The Role of H3K9 Acetylation and Gene Expression in Different Brain Regions of Alzheimer’s Disease Patients
Dalileia Aparecida Santana, Amina Bedrat, Renato Puga, Gustavo Turecki, Naguib Mechawar, Tathyane Chaves Faria, Carolina Oliveira Gigek, Spencer LM Payão, Marı́lia de Arruda Cardoso Smith, Bernardo Lemos, Elizabeth Chen
Abstract
Aims: To evaluate H3K9 acetylation and gene expression profiles in three brain regions of Alzheimer’s disease (AD) patients and elderly controls, and to identify AD region-specific abnormalities. Methods: Brain samples of auditory cortex, hippocampus and cerebellum from AD patients and controls underwent chromatin immunoprecipitation sequencing, RNA sequencing and network analyses. Results: We found a hyperacetylation of AD cerebellum and a slight hypoacetylation of AD hippocampus. The transcriptome revealed differentially expressed genes in the hippocampus and auditory cortex. Network analysis revealed Rho GTPase-mediated mechanisms. Conclusions: These findings suggest that some crucial mechanisms, such as Rho GTPase activity and cytoskeletal organization, are differentially dysregulated in brain regions of AD patients at the epigenetic and transcriptomic levels, and might contribute toward future research on AD pathogenesis.