (2007). Optimized design and assessment of whole genome tiling arrays. Bioinformatics, 23, i195–i204. doi:10.1093/bioinformatics/btm200 Google Scholar
Grassi-Oliveira, R., Honeycutt, J. A., Holland, F. H., Ganguly, P., & Brenhouse, H. C. (2016). Cognitive impairment effects of early life stress in adolescents can be predicted with early biomarkers: Impacts of sex, experience, and cytokines. Psychoneuroendocrinology, 71, 19–30. doi:10.1016/j.psyneuen.2016.04.016 Google Scholar
Heim, C., & Nemeroff, C. B. (2001). The role of childhood trauma in the neurobiology of mood and anxiety disorders: Preclinical and clinical studies. Biological Psychiatry, 49, 1023–1039. doi:S000632230101157X Google Scholar
Hellman, A., & Chess, A. (2007). Gene body-specific methylation on the active X chromosome. Science, 315, 1141–1143.Google Scholar
Hotchkiss, R. D. (1948). The quantitative separation of purines, pyrimidines, and nucleosides by paper chromatography. Journal of Biological Chemistry, 175, 315–332.Google Scholar
Houtepen, L. C., Vinkers, C. H., Carrillo-Roa, T., Hiemstra, M., van Lier, P. A., Meeus, W., et al. (2016). Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans. Nature Communications, 7, 10967. doi:10.1038/ncomms10967 Google Scholar
Kaufman, J., Plotsky, P. M., Nemeroff, C. B., & Charney, D. S. (2000). Effects of early adverse experiences on brain structure and function: Clinical implications. Biological Psychiatry, 48, 778–790. doi:10.S0006-3223(00)00998-7 CrossRefGoogle ScholarPubMed
Klengel, T., Mehta, D., Anacker, C., Rex-Haffner, M., Pruessner, J. C., Pariante, C. M., et al. (2013). Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nature Neuroscience, 16, 33–41. doi:10.1038/nn.3275 Google Scholar
Kriaucionis, S., & Heintz, N. (2009). The nuclear DNA base 5-hydroxymethylcytosine is present in Purkinje neurons and the brain. Science, 324, 929–930. doi:10.1126/science.1169786 Google Scholar
Leussis, M. P., Freund, N., Brenhouse, H. C., Thompson, B. S., & Andersen, S. L. (2012). Depressive-like behavior in adolescents after maternal separation: Sex differences, controllability, and GABA. Developmental Neuroscience, 34, 210–217. doi:10.1159/000339162 Google Scholar
Levine, A., Cantoni, G. L., & Razin, A. (1991). Inhibition of promoter activity by methylation: Possible involvement of protein mediators. Proceedings of the National Academy of Sciences, 88, 6515–6518.Google Scholar
McEwen, B. S. (2000). Effects of adverse experiences for brain structure and function. Biological Psychiatry, 48, 721–731. doi:10.S0006-3223(00)00964-1 Google Scholar
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonte, B., Szyf, M., et al. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience, 12, 342–348. doi:10.1038/nn.2270 Google Scholar
McGowan, P. O., Sasaki, A., Huang, T. C., Unterberger, A., Suderman, M., Ernst, C., et al. (2008). Promoter-wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLOS ONE, 3, e2085. doi:10.1371/journal.pone.0002085 Google Scholar
McGowan, P. O., Suderman, M., Sasaki, A., Huang, T. C., Hallett, M., Meaney, M. J., et al. (2011). Broad epigenetic signature of maternal care in the brain of adult rats. PLOS ONE, 6, e14739. doi:10.1371/journal.pone.0014739 Google Scholar
Meaney, M. J., & Szyf, M. (2005). Maternal care as a model for experience-dependent chromatin plasticity? Trends in Neuroscience, 28, 456–463. doi:10.1016/j.tins.2005.07.006 Google Scholar
Mehta, D., Klengel, T., Conneely, K. N., Smith, A. K., Altmann, A., Pace, T. W., et al. (2013). Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder. Proceedings of the National Academy of Sciences, 110, 8302–8307. doi:10.1073/pnas.1217750110 Google Scholar
Mohandas, T., Sparkes, R. S., & Shapiro, L. J. (1981). Reactivation of an inactive human X chromosome: Evidence for X inactivation by DNA methylation. Science, 211, 393–396.Google Scholar
Moskalev, E. A., Zavgorodnij, M. G., Majorova, S. P., Vorobjev, I. A., Jandaghi, P., Bure, I. V., et al. (2011). Correction of PCR-bias in quantitative DNA methylation studies by means of cubic polynomial regression. Nucleic Acids Research, 39, e77. doi:10.1093/nar/gkr213 Google Scholar
Murgatroyd, C., Patchev, A. V., Wu, Y., Micale, V., Bockmuhl, Y., Fischer, D., et al. (2009). Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nature Neuroscience, 12, 1559–1566. doi:10.1038/nn.2436 Google Scholar
