The role of H3K9 acetylation and gene expression in different brain regions of Alzheimer’s disease patients

Author:

Santana Daliléia A1ORCID,Bedrat Amina2ORCID,Puga Renato D3ORCID,Turecki Gustavo4ORCID,Mechawar Naguib4ORCID,Faria Tathyane C1ORCID,Gigek Carolina O5ORCID,Payão Spencer LM6ORCID,Smith Marília AC1ORCID,Lemos Bernardo2ORCID,Chen Elizabeth S12ORCID

Affiliation:

1. Department of Morphology & Genetics, Universidade Federal de São Paulo (UNIFESP), São Paulo,SP, 04023-062, Brazil

2. Department of Environmental Health & Molecular & Integrative Physiological Sciences Program, Harvard TH Chan School of Public Health, Boston, MA 02115-5810, USA

3. Hermes Pardini Institute, São Paulo, SP, 04038-030, Brazil

4. Department of Psychiatry, Douglas Hospital Research Center, McGill University, Montreal, QC, H4H1R3, Canada

5. Department of Pathology, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, 04023-062, Brazil

6. Department of Genetics, Blood Center, Faculdade de Medicina de Marília (FAMEMA), Marília, SP, 17519-050, Brazil

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.

Funder

Canada First Research Excellence Fund

Conselho Nacional de Desenvolvimento Científico e Tecnológico

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior

Fonds de Recherche du Québec – Santé

Fundação de Amparo à Pesquisa do Estado de São Paulo

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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