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Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
Oregonin from Alnus incana bark affects DNA methyltransferases expression and mitochondrial DNA copies in mouse
Jelena Krasilnikova1, Liga Lauberte2, Elena Stoyanova3
1a Department of Biochemistry , Stradiņš University , Riga , Latvia.
Abstract:
Oregonin is an open-chain diarylheptanoid isolated from Alnus incana bark that possesses remarkable antioxidant and anti-inflammatory properties, inhibits adipogenesis, and can be used in the prevention of obesity and related metabolic disorders. Here, we aimed to investigate the effects of oregonin on the epigenetic regulation in cells as well as its ability to modulate DNA methylating enzymes expression and mitochondrial DNA (mtDNA) copies. Our results show that oregonin altered the expression of DNA methyltransferases and mtDNA copy numbers in dependency on concentration and specificity of cells genotype. A close correlation between mtDNA copy numbers and mRNA expression of the mtDnmt1 and Dnmt3b was established. Moreover, molecular modeling suggested that oregonin fits the catalytic site of DNMT1 and partially overlaps with binding of the cofactor. These findings further extend the knowledge on oregonin, and elucidate for the first time its potential to affect the key players of the DNA methylation process, namely DNMTs transcripts and mtDNA.
Insights
Oregonin, a compound from Alnus incana bark, impacts epigenetic regulation by altering DNA methyltransferases and mitochondrial DNA (mtDNA) copy numbers. This suggests a novel mechanism for its therapeutic potential in metabolic disorders.
Area of Science:
- Biochemistry
- Epigenetics
- Molecular Biology
Background:
- Oregonin, an open-chain diarylheptanoid from Alnus incana bark, exhibits antioxidant, anti-inflammatory, and anti-adipogenic properties.
- It shows potential in preventing obesity and related metabolic disorders.
- The precise epigenetic mechanisms underlying oregonin's effects are not fully understood.
Purpose of the Study:
- To investigate the effects of oregonin on epigenetic regulation in cells.
- To determine oregonin's ability to modulate DNA methylating enzymes expression.
- To assess oregonin's impact on mitochondrial DNA (mtDNA) copy numbers.
Main Methods:
- Cellular assays to examine epigenetic modifications.
- Quantitative analysis of DNA methyltransferases (DNMTs) mRNA expression.
- Measurement of mitochondrial DNA (mtDNA) copy numbers.
- Molecular modeling to predict oregonin's interaction with DNMTs.
Main Results:
- Oregonin altered the expression of DNA methyltransferases (DNMTs) and mtDNA copy numbers in a concentration- and cell-type-dependent manner.
- A significant correlation was observed between mtDNA copy numbers and the mRNA expression of mtDnmt1 and Dnmt3b.
- Molecular modeling indicated that oregonin binds to the catalytic site of DNMT1, potentially interfering with cofactor binding.
Conclusions:
- Oregonin influences key players in DNA methylation, including DNMT transcripts and mtDNA.
- These findings elucidate a novel epigenetic mechanism for oregonin's biological activities.
- Oregonin's potential to modulate DNA methylation warrants further investigation for therapeutic applications in metabolic diseases.
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