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

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: DNA methylation patterns of FKBP5 regulatory regions in brain and blood of humanized mice and humans
Συγγραφείς: Yusupov, Natan, Roeh, Simone, Sotillos Elliott, Laura, Chang, Simon, Loganathan, Srivaishnavi, Urbina-Treviño, Lidia, Fröhlich, Anna, Sauer, Susann, Ködel, Maik, Matosin, Natalie, Czamara, Darina, Deussing, Jan, Binder, Elisabeth
Πηγή: http://lobid.org/resources/99370675519006441#!, 29(5):1510-1520.
Έτος έκδοσης: 2024
Συλλογή: Publisso (ZB MED-Publikationsportal Lebenswissenschaften)
Θεματικοί όροι: DNA Methylation/genetics [MeSH], Prefrontal Cortex/metabolism [MeSH], /692/699/476, Polymorphism, Single Nucleotide/genetics [MeSH], Mice, Transgenic [MeSH], Male [MeSH], /38/47, /64/110, Epigenesis, Genetic/genetics [MeSH], Hippocampus/metabolism [MeSH], /38/23, Female [MeSH], Adult [MeSH], Humans [MeSH], Middle Aged [MeSH], Animals [MeSH], Tacrolimus Binding Proteins/metabolism [MeSH], Mice [MeSH], Article, Glucocorticoids/pharmacology [MeSH], Brain/metabolism [MeSH], Tacrolimus Binding Proteins/genetics [MeSH], Regulatory Sequences, Nucleic Acid/genetics [MeSH], Genotype [MeSH], /631/378, Dexamethasone/pharmacology [MeSH]
Περιγραφή: AbstractHumanized 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 gene REs, also in the context of gene x environment interactions, have not yet been explored in humanized mouse models. We applied high-accuracy measurement of DNA methylation (DNAm) via targeted bisulfite sequencing (HAM-TBS) to investigate DNAm in three tissues/brain regions (blood, prefrontal cortex and hippocampus) of mice carrying the human FK506-binding protein 5 (FKBP5) gene, an important candidate gene associated with stress-related psychiatric disorders. We explored DNAm in three functional intronic glucocorticoid-responsive elements (at introns 2, 5, and 7) of FKBP5 at baseline, in cases of differing genotype (rs1360780 single nucleotide polymorphism), and following application of the synthetic glucocorticoid dexamethasone. We compared DNAm patterns in the humanized mouse (N = 58) to those in human peripheral blood (N = 447 and N = 89) and human postmortem brain prefrontal cortex (N = 86). Overall, DNAm patterns in the humanized mouse model seem to recapitulate DNAm patterns observed in human tissue. At baseline, this was to a higher extent in brain tissue. The animal model also recapitulated effects of dexamethasone on DNAm, especially in peripheral blood and to a lesser extent effects of genotype on DNAm. The humanized mouse model could thus assist in reverse translation of human findings in psychiatry that involve genetic and epigenetic regulation in non-coding elements.
Τύπος εγγράφου: article in journal/newspaper
Γλώσσα: English
Relation: https://repository.publisso.de/resource/frl:6504977; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189813/
DOI: 10.1038/s41380-024-02430-x
Διαθεσιμότητα: https://repository.publisso.de/resource/frl:6504977
https://doi.org/10.1038/s41380-024-02430-x
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189813/
Rights: https://creativecommons.org/licenses/by/4.0/
Αριθμός Καταχώρησης: edsbas.210B99F8
Βάση Δεδομένων: BASE
Περιγραφή
DOI:10.1038/s41380-024-02430-x