Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions

Klengel, Torsten, Mehta, Divya, Anacker, Christoph, Rex-Haffner, Monika, Pruessner, Jens C., Pariante, Carmine M., Pace, Thaddeus W. W., Mercer, Kristina B., Mayberg, Helen S., Bradley, Bekh, Nemeroff, Charles B., Holsboer, Florian, Heim, Christine M., Ressler, Kerry J., Rein, Theo and Binder, Elisabeth B. (2013) Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nature Neuroscience, 16 1: 33-41. doi:10.1038/nn.3275


Author Klengel, Torsten
Mehta, Divya
Anacker, Christoph
Rex-Haffner, Monika
Pruessner, Jens C.
Pariante, Carmine M.
Pace, Thaddeus W. W.
Mercer, Kristina B.
Mayberg, Helen S.
Bradley, Bekh
Nemeroff, Charles B.
Holsboer, Florian
Heim, Christine M.
Ressler, Kerry J.
Rein, Theo
Binder, Elisabeth B.
Title Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions
Journal name Nature Neuroscience   Check publisher's open access policy
ISSN 1097-6256
1546-1726
Publication date 2013
Sub-type Article (original research)
DOI 10.1038/nn.3275
Open Access Status
Volume 16
Issue 1
Start page 33
End page 41
Total pages 9
Place of publication New York, NY, United States
Publisher Nature Publishing
Abstract Although the fact that genetic predisposition and environmental exposures interact to shape development and function of the human brain and, ultimately, the risk of psychiatric disorders has drawn wide interest, the corresponding molecular mechanisms have not yet been elucidated. We found that a functional polymorphism altering chromatin interaction between the transcription start site and long-range enhancers in the FK506 binding protein 5 (FKBP5) gene, an important regulator of the stress hormone system, 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. This demethylation was linked to increased stress-dependent gene transcription followed by a long-term dysregulation of the stress hormone system and a global effect on the function of immune cells and brain areas associated with stress regulation. This identification of molecular mechanisms of genotype-directed long-term environmental reactivity will be useful for designing more effective treatment strategies for stress-related disorders.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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Created: Fri, 24 Oct 2014, 17:20:12 EST by Sylvie Pichelin on behalf of Queensland Brain Institute