Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation

  title={Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation},
  author={Rachel Yehuda and Nikolaos P. Daskalakis and Linda M. Bierer and Heather N. Bader and Torsten Klengel and Florian Holsboer and Elisabeth B. Binder},
  journal={Biological Psychiatry},
Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus
This study highlights that DNAm levels within regulatory regions of the FKBP5 locus show dynamic changes following a GC challenge and suggest that factors influencing the dynamics of this regulation may contribute to the previously reported alterations in DNAm associated with current and past ELS exposure.
DNA methylation at stress-related genes is associated with exposure to early life institutionalization.
A lasting impact of early severe social deprivation on methylation patterns in two stress-related genes, FKBP5 and SLC6A4, is suggested, linking early adversity and epigenetic variation in children.
No association between FKBP5 gene methylation and acute and long-term cortisol output
The findings did not reveal strong evidence for a robust effect of CT on FK BP5 intron 7 DNAM status, and FKBP5 DNAM levels were found to be unrelated to acute cortisol stress reactivity and long-term cortisol concentration in hair.
The effects of childhood maltreatment on epigenetic regulation of stress-response associated genes: an intergenerational approach
The hypothesis of a long-lasting impact of CM on the biological epigenetic regulation of stress-response mediators is supported and it is suggested for the first time that these specific epigenetic patterns might not be directly transmitted to the next generation.
Intergenerational Transmission of DNA Methylation Signatures Associated with Early Life Stress
The field of epigenetic transmission is just beginning to enter the epigenomic era by using genome-wide analyses, and approaches remain of strong interest to human studies, first in order to help to assess the relevance of the previous targeted studies, and second to discover new important epigenetic modifications of potential clinical importance.
Non-genetic transgenerational transmission of bipolar disorder: targeting DNA methyltransferases
Bipolar disorder has been shown to present a strong1 and complex2 genetic component, even though common variants found in genome-wide association studies still account for only a small fraction of BD heritability, and non-genetic mechanisms have a role in its risk and onset.
Epigenetics and the Exposome
Common techniques that are applied for untargeted approaches; and to measure regional modifications and gene-specific aberrations to measure epigenetic marks on a genomic scale are described.
Inter- and transgenerational inheritance of behavioral phenotypes
Epigenetic derepression of FKBP5 by aging and stress contributes to NF-ĸB-driven inflammation and cardiovascular risk
It is found that aging and stress synergize to epigenetically derepress FKBP5, a protein implicated in stress physiology, which provides molecular insights into stress-related disease and may point to novel biomarker and treatment possibilities.


The Tutsi genocide and transgenerational transmission of maternal stress: epigenetics and biology of the HPA axis
  • N. Perroud, E. Rutembesa, F. Karege
  • Biology, Psychology
    The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry
  • 2014
PTSD was associated with NR3C1 epigenetic modifications that were similarly found in the mothers and their offspring, modifications that may underlie the possible transmission of biological alterations of the HPA axis.
Allele-specific FKBP5 DNA demethylation mediates gene–childhood trauma interactions
It is found that a functional polymorphism altering chromatin interaction between the transcription start site and long-range enhancers in the FK506 binding protein 5 gene increased the risk of developing stress-related psychiatric disorders in adulthood by allele-specific, childhood trauma–dependent DNA demethylation in functional glucocorticoid response elements of FKBP5.
Site-specific methylation changes in the glucocorticoid receptor exon 1F promoter in relation to life adversity: systematic review of contributing factors
It is proposed that it is useful to examine whether methylation at specific sites within the promoter region may be particularly relevant to psychiatric vulnerability to stress-related outcomes.
Dynamic DNA methylation programs persistent adverse effects of early-life stress
It is found that neuronal activity controlled the ability of MeCP2 to regulate activity-dependent transcription of the Avp gene and induced epigenetic marking, which can dynamically control DNA methylation in postmitotic neurons to generate stable changes in Avp expression that trigger neuroendocrine and behavioral alterations that are frequent features in depression.
Epigenetic programming by maternal behavior
It is shown that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible, suggesting a causal relation among epigenomicState, GR expression and the maternal effect on stress responses in the offspring.
Glucocorticoid receptor activates poised FKBP51 locus through long-distance interactions.
The results indicate that the holo-GR is capable of activating transcription and evoking changes in chromatin structure through distant-acting enhancers.
Genetic variation in FKBP5 associated with the extent of stress hormone dysregulation in major depression
A significant interaction between disease status and FKBP5 risk allele carrier status (minor allele T) on GR‐stimulated FK BP5 mRNA expression was observed, suggesting that endocrine alterations in depressed patients are determined by genetic variants and may allow identification of specific subgroups.