Genome-Wide Methylation Profiling in the Thalamus of Scrapie Sheep

Hernaiz Martorell, A. (Universidad de Zaragoza) ; Sanz Fernández, A. (Universidad de Zaragoza) ; Sentre, S. ; Ranera, B. ; Lopez-Pérez, O. ; Zaragoza Fernández, P. (Universidad de Zaragoza) ; Badiola Díez, J.J. (Universidad de Zaragoza) ; Filali, H. ; Bolea Bailo, R. (Universidad de Zaragoza) ; Toivonen, J.M (Universidad de Zaragoza) ; Martín-Burriel, I. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.3389/fvets.2022.824677

Año: 2022

Publicado en: Frontiers in Veterinary Science 9 (2022), 824677 [16 pp.]
ISSN: 2297-1769

Factor impacto JCR: 3.2 (2022)

Categ. JCR: VETERINARY SCIENCES rank: 12 / 144 = 0.083 (2022) - Q1 - T1

Factor impacto CITESCORE: 3.8 - Veterinary (Q1)

Factor impacto SCIMAGO: 0.737 - Veterinary (miscellaneous) (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/C012-2014
Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/IIU-2023-2017
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-098711-B-I00
Financiación: info:eu-repo/grantAgreement/ES/MINECO/AGL2015-67945-P

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)