Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus
Abstract 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 st...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-05-01
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| Series: | Clinical Epigenetics |
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| Online Access: | http://link.springer.com/article/10.1186/s13148-019-0682-5 |
| _version_ | 1818944936442068992 |
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| author | Tobias Wiechmann Simone Röh Susann Sauer Darina Czamara Janine Arloth Maik Ködel Madita Beintner Lisanne Knop Andreas Menke Elisabeth B. Binder Nadine Provençal |
| author_facet | Tobias Wiechmann Simone Röh Susann Sauer Darina Czamara Janine Arloth Maik Ködel Madita Beintner Lisanne Knop Andreas Menke Elisabeth B. Binder Nadine Provençal |
| author_sort | Tobias Wiechmann |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-20T07:51:08Z |
| format | Article |
| id | doaj.art-10db9c90f3fa45fd97eb0ae03b467f8e |
| institution | Directory Open Access Journal |
| issn | 1868-7075 1868-7083 |
| language | English |
| last_indexed | 2024-12-20T07:51:08Z |
| publishDate | 2019-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-10db9c90f3fa45fd97eb0ae03b467f8e2022-12-21T19:47:49ZengBMCClinical Epigenetics1868-70751868-70832019-05-0111111410.1186/s13148-019-0682-5Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locusTobias Wiechmann0Simone Röh1Susann Sauer2Darina Czamara3Janine Arloth4Maik Ködel5Madita Beintner6Lisanne Knop7Andreas Menke8Elisabeth B. Binder9Nadine Provençal10Department of Translational Research in Psychiatry, Max Planck Institute of PsychiatryDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryDepartment of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of WuerzburgDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryDepartment of Translational Research in Psychiatry, Max Planck Institute of PsychiatryAbstract 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.http://link.springer.com/article/10.1186/s13148-019-0682-5DNA methylationFKBP5Glucocorticoid receptorEarly-life stressTargeted bisulfite sequencingDexamethasone |
| spellingShingle | Tobias Wiechmann Simone Röh Susann Sauer Darina Czamara Janine Arloth Maik Ködel Madita Beintner Lisanne Knop Andreas Menke Elisabeth B. Binder Nadine Provençal Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus Clinical Epigenetics DNA methylation FKBP5 Glucocorticoid receptor Early-life stress Targeted bisulfite sequencing Dexamethasone |
| title | Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus |
| title_full | Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus |
| title_fullStr | Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus |
| title_full_unstemmed | Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus |
| title_short | Identification of dynamic glucocorticoid-induced methylation changes at the FKBP5 locus |
| title_sort | identification of dynamic glucocorticoid induced methylation changes at the fkbp5 locus |
| topic | DNA methylation FKBP5 Glucocorticoid receptor Early-life stress Targeted bisulfite sequencing Dexamethasone |
| url | http://link.springer.com/article/10.1186/s13148-019-0682-5 |
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