RT Journal Article
SR Electronic
T1 Genome-wide dysregulation of histone acetylation in the Parkinson’s disease brain
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 785550
DO 10.1101/785550
A1 Lilah Toker
A1 Gia T Tran
A1 Janani Sundaresan
A1 Ole-Bjørn Tysnes
A1 Guido Alves
A1 Kristoffer Haugarvoll
A1 Gonzalo S Nido
A1 Christian Dölle
A1 Charalampos Tzoulis
YR 2020
UL http://biorxiv.org/content/early/2020/04/02/785550.abstract
AB Parkinson disease (PD) is a complex neurodegenerative disorder of largely unknown etiology. While several genetic risk factors have been identified, the involvement of epigenetics in the pathophysiology of PD is mostly unaccounted for. We conducted a histone acetylome-wide association study in PD, using brain tissue from two independent cohorts of cases and controls. Immunoblotting revealed increased acetylation at several histone sites in PD, with the most prominent change observed for H3K27, a marker of active promoters and enhancers. Chromatin immunoprecipitation sequencing (ChIP-seq) further indicated that H3K27 hyperacetylation in the PD brain is a genome-wide phenomenon, with a strong predilection for genes implicated in the disease, including SNCA, PARK7, PRKN and MAPT. Integration of the ChIP-seq with transcriptomic data revealed that the correlation between promoter H3K27 acetylation and gene expression is attenuated in PD patients, suggesting that H3K27 acetylation may be decoupled from transcription in the PD brain. Our findings strongly suggest that dysregulation of histone acetylation plays an important role in the pathophysiology of PD and identify novel epigenetic signatures associated with the disease.ChIP-seqchromatin immunoprecipitation sequencingCtrlcontrolDARdifferentially acetylated regionEGLeffective gene lengthGWASgenome-wide association studyHAThistone acetyltransferaseHDAChistone deacetylaseL-DOPAlevodopamtDNAmitochondrial DNAMSPsMarker Site ProfilesNADnicotinamide adenine dinucleotideNBBNetherlands Brain BankPDParkinson’s diseasePFCPrefrontal cortexPMIPostmortem intervalPWPark WestRiPReads in peaksRLERelative Log ExpressionSNcsubstantia nigra pars compactaTSStranscription start siteWBWestern blotWESwhole exome sequencing