Hemispheric asymmetry in the human brain and in Parkinson's disease is linked to divergent epigenetic patterns in neurons.

Genome Biology
Peipei LiViviane Labrie

Abstract

Hemispheric asymmetry in neuronal processes is a fundamental feature of the human brain and drives symptom lateralization in Parkinson's disease (PD), but its molecular determinants are unknown. Here, we identify divergent epigenetic patterns involved in hemispheric asymmetry by profiling DNA methylation in isolated prefrontal cortex neurons from control and PD brain hemispheres. DNA methylation is fine-mapped at enhancers and promoters, genome-wide, by targeted bisulfite sequencing in two independent sample cohorts. We find that neurons of the human prefrontal cortex exhibit hemispheric differences in DNA methylation. Hemispheric asymmetry in neuronal DNA methylation patterns is largely mediated by differential CpH methylation, and chromatin conformation analysis finds that it targets thousands of genes. With aging, there is a loss of hemispheric asymmetry in neuronal epigenomes, such that hemispheres epigenetically converge in late life. In neurons of PD patients, hemispheric asymmetry in DNA methylation is greater than in controls and involves many PD risk genes. Epigenetic, transcriptomic, and proteomic differences between PD hemispheres correspond to the lateralization of PD symptoms, with abnormalities being most prevalen...Continue Reading

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Citations

Jul 8, 2020·International Journal of Molecular Sciences·Aintzane Urbizu, Katrin Beyer
Jan 7, 2021·Neurology. Neuroimmunology and Neuroinflammation·Mahmoud A AbdelRazekMarcelo Matiello
Aug 19, 2020·Nature Neuroscience·Lee L MarshallViviane Labrie
Aug 14, 2020·Laterality·Sebastian OcklenburgPatrick Friedrich
Jul 29, 2021·Neuropathology and Applied Neurobiology·Megha MurthyConceição Bettencourt
Aug 25, 2021·Brain Imaging and Behavior·Jinmei SunKai Wang

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Methods Mentioned

BETA
Profiler
RNA-seq
Flow Cytometry
Assay
PCR
chip

Software Mentioned

Cytoscape
Bismark
SNPer
GSEA
Ensemble
BS
Enrichment Map
edgeR
Trimmomatic
Profiler

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