title: Chiral Antioxidant-based Gold Nanoclusters Reprogram DNA Epigenetic Patterns.
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.
authors.affiliation: Institute of Nano Biomedicine and Engineering, Shanghai Engineering Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Nano Biomedicine and Engineering, Shanghai Engineering Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.|National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
authors.forename: Hualin
authors.initials: H
authors.lastname: Fu
authors.affiliation: Institute of Nano Biomedicine and Engineering, Shanghai Engineering Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Chunlei
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Nano Biomedicine and Engineering, Shanghai Engineering Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Shangli
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Institute of Nano Biomedicine and Engineering, Shanghai Engineering Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.|School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Institute of Nano Biomedicine and Engineering, Shanghai Engineering Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.|Department of Experimental Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Institute of Nano Biomedicine and Engineering, Shanghai Engineering Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.|National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
authors.forename: Weilin
authors.initials: W
authors.lastname: Jin
authors.affiliation: Massachusetts Institute of Technology, Institute for Medical Engineering and Science, Harvard-MIT Division for Health Sciences and Technology, Cambridge, Massachusetts, USA.|School of Engineering and Materials Science, Queen Mary University of London, London, UK.
authors.forename: João
authors.initials: J
authors.lastname: Conde
authors.affiliation: Institute of Nano Biomedicine and Engineering, Shanghai Engineering Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, Key Lab. for Thin Film and Microfabrication Technology of Ministry of Education, School of Electronic Information and Electronic Engineering, Shanghai Jiao Tong University, Shanghai 200240, China.|National Center for Translational Medicine, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China.
authors.forename: Daxiang
authors.initials: D
authors.lastname: Cui
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives / Q000378:metabolism; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D055162:Biocatalysis; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005978:Glutathione / Q000737:chemistry; D006046:Gold / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism; D013237:Stereoisomerism
chemical_list: D000975:Antioxidants; D004268:DNA-Binding Proteins; D017382:Reactive Oxygen Species; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D006046:Gold; D004247:DNA; D005978:Glutathione