Early life adversity alters normal sex-dependent developmental dynamics of DNA methylation.
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.
McGill University.
Renaud
R
Massart
McGill University.
Zsofia
Z
Nemoda
McGill University.
Matthew J
MJ
Suderman
Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Sheila
S
Sutti
Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Angela M
AM
Ruggiero
Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Amanda M
AM
Dettmer
Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Stephen J
SJ
Suomi
McGill University.
Moshe
M
Szyf
D000818:Animals; D019175:DNA Methylation / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D006801:Humans; D008016:Life Change Events; D008253:Macaca mulatta; D008297:Male; D008426:Maternal Deprivation; D010641:Phenotype; D012737:Sex Factors; D013315:Stress, Psychological / Q000150:complications*
Nature. 2000 Jan 6;403(6765):41-5
10638745
Biol Psychiatry. 2000 Oct 15;48(8):721-31
11063969
Biol Psychiatry. 2000 Oct 15;48(8):778-90
11063974
Biol Psychiatry. 2001 Jun 15;49(12):1023-39
11430844
Mol Psychiatry. 2002;7(10):1058-63
12476320
Bioinformatics. 2003 Jan 22;19(2):185-93
12538238
J Biol Chem. 1963 Sep;238:3058-64
14081924
Genes Brain Behav. 2003 Dec;2(6):336-40
14653305
Cell. 2004 Jan 23;116(2):281-97
14744438
Nat Neurosci. 2004 Aug;7(8):847-54
15220929
Nature. 1950 Aug 5;166(4214):237-8
15439258
Trends Neurosci. 2005 Sep;28(9):456-63
16054244
Proc Natl Acad Sci U S A. 1991 Aug 1;88(15):6515-8
1650472
Int J Epidemiol. 2007 Jun;36(3):532-9
17255345
Science. 2007 Feb 23;315(5815):1141-3
17322062
Soc Reprod Fertil Suppl. 2007;64:425-43
17491163
Reprod Toxicol. 2007 Jul;24(1):9-19
17561370
Bioinformatics. 2007 Jul 1;23(13):i195-204
17646297
PLoS One. 2008 May 07;3(5):e2085
18461137
Ciba Found Symp. 1991;156:171-83; discussion 183-8
1855411
J Biol Chem. 1948 Aug;175(1):315-32
18873306
Biol Psychiatry. 2009 May 1;65(9):760-9
19150054
Nat Neurosci. 2009 Mar;12(3):342-8
19234457
Science. 2009 May 15;324(5929):929-30
19372393
Nat Neurosci. 2009 Dec;12(12):1559-66
19898468
PLoS One. 2011 Feb 28;6(2):e14739
21386994
J Neurodev Disord. 2011 Sep;3(3):238-49
21484196
Nucleic Acids Res. 2011 Jun;39(11):e77
21486748
Psychoneuroendocrinology. 2012 Feb;37(2):191-9
21715101
Clin Genet. 2012 Apr;81(4):341-9
22236068
Proc Natl Acad Sci U S A. 2012 Jun 5;109(23):8866-71
22615410
PLoS One. 2012;7(6):e39501
22745770
Dev Neurosci. 2012;34(2-3):210-7
22776911
Proc Natl Acad Sci U S A. 2012 Oct 16;109 Suppl 2:17266-72
23045659
J Neurosci. 2012 Oct 31;32(44):15626-42
23115197
Nat Neurosci. 2013 Jan;16(1):33-41
23201972
J Pain. 2013 Mar;14(3):270-80
23348370
Proc Natl Acad Sci U S A. 2013 May 14;110(20):8302-7
23630272
Hum Brain Mapp. 2014 Nov;35(11):5356-67
24862560
Psychoneuroendocrinology. 2014 Nov;49:11-25
25038479
Philos Trans R Soc Lond B Biol Sci. 2014 Sep 26;369(1652):null
25135974
PLoS One. 2014 Sep 19;9(9):e107653
25238154
Epigenomics. 2014;6(6):581-4
25531252
Epigenetics. 2015;10(8):749-61
26098974
Nat Commun. 2016 Mar 21;7:10967
26997371
Transl Behav Med. 2016 Mar;6(1):55-62
27012253
Nature. 2016 Apr 21;532(7599):329-33
27027282
Psychoneuroendocrinology. 2016 Sep;71:19-30
27235636
Science. 1981 Jan 23;211(4480):393-6
6164095
Biochim Biophys Acta. 1984 Sep 10;782(4):331-42
6383476
EXS. 1993;64:343-57
8418954