Startseite
English
Erweiterte Suche
Durchblättern nach ...
Publikationen im Überblick
Ansprechpartner
Hilfe
Verlagsversion
DOI
PMC
 |
Open Access Gold |
|
möglich sobald bei der ZB eingereicht worden ist.
Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus.
Clin. Epigenet. 11:83 (2019)
BackgroundEpigenetic 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.ResultsWe 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 (1h, 3h, 6h), which returned to baseline levels within 23h. 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.ConclusionOur 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.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten
[➜Einloggen]
Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Dna Methylation ; Fkbp5 ; Glucocorticoid Receptor ; Early-life Stress ; Targeted Bisulfite Sequencing ; Dexamethasone; Dna Methylation; Childhood Adversity; Life Events; Gene; Ctcf; Stress; Dexamethasone; Expression; Receptor; Binding
ISSN (print) / ISBN
1868-7075
e-ISSN
1868-7083
Zeitschrift
Clinical Epigenetics
Quellenangaben
Band: 11,
Heft: 1,
Artikelnummer: 83
Verlag
Springer
Verlagsort
Berlin : Heidelberg
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Computational Biology (ICB)