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早年逆境会改变DNA甲基化正常的性别依赖性发育动态。

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

作者信息

Massart Renaud, Nemoda Zsofia, Suderman Matthew J, Sutti Sheila, Ruggiero Angela M, Dettmer Amanda M, Suomi Stephen J, Szyf Moshe

机构信息

McGill University.

Eunice Kennedy Shriver National Institute of Child Health and Human Development.

出版信息

Dev Psychopathol. 2016 Nov;28(4pt2):1259-1272. doi: 10.1017/S0954579416000833. Epub 2016 Sep 30.

DOI:10.1017/S0954579416000833
PMID:27687908
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6590057/
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.

摘要

对啮齿动物、非人类灵长类动物和人类的研究表明，表观遗传过程在早期生活经历和成年表型之间起中介作用。然而，儿童发育过程中表观遗传程序的正常演变、性别影响以及早期生活逆境对这些轨迹的影响尚未得到充分理解。本研究绘制了恒河猴从出生后第14天到2岁的雄性和雌性CD3 + T淋巴细胞全基因组DNA甲基化变化图谱，并确定了母婴分离对DNA甲基化谱的影响。我们在此表明，DNA甲基化谱从出生到青春期不断演变，且具有性别依赖性。DNA甲基化变化伴随着强制断奶，减弱了雄性和雌性之间的差异。出生时的母婴分离会改变DNA甲基化谱的正常演变，并靶向那些在后期母婴分离（即断奶）时也会受到影响的基因。我们的结果表明，早期生活事件会动态干扰DNA甲基化谱的正常发育演变，并且这些变化受性别影响很大。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fd0/6590057/9c46e8579aa8/nihms-1024433-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fd0/6590057/67e5a001e3a9/nihms-1024433-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fd0/6590057/d66d1c401d5f/nihms-1024433-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fd0/6590057/b526a4088eb6/nihms-1024433-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fd0/6590057/9c46e8579aa8/nihms-1024433-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fd0/6590057/67e5a001e3a9/nihms-1024433-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fd0/6590057/d66d1c401d5f/nihms-1024433-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fd0/6590057/b526a4088eb6/nihms-1024433-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fd0/6590057/9c46e8579aa8/nihms-1024433-f0004.jpg

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