Single-Base Resolution Mapping of 5-Hydroxymethylcytosine Modifications in Hippocampus of Alzheimer’s Disease Subjects

• Published in: Journal of molecular neuroscience Vol. 63; no. 2; pp. 185 - 197
• Main Authors: Ellison, Elizabeth M., Bradley-Whitman, Melissa A., Lovell, Mark A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2017; Springer Nature B.V
• Subjects: 5-Methylcytosine - analogs & derivatives; 5-Methylcytosine - metabolism; Aged, 80 and over; Alzheimer Disease - genetics; Alzheimer Disease - metabolism; Alzheimer's disease; Biomedical and Life Sciences; Biomedicine; Cancer; Case-Control Studies; Cell Biology; Cytology; Cytosine; Deoxyribonucleic acid; DNA; DNA Methylation; DNA microarrays; Embryogenesis; Embryonic growth stage; Energy metabolism; Epigenesis, Genetic; Epigenetics; Female; Gene expression; Gene mapping; Genomes; Hippocampus; Hippocampus - metabolism; Humans; Male; Mapping; Metabolism; Methylation; Neurochemistry; Neurodegeneration; Neurodegenerative diseases; Neurology; Neurosciences; Protein structure; Protein turnover; Proteomics; Signaling; Transcription; Epigenetics; Alzheimer’s disease; 5-Hydroxymethylcytosine; Hippocampus
• ISSN: 0895-8696; 1559-1166; 1559-1166
• DOI: 10.1007/s12031-017-0969-y

Epigenetic modifications to cytosine have been shown to regulate transcription in cancer, embryonic development, and recently neurodegeneration. While cytosine methylation studies are now common in neurodegenerative research, hydroxymethylation studies are rare, particularly genome-wide mapping studies. As an initial study to analyze 5-hydroxymethylcytosine (5-hmC) in the Alzheimer’s disease (AD) genome, reduced representation hydroxymethylation profiling (RRHP) was used to analyze more than 2 million sites of possible modification in hippocampal DNA of sporadic AD and normal control subjects. Genes with differentially hydroxymethylated regions were filtered based on previously published microarray data for altered gene expression in hippocampal DNA of AD subjects. Our data show significant pathways for altered levels of 5-hmC in the hippocampus of AD subjects compared to age-matched normal controls involved in signaling, energy metabolism, cell function, gene expression, protein degradation, and cell structure and stabilization. Overall, our data suggest a possible role for the dysregulation of epigenetic modifications to cytosine in late stage AD.