DNA methylation patterns of FKBP5 regulatory regions in brain and blood of humanized mice and humans

• DOI: 10.1038/s41380-024-02430-x
• Publication Date: 2024-02-05T10:02:24Z
• Authors: Natan Yusupov; Simone Roeh; Laura Sotillos El...; Simon Chang; Srivaishnavi Loga...; Lidia Urbina-Treviño; Anna S. Fröhlich; Susann Sauer; Maik Ködel; Natalie Matosin; Darina Czamara; Jan M. Deussing; Elisabeth B. Binder
• Keywords: dNaM; Humanized mouse; FKBP5

Abstract Humanized mouse models can be used to explore human gene regulatory elements (REs), which frequently lie in non-coding and less conserved genomic regions. Epigenetic modifications of REs, also the context x environment interactions, have not yet been explored humanized models. We applied high-accuracy measurement DNA methylation (DNAm) via targeted bisulfite sequencing (HAM-TBS) investigate DNAm three tissues/brain regions (blood, prefrontal cortex hippocampus) mice carrying FK506-binding protein 5 ( FKBP5 ) gene, an important candidate associated with stress-related psychiatric disorders. functional intronic glucocorticoid-responsive (at introns 2, 5, 7) at baseline, cases differing genotype (rs1360780 single nucleotide polymorphism), following application synthetic glucocorticoid dexamethasone. compared patterns N = 58) those peripheral blood 447 89) postmortem brain 86). Overall, model seem recapitulate observed tissue. At this was a higher extent The animal recapitulated effects dexamethasone on DNAm, especially lesser DNAm. could thus assist reverse translation findings psychiatry that involve genetic epigenetic regulation elements.