Fig. 1

Dexamethasone (DEX)-induced transient changes in hormonal, FKBP5 mRNA and methylation levels in blood. a Serum adrenocorticotropin (ACTH) and cortisol (CORT) levels as well as whole blood FKBP5 mRNA levels after an oral dose of DEX in 19 healthy male subjects are shown. Peripheral blood was drawn just before administration of DEX (time = 0) as well as 1, 3, 6, and 23 h thereafter. The mean and SEM are presented for each time point. Linear mixed models showed a significant effect across time for ACTH (p value = 1.26e−23), CORT (p value = 1.18e−24), and FKBP5 mRNA (p value < 2.2e−16) levels. p values of linear mixed models for each time point are indicated as follows: *≤ 0.05, **≤ 0.01, ***≤ 0.001. b Genome browser shot illustrating FKBP5 regulatory elements and DEX-induced methylation changes across the locus (hg19/chr6:35487554-35718452). Genes, genes located within the locus; CTCF-ChIA-PET, locations of CTCF factor-mediated chromatin interactions determined by Chromatin Interaction Analysis with Paired-End Tag (ChIA-PET) data extracted from lymphoblastoid cell line (GM12878, [26]). Chromatin interactions are represented by PET blocks connected with an horizontal line. CTCF-ChIP-seq and GR-Chip-seq, regions of transcription factor binding derived from chromatin immunoprecipitation (ChIP) experiments in multiple cell lines from the ENCODE project; TBS amplicons, locations of targeted bisulfite sequencing (TBS) amplicons; % methylation baseline, methylation levels across TBS amplicons at baseline; Max. ∆ % methylation, maximum methylation difference (delta) between any time points after DEX treatment and baseline for each TBS amplicons. Color-shaded regions highlight the main regulatory elements in the locus. c Example of CpG sites showing DEX-induced methylation changes. Boxplots represent the methylation levels per time point of CpGs located in the intronic enhancers (top), proximal enhancer (bottom left), and topologically associating domain (TAD) boundaries (bottom right). Methylations of individual CpG sites are shown except for the proximal enhancer plots where the mean methylation per amplicon is shown since this region covers 94 CpG sites. X axes indicate the coordinate of each site or region represented. Shaded boxes indicate sites where significant DEX effects were observed at FDR ≤ 0.05 and absolute delta methylation (T_i-baseline) ≥ 1% in at least one time point