Frolinger Tal, Herman Francis, Sharma Ali, Sims Steven, Wang Jun, Pasinetti Giulio Maria
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Biol Open. 2018 Oct 4;7(10):bio035196. doi: 10.1242/bio.035196.
In 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 () and the Ten-eleven translocation methylcytosine dioxygenases family (). We then identified the specific brain bioavailable polyphenols effective in regulating the transcription of , 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.
在本研究中，我们开发了一种实验方案，利用增强型简化代表性亚硫酸氢盐测序来研究海马体中响应多酚类化合物的甲基化和基因表达模式。我们报告称，给予标准化的生物可利用多酚制剂（BDPP）会对海马体基因内含子、非翻译区（UTR）和外显子中的甲基化胞嘧啶模式产生不同影响。我们随后确定，饮食中BDPP介导的甲基化变化会影响参与突触可塑性的特定基因的转录模式。此外，我们表明饮食中BDPP介导了与表观遗传修饰相关基因的转录模式变化，包括DNA甲基转移酶家族（）和10-11易位甲基胞嘧啶双加氧酶家族（）的成员。然后，我们确定了对调节、以及一部分差异甲基化的突触可塑性相关基因的转录有效的特定脑生物可利用多酚。该研究表明，通过表观遗传机制对海马体基因表达的调节作为饮食多酚的一种新型治疗靶点。