Power, C., Atherton, K., Strachan, D. P., Shepherd, P., Fuller, E., Davis, A., et al. (2007). Life-course influences on health in British adults: Effects of socio-economic position in childhood and adulthood. International Journal of Epidemiology, 36, 532–539.Google Scholar
Provencal, N., Suderman, M. J., Guillemin, C., Massart, R., Ruggiero, A., Wang, D., et al. (2012). The signature of maternal rearing in the methylome in rhesus macaque prefrontal cortex and T cells. Journal of Neuroscience, 32, 15626–15642. doi:10.1523/jneurosci.1470-12.2012 Google Scholar
Razin, A., & Cedar, H. (1993). DNA methylation and embryogenesis. Exs, 64, 343–357.Google Scholar
Razin, A., & Szyf, M. (1984). DNA methylation patterns: Formation and function. Biochimica Biophysica Acta, 782, 331–342.Google Scholar
Roth, T. L., Lubin, F. D., Funk, A. J., & Sweatt, J. D. (2009). Lasting epigenetic influence of early-life adversity on the BDNF gene. Biological Psychiatry, 65, 760–769. doi:10.1016/j.biopsych.2008.11.028 Google Scholar
Sinclair, K. D., Lea, R. G., Rees, W. D., & Young, L. E. (2007). The developmental origins of health and disease: Current theories and epigenetic mechanisms. Social and Reproductive Fertility, 64(Suppl.), 425–443.Google Scholar
Smyth, G. K. (2005). Limma: Linear models for microarray data. In Gentleman, V. C. R., Dudoit, S., Irizarry, R., & Huber, W. (Eds.), Bioinformatics and computational biology solutions using R and bioconductor (Vol. 1, pp. 397–420). New York: Springer.Google Scholar
Strahl, B. D., & Allis, C. D. (2000). The language of covalent histone modifications. Nature, 403, 41–45.Google Scholar
Suderman, M., McGowan, P. O., Sasaki, A., Huang, T. C., Hallett, M. T., Meaney, M. J., et al. (2012). Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus. Proceeding of the National Academy of Sciences, 109(Suppl. 2), 17266–17272. doi:10.1073/pnas.1121260109 Google Scholar
Suomi, S. J. (1991). Early stress and adult emotional reactivity in rhesus monkeys. Ciba Foundation Symposiums, 156, 171–183.Google Scholar
Szyf, M. (2011). DNA methylation, the early-life social environment and behavioral disorders. Journal of Neurodevelopmental Disorders, 3, 238–249. doi:10.1007/s11689-011-9079-2 Google Scholar
Szyf, M. (2012). The early-life social environment and DNA methylation. Clinical Genetics, 81, 341–349. doi:10.1111/j.1399-0004.2012.01843.x Google Scholar
Szyf, M. (2014). Examining peripheral DNA methylation in behavioral epigenetic and epigenetic psychiatry: Opportunities and challenges. Epigenomics, 6, 581–584. doi:10.2217/epi.14.57 Google Scholar
Szyf, M., Tang, Y. Y., Hill, K. G., & Musci, R. (2016). The dynamic epigenome and its implications for behavioral interventions: A role for epigenetics to inform disorder prevention and health promotion. Transactions in Behavior Medicine, 6, 55–62. doi:10.1007/s13142-016-0387-7 Google Scholar
Szyf, M., Weaver, I., & Meaney, M. (2007). Maternal care, the epigenome and phenotypic differences in behavior. Reproductive Toxicology, 24, 9–19.Google Scholar
Theil, E. C., & Zamenhof, S. (1963). Studies on 6-methylaminopurine (6-methyladenine) in bacterial deoxyribonucleic acid. Journal of Biological Chemistry, 238, 3058–3064.Google Scholar
Wang, D., Szyf, M., Benkelfat, C., Provencal, N., Turecki, G., Caramaschi, D., et al. (2012). Peripheral SLC6A4 DNA methylation is associated with in vivo measures of human brain serotonin synthesis and childhood physical aggression. PLOS ONE, 7, e39501. doi:10.1371/journal.pone.0039501 Google Scholar
Weaver, I. C., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., et al. (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 7, 847–854.Google Scholar
Weaver, I. C., Hellstrom, I. C., Brown, S. E., Andrews, S. D., Dymov, S., Diorio, J., et al. (2014). The methylated-DNA binding protein MBD2 enhances NGFI-A (egr-1)-mediated transcriptional activation of the glucocorticoid receptor. Philosophical Transactions of the Royal Society of London B: Biological Sciences, 369, 20130513. doi:10.1098/rstb.2013.0513 Google Scholar
Wu, T. P., Wang, T., Seetin, M. G., Lai, Y., Zhu, S., Lin, K., et al. (2016). DNA methylation on N-adenine in mammalian embryonic stem cells. Nature. Advance online publication. doi:10.1038/nature17640 Google Scholar
Wyatt, G. R. (1950). Occurrence of 5-methylcytosine in nucleic acids. Nature, 166, 237–238.Google Scholar
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