Midtveisevaluering - Janani Sundaresan
Midtveisevaluering for ph.d.-graden ved Universitetet i Bergen for kandidat Janani Sundaresan
Janani Sundaresan er tilknyttet Klinisk institutt 1. Veiledere er Charalampos Tzoulis og Christian Dölle.
Role of Histone acetylation in Parkinson's Disease
The etiology of Parkinson’s disease (PD) is mostly unaccounted for. Based on previous evidence of neuronal metabolic defects in PD, we hypothesized that altered histone acetylation may be implicated in the disease process. Our previous work suggested alteration in some of the histone acetylation profile, in particular H3K27, between PD and age matched control brains. Here, we compare genome-wide enrichment of H3K27ac in the pre-frontal cortex (BA9) of PD individuals against age matched neurologically normal controls. Chromatin immunoprecipitation sequencing analysis indicates that H3K27 hyperacetylation occurs throughout the genome but is overrepresented among genes previously associated with PD. Intriguingly, we find strong evidence that H3K27 acetylation is decoupled from gene expression in PD. Our results replicate across two independent cohorts and establish aberrant histone acetylation as an important element of the molecular pathophysiology of PD.