Abstract
ABSTRACTIn this study, we developed an experimental protocol leveraging enhanced reduced representation bisulphite sequencing to investigate methylation and gene expression patterns in the hippocampus in response to polyphenolic compounds. We report that the administration of a standardized bioavailable polyphenolic preparation (BDPP) differentially influences methylated cytosine patterns in introns, UTR and exons in hippocampal genes. We subsequently established that dietary BDPP-mediated changes in methylation influenced the transcriptional pattern of select genes that are involved in synaptic plasticity. In addition, we showed dietary BDPP mediated changes in the transcriptional pattern of genes associated with epigenetic modifications, including members of the DNA methyl transferase family (DNMTs) and the Ten-eleven translocation methylcytosine dioxygenases family (TETs). We then identified the specific brain bioavailable polyphenols effective in regulating the transcription of DNMTs, TETs and a subset of differentially methylated synaptic plasticity-associated genes. The study implicates the regulation of gene expression in the hippocampus by epigenetic mechanisms as a novel therapeutic target for dietary polyphenols.
Highlights
IntroductionThe methylation status of cytosine residues in DNA are dependent upon the activity of epigenetic modifiers, such as by DNA methyl transferases (DNMTs) or Ten-eleven translocation
Epigenetic modifications of the genome are a critical mechanism that controls the expression and types of genes transcribed from DNA
BDPP-treatment influences the expression of methylationrelated epigenetic modifying genes In order to test whether dietary BDPP can contribute to synaptic plasticity through epigenetic mechanisms, C57BL6 mice were randomly grouped into two groups: vehicle treated and BDPP treated (BDPP)
Summary
The methylation status of cytosine residues in DNA are dependent upon the activity of epigenetic modifiers, such as by DNA methyl transferases (DNMTs) or Ten-eleven translocation. Received 23 April 2018; Accepted 20 June 2018 methylcytosine dioxygenases (TETs). These epigenetic modifications are known to regulate gene expression in a region specific manner. Evidence to date has yet to establish a consistent relationship between the methylation of intronic, exonic, or untranslated regions (UTR) and the expression pattern of the gene’s corresponding proteins
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