Chiral Antioxidant-based Gold Nanoclusters Reprogram DNA Epigenetic Patterns.

Yue Ma,João Conde,Chunlei Zhang,Hualin Fu,Shangli Cheng,Weilin Jin,Zhen Wang,Daxiang Cui,Jie Gao

doi:10.1038/srep33436

Abstract

Epigenetic modifications sit ‘on top of’ the genome and influence DNA transcription, which can force a significant impact on cellular behavior and phenotype and, consequently human development and disease. Conventional methods for evaluating epigenetic modifications have inherent limitations and, hence, new methods based on nanoscale devices are needed. Here, we found that antioxidant (glutathione) chiral gold nanoclusters induce a decrease of 5-hydroxymethylcytosine (5hmC), which is an important epigenetic marker that associates with gene transcription regulation. This epigenetic change was triggered partially through ROS activation and oxidation generated by the treatment with glutathione chiral gold nanoclusters, which may inhibit the activity of TET proteins catalyzing the conversion of 5-methylcytosine (5mC) to 5hmC. In addition, these chiral gold nanoclusters can downregulate TET1 and TET2 mRNA expression. Alteration of TET-5hmC signaling will then affect several downstream targets and be involved in many aspects of cell behavior. We demonstrate for the first time that antioxidant-based chiral gold nanomaterials have a direct effect on epigenetic process of TET-5hmC pathways and reveal critical DNA demethylation patterns.

Highlights

The MIT Faculty has made this article openly available
These antioxidant-based chiral AuNCs can down-regulate the mRNA expression level of TET1 and TET2, and induce the aggregations of ten-eleven translocation (TET) proteins through oxidation of their catalytic domains. These alterations can result in the decreasing of the catalytic activities of TET proteins and the subsequent global decline of 5hmC levels, which leads to gene expression changes that are involved in cell adhesion, migration, proliferation, differentiation and cell apoptosis
We found that the non-cytotoxic AuNCs@L-GSH can down-regulate the mRNA expression level of TET1 and TET2, and induce the aggregations of TET proteins through oxidation of their catalytic domains

Summary

Nanoclusters Reprogram DNA

Epigenetic Patterns received: 13 April 2016 accepted: 26 August 2016 Published: 16 September 2016. These antioxidant-based chiral AuNCs can down-regulate the mRNA expression level of TET1 and TET2, and induce the aggregations of TET proteins through oxidation of their catalytic domains These alterations can result in the decreasing of the catalytic activities of TET proteins and the subsequent global decline of 5hmC levels, which leads to gene expression changes that are involved in cell adhesion, migration, proliferation, differentiation and cell apoptosis. This demethylation process is necessary for epigenetic reprogramming of genes and is directly involved in many important disease mechanisms such as tumor progression. We prove that 5hmC serves both as an intermediate of DNA demethylation as well as a stable epigenetic marker

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