Orthosilicic acid, ascorbate (Vitamin C), and polyphenols are bioactive compounds that influence gene expression by modulating epigenetic mechanisms, specifically DNA methylation and histone methylation pathways. They act as cofactors or inhibitors for enzymes that add or remove methyl groups, thereby altering chromatin structure and, consequently, gene silencing or activation.
Modulation of DNA methylation and histone acetylation via DNMT1 and HDAC inhibition is a key mechanism through which dietary components—specifically polyphenols and sugar-acids—exercise chemopreventive and health-promoting effects. These compounds act as natural epigenetic agents that can reverse aberrant gene silencing (such as in cancer) by inhibiting the enzymes that methylate DNA and deacetylate histones.
Thymoquinone (TQ), a compound in black seed oil, acts as a potent epigenetic modulator by inhibiting DNA methyltransferase 1 (DNMT1), which reduces methylation and suppresses cancer cell proliferation. It downregulates UHRF1, reducing DNMT1 activity and promoting tumor suppressor gene reactivation. While ascorbate (vitamin C) is known for increasing DNA demethylation via TET enzymes, TQ specifically targets DNMT1 to reverse epigenetic silencing in various cancers.
Orthosilicic Acid (OSA) and Methylation
Research, including studies on HaCaT cells, suggests that dietary silicon in the form of orthosilicic acid (OSA) may cause significant changes in genome-wide DNA methylation.
The relationship indicates that nutritional factors like OSA may interact with the epigenetic machinery (DNA/histone methylation pathways).
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Molecular Interactions and Binding
Positive Polarity Interaction: The nucleosome core particle is stabilized by electrostatic interactions between the negatively charged DNA phosphate backbone and positively charged amino acid residues (like lysine and arginine) on histone tails.
Methylation Effect: Methylation of lysine residues changes the biophysical properties of these tails, often acting as a docking platform for "reader" proteins (HP1 binding to H3K9me3), which can further pack the chromatin into a closed, inactive configuration.
Functional Significance
These pathways are crucial for maintaining heterochromatin, silencing transposable elements, regulating imprinting, and defining cell-type-specific gene expression. Dysregulation of these mechanisms is directly linked to cancer, as abnormal methylation patterns can silence tumor suppressor genes.
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Examples: Common HDAC inhibitors include vorinostat, panobinostat, and valproic acid.