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| Pàgina inicial > Articles > Articles publicats > An Integrative Analysis of DNA Methylation Pattern in Myotonic Dystrophy Type 1 Samples Reveals a Distinct DNA Methylation Profile between Tissues and a Novel Muscle-Associated Epigenetic Dysregulation |
(Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol) (Institut Germans Trias i Pujol) (Institut de Recerca Sant Joan de Déu) (Hospital del Mar (Barcelona, Catalunya)) (Institut d'Investigació Biomèdica Sant Pau) (Institut d'Investigació Biomèdica Sant Pau) (Institut Germans Trias i Pujol) (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol) (Institut Germans Trias i Pujol) (Institut Germans Trias i Pujol)| Data: | 2022 |
| Resum: | Myotonic dystrophy type 1 (DM1) is a progressive, non-treatable, multi-systemic disorder. To investigate the contribution of epigenetics to the complexity of DM1, we compared DNA methy-lation profiles of four annotated CpG islands (CpGis) in the DMPK locus and neighbouring genes, in distinct DM1 tissues and derived cells, representing six DM1 subtypes, by bisulphite sequencing. In blood, we found no differences in CpGi 74, 43 and 36 in DNA methylation profile. In contrast, a CTCF1 DNA methylation gradient was found with 100% methylation in congenital cases, 50% in childhood cases and 13% in juvenile cases. CTCF1 methylation correlated to disease severity and CTG expansion size. Notably, 50% of CTCF1 methylated cases showed methylation in the CTCF2 regions. Additionally, methylation was associated with maternal transmission. Interestingly, the evaluation of seven families showed that unmethylated mothers passed on an expansion of the CTG repeat, whereas the methylated mothers transmitted a contraction. The analysis of patient-derived cells showed that DNA methylation profiles were highly preserved, validating their use as faithful DM1 cellular models. Importantly, the comparison of DNA methylation levels of distinct DM1 tissues revealed a novel muscle-specific epigenetic signature with methylation of the CTCF1 region accompanied by demethylation of CpGi 43, a region containing an alternative DMPK promoter, which may decrease the canonical promoter activity. Altogether, our results showed a distinct DNA methylation profile across DM1 tissues and uncovered a novel and dual epigenetic signature in DM1 muscle samples, providing novel insights into the epigenetic changes associated with DM1. |
| Ajuts: | Instituto de Salud Carlos III PI18/00713 Instituto de Salud Carlos III IFI20/00022 Instituto de Salud Carlos III CPII19/00021 Ministerio de Ciencia e Innovación PID2020-118730RB-I00 Ministerio de Ciencia e Innovación 23557 European Commission. Horizon 2020 713673 |
| Nota: | Altres ajuts: AFM-Telethon (Trampoline Grant #21108); Fondos FEDER; Fundació Bancària La Caixa (ID 100010434, fellowship code LCF/BQ/IN18/11660019; CERCA program/Government of Catalonia. |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | Myotonic dystrophy ; CpG islands ; DNA methylation ; Epigenetics ; Phenotype severity ; DM1 biopsies ; Cellular models |
| Publicat a: | Biomedicines, Vol. 10 Núm. 6 (june 2022) , p. 1372, ISSN 2227-9059 |
