112390 20240319080947.0 doi 10.3389/fvets.2022.824677 sideral 128291 ART-2022-128291 eng Hernaiz Martorell, A. Universidad de Zaragoza (orcid)0000-0002-6806-9990 Genome-Wide Methylation Profiling in the Thalamus of Scrapie Sheep 2022 Access copy available to the general public Unrestricted Scrapie is a neurodegenerative disorder belonging to the group of transmissible spongiform encephalopathy (TSE). Scrapie occurs in sheep and goats, which are considered good natural animal models of these TSE. Changes in DNA methylation occur in the central nervous system (CNS) of patients suffering from prion-like neurodegenerative diseases, such as Alzheimer''s disease. Nevertheless, potential DNA methylation alterations have not yet been investigated in the CNS of any prion disease model or naturally infected cases, neither in humans nor in animals. Genome-wide DNA methylation patterns were studied in the thalamus obtained from sheep naturally infected with scrapie at a clinical stage (n = 4) and from controls (n = 4) by performing a whole-genome bisulfite sequencing (WGBS) analysis. Ewes carried the scrapie-susceptible ARQ/ARQ PRNP genotype and were sacrificed at a similar age (4–6 years). Although the average genomic methylation levels were similar between the control and the scrapie animals, we identified 8, 907 significant differentially methylated regions (DMRs) and 39 promoters (DMPs). Gene Ontology analysis revealed that hypomethylated DMRs were enriched in genes involved in transmembrane transport and cell adhesion, whereas hypermethylated DMRs were related to intracellular signal transduction genes. Moreover, genes highly expressed in specific types of CNS cells and those previously described to be differentially expressed in scrapie brains contained DMRs. Finally, a quantitative PCR (qPCR) validation indicated differences in the expression of five genes (PCDH19, SNCG, WDR45B, PEX1, and CABIN1) that matched the methylation changes observed in the genomic study. Altogether, these results suggest a potential regulatory role of DNA methylation in prion neuropathology. Copyright © 2022 Hernaiz, Sanz, Sentre, Ranera, Lopez-Pérez, Zaragoza, Badiola, Filali, Bolea, Toivonen and Martín-Burriel. info:eu-repo/grantAgreement/ES/DGA/C012-2014 info:eu-repo/grantAgreement/ES/DGA-FSE/IIU-2023-2017 info:eu-repo/grantAgreement/ES/MICINN/RTI2018-098711-B-I00 info:eu-repo/grantAgreement/ES/MINECO/AGL2015-67945-P info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 3.2 2022 VETERINARY SCIENCES 12 / 144 = 0.083 2022 Q1 T1 0.737 2022 Veterinary (miscellaneous) 2022 Q1 3.8 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Sanz Fernández, A. Universidad de Zaragoza (orcid)0000-0001-6489-8399 Sentre, S. Ranera, B. Lopez-Pérez, O. (orcid)0000-0003-2454-2114 Zaragoza Fernández, P. Universidad de Zaragoza (orcid)0000-0001-5740-0185 Badiola Díez, J.J. Universidad de Zaragoza (orcid)0000-0002-7173-7216 Filali, H. (orcid)0000-0003-3352-740X Bolea Bailo, R. Universidad de Zaragoza (orcid)0000-0002-2746-3932 Toivonen, J.M Universidad de Zaragoza (orcid)0000-0002-7243-1737 Martín-Burriel, I. Universidad de Zaragoza (orcid)0000-0001-6016-4726 1001 420 Universidad de Zaragoza Dpto. Anatom.,Embri.Genét.Ani. Área Genética 1009 773 Universidad de Zaragoza Dpto. Patología Animal Área Sanidad Animal 9 (2022), 824677 [16 pp.] Front. vet. sci. Frontiers in Veterinary Science 2297-1769 2311290 http://zaguan.unizar.es/record/112390/files/texto_completo.pdf Versión publicada 2423876 http://zaguan.unizar.es/record/112390/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:112390 articulos driver 2024-03-18-12:43:29 ARTICLE