Mitochondrial stress-induced H4K12 hyperacetylation dysregulates transcription in Parkinson's disease.

ABSTRACT: Aberrant epigenetic modification has been implicated in the pathogenesis of Parkinson's disease (PD), which is characterized by the irreversible loss of dopaminergic (DAergic) neurons. However, the mechanistic landscape of histone acetylation (ac) in PD has yet to be fully explored. Herein, we mapped the proteomic acetylation profiling changes at core histones H4 and thus identified H4K12ac as a key epigenomic mark in dopaminergic neuronal cells as well as in MitoPark animal model of PD. Notably, the significantly elevated H4K12ac deposition in post-mortem PD brains highlights its clinical relevance to human PD. Increased histone acetyltransferase (HAT) activity and decreased histone deacetylase 2 (HDAC2) and HDAC4 were found in experimental PD cell models, suggesting the HAT/HDAC i

SUBMITTER: Huang M 

PROVIDER: S-EPMC11345260 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature