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

Abstract：

BACKGROUND: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. RESULTS: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 prevalent in the hemisphere matched to side of symptom predominance. Hemispheric asymmetry and symptom lateralization in PD is linked to genes affecting neurodevelopment, immune activation, and synaptic transmission. PD patients with a long disease course have greater hemispheric asymmetry in neuronal epigenomes than those with a short disease course. CONCLUSIONS:Hemispheric differences in DNA methylation patterns are prevalent in neurons and may affect the progression and symptoms of PD.

journal_name

Genome Biol

journal_title

Genome biology

authors

Li P,Ensink E,Lang S,Marshall L,Schilthuis M,Lamp J,Vega I,Labrie V

doi

10.1186/s13059-020-01960-1

subject

Has Abstract

pub_date

2020-03-09 00:00:00

pages

61

issue

1

eissn

1474-7596

issn

1474-760X

pii

10.1186/s13059-020-01960-1

journal_volume

21

pub_type

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