TY  - JOUR
A1  - Wiechmann, Tobias
A1  - Röh, Simone
A1  - Sauer, Susann
A1  - Czamara, Darina
A1  - Arloth, Janine
A1  - Ködel, Maik
A1  - Beintner, Madita
A1  - Knop, Lisanne
A1  - Menke, Andreas
A1  - Binder, Elisabeth B.
A1  - Provençal, Nadine
T1  - Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus
JF  - Clinical Epigenetics
N2  - Background
Epigenetic mechanisms may play a major role in the biological embedding of early-life stress (ELS). One proposed mechanism is that glucocorticoid (GC) release following ELS exposure induces long-lasting alterations in DNA methylation (DNAm) of important regulatory genes of the stress response. Here, we investigate the dynamics of GC-dependent methylation changes in key regulatory regions of the FKBP5 locus in which ELS-associated DNAm changes have been reported.

Results
We repeatedly measured DNAm in human peripheral blood samples from 2 independent cohorts exposed to the GC agonist dexamethasone (DEX) using a targeted bisulfite sequencing approach, complemented by data from Illumina 450K arrays. We detected differentially methylated CpGs in enhancers co-localizing with GC receptor binding sites after acute DEX treatment (1 h, 3 h, 6 h), which returned to baseline levels within 23 h. These changes withstood correction for immune cell count differences. While we observed main effects of sex, age, body mass index, smoking, and depression symptoms on FKBP5 methylation levels, only the functional FKBP5 SNP (rs1360780) moderated the dynamic changes following DEX. This genotype effect was observed in both cohorts and included sites previously shown to be associated with ELS.

Conclusion
Our 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.
KW  - DNA methylation
KW  - FKBP5
KW  - glucocorticoid receptor
KW  - early-life stress
KW  - targeted bisulfite sequencing
KW  - dexamethasone
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233673
VL  - 11
ER  -