Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats

McGowan, Patrick O.; Suderman, Matthew; Sasaki, Aya; Huang, Tony Chieh-Ting; Hallett, Michael; Meaney, Michael J.; Szyf, Moshe

doi:10.1371/journal.pone.0014739

Cited by 412 publications

(289 citation statements)

References 54 publications

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“…Nevertheless, although less striking, there are differences in the frequency of methylation at other CpG sites on the exon 1 7 promoter [30,86]. Indeed, studies using methylation-dependent DNA precipitation with high coverage tiling arrays across chromosome 18 in the rat, which includes the GR gene, reveal broad regions that differ in cytosine methylation [87].…”

Section: The Epigenetics Of Phenotypic Plasticitymentioning

confidence: 99%

Environmental regulation of the neural epigenome

et al. 2011

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a b s t r a c tParental effects are a major source of phenotypic plasticity. Moreover, there is evidence from studies with a wide range of species that the relevant parental signals are influenced by the quality of the parental environment. The link between the quality of the environment and the nature of the parental signal is consistent with the idea that parental effects, whether direct or indirect, might serve to influence the phenotype of the offspring in a manner that is consistent with the prevailing environmental demands. In this review we explore recent studies from the field of 'environmental epigenetics' that suggest that (1) DNA methylation states are far more variable than once thought and that, at least within specific regions of the genome, there is evidence for both demethylation and remethylation in post-mitotic cells and (2) that such remodeling of DNA methylation can occur in response to environmentally-driven, intracellular signaling pathways. Thus, studies of variation in mother-offspring interactions in rodents suggest that parental signals operate during pre-and/ or post-natal life to influence the DNA methylation state at specific regions of the genome leading to sustained changes in gene expression and function. We suggest that DNA methylation is a candidate mechanism for parental effects on phenotypic variation.

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Section: The Epigenetics Of Phenotypic Plasticitymentioning

confidence: 99%

Environmental regulation of the neural epigenome

et al. 2011

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“…Differences in maternal care also affect the expression of hundreds of genes in the hippocampus, suggesting a broad response of the DNA to early life experience [18]. DNA methylation and chromatin changes affect broad genomic regions [24]. For example, McGowan et al showed that a large gene cluster containing the entire family of the protocadherin genes (associated with many neurodevelopmental processes like axon guidance and dendrite branching) is epigenetically programmed by maternal care; the entire cluster exhibited reduced expression, increased DNA methylation, and altered chromatin modification in low-LG adult offspring [24].…”

Section: Essaymentioning

confidence: 99%

“…DNA methylation and chromatin changes affect broad genomic regions [24]. For example, McGowan et al showed that a large gene cluster containing the entire family of the protocadherin genes (associated with many neurodevelopmental processes like axon guidance and dendrite branching) is epigenetically programmed by maternal care; the entire cluster exhibited reduced expression, increased DNA methylation, and altered chromatin modification in low-LG adult offspring [24]. It is tempting to speculate that these responses evolved to adapt animals to anticipated dynamic challenges in the environment [25].…”

Section: Essaymentioning

confidence: 99%

“…Remarkably, Suderman et al showed that the response in human brains to early life experience is broad as it is in rats and monkeys and is evolutionary conserved with a striking overall similarity between rat and human brains [35]. The PROTOCADHERIN gene family cluster which showed cluster-wide DNA methylation differences between high-and low-LG offspring adult rats [24] is differentially methylated between adult humans who were abused as children and control adults as well [35]. This evolutionary conservation of the epigenetic response of the same cluster of a gene family presents a strong argument that early life experience alters epigenetic programming in the brain in humans.…”

Section: Translation To Humans; Evidence For Epigenetic Consequences mentioning

confidence: 99%

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The dynamic epigenome and its implications for behavioral interventions: a role for epigenetics to inform disorder prevention and health promotion

Szyf

Tang

Hill

et al. 2016

Behav. Med. Pract. Policy Res.

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The emerging field of behavioral epigenetics is producing a growing body of evidence that early life experience and social exposure can alter the way by which genes are marked with DNA methylation. We hypothesize that changes in DNA methylation as well as other epigenetic markers could generate stable phenotypes. Early life adversity appears to result in altered DNA methylation of genes in the brain and peripheral tissues, and these changes are associated with adverse phenotypic changes. Although the data are still sparse, early epigenetic studies have provided a proof of principle that experiences and the environment leave marks on genes, and thus suggest molecular and physical mechanisms for the epidemiological concept of gene-environment interaction. The main attraction of DNA methylation for type I (TI) translational prevention science is the fact that, different from genetic changes that are inherited from our ancestors, DNA methylation is potentially preventable and reversible and, therefore, there is a prospect of epigenetically targeted interventions. In addition, DNA methylation markers might provide an objective tool for assessing effects of early adverse experience on individual risks as well as providing objective measures of progress of an intervention. In spite of this great potential promise of the emerging field of social and translational epigenetics, many practical challenges remain that must be addressed before behavioral epigenetics could become translational epigenetics.

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“…Dès 2004, les groupes de M. Szyf et de M. Meaney montrèrent que, chez le rat, la qualité des soins maternels durant la période postnatale conditionne pour la vie la réactivité au stress de leur progéniture [3]. Ces soins modifient, dans l'hippocampe, l'épigénome d'un gène clé, celui qui code le récepteur aux glucocorticoïdes, mais également l'épigénome de réseaux de gènes [4]. Des mécanismes semblables opèrent chez le rongeur, le macaque et l'humain [5,6], montrant la conservation entre les espèces des mécanismes impliqués dans de tels processus d'adaptation à l'environnement.…”

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