Epigenetic modulation of AREL1 and increased HLA expression in brains of multiple system atrophy patients

Acta Neuropathologica Communications
Rasmus RydbirkSusana Aznar

Abstract

Multiple system atrophy (MSA) is a rare disease with a fatal outcome. To date, little is known about the molecular processes underlying disease development. Its clinical overlap with related neurodegenerative movement disorders underlines the importance for expanding the knowledge of pathological brain processes in MSA patients to improve distinction from similar diseases. In the current study, we investigated DNA methylation changes in brain samples from 41 MSA patients and 37 healthy controls. We focused on the prefrontal cortex, a moderately affected area in MSA. Using Illumina MethylationEPIC arrays, we investigated 5-methylcytosine (5mC) as well as 5-hydroxymethylcytosine (5hmC) changes throughout the genome. We identified five significantly different 5mC probes (adj. P < 0.05), of which one probe mapping to the AREL1 gene involved in antigen presentation was decreased in MSA patients. This decrease correlated with increased 5hmC levels. Further, we identified functional DNA methylation modules involved in inflammatory processes. As expected, the decreased 5mC levels on AREL1 was concordant with increased gene expression levels of both AREL1 as well as MHC Class I HLA genes in MSA brains. We also investigated whether these...Continue Reading

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Citations

Jul 10, 2020·JCI Insight·Kyle S ConwaySriram Venneti
Dec 23, 2020·Neuroscience Letters·Alexandra Pérez-Soriano, María J Martí
Dec 29, 2020·Neuropathology and Applied Neurobiology·Conceição BettencourtJanice L Holton
May 1, 2021·Biomolecules·Andrei SurguchovAlexei A Surguchev
Jul 29, 2021·Neuropathology and Applied Neurobiology·Megha MurthyConceição Bettencourt

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Methods Mentioned

BETA
amplicon sequencing
PCR
electrophoresis
Assay
ubiquitination
GTPase

Key Resources (RRID) Mentioned

SCR_015820
SCR_016152

Software Mentioned

Bumphunter
HOCOMOCO Human
MEME Suite
ChromHMM
FEM
qqman
MSA
impute
minfi
R

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