title: Multiplexed Detection of Epigenetic Markers Using Quantum Dot (QD)-Encoded Hydrogel Microparticles.
abstract: Epigenetic alterations in gene expression are influenced by experiences and environment, resulting in significant variation of epigenetic markers from individual to individual. Therefore, it is imperative to measure various epigenetic markers simultaneously from samples of individual subjects to accurately analyze the epigenetic markers in biological samples. Moreover, the individualized genome-wide analysis has become a critical technology for recent trends in clinical applications such as early diagnosis and personalized medicine screening of numerous diseases. The array-based detection of modified histones, conventionally used for multiplexed analysis of epigenetic changes, requires pooling of samples from many subjects to analyze population-wise differences in the expression of histone markers and does not permit individualized analysis. Here, we report multiplexed detection of genome-wide changes in various histone modifications at a single-residue resolution using quantum dot (QD)-encoded polyethylene glycol diacrylate (PEGDA) hydrogel microparticles. To demonstrate the potential of our methodology, we present the simultaneous detection of (1) acetylation of lysine 9 of histone 3 (Ac-H3K9), (2) dimethylation of H3K9 (2Me-H3K9), and (3) trimethylation of H3K9 (3Me-H3K9) from three distinct regions in the brain [nucleus accumbens (NAc), dorsal striatum (DSt), and cerebellum (Cbl)] of cocaine-exposed mice. Our hydrogel-based epigenetic assay enabled relative quantification of the three histone variants from only 10 μL of each brain lysate (protein content = ∼ 1 μg/μL) per mouse. We verified that the exposure to cocaine induced a significant increase of acetylation while a notable decrease in methylation in NAc.
authors.affiliation: Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.|Department of Chemical and Biological Engineering, Korea University , Seoul 02841, Korea.
authors.forename: Sang Yun
authors.initials: SY
authors.lastname: Yeom
authors.affiliation: Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.
authors.forename: Choong Hyun
authors.initials: CH
authors.lastname: Son
authors.affiliation: Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.|Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.|Department of Neuroscience, Korea University of Science and Technology (UST) , Daejeon 34113, Korea.
authors.forename: Byung Sun
authors.initials: BS
authors.lastname: Kim
authors.affiliation: Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.|Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.
authors.forename: Sung Hyun
authors.initials: SH
authors.lastname: Tag
authors.affiliation: Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.
authors.forename: Eunjoo
authors.initials: E
authors.lastname: Nam
authors.affiliation: Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST) , Daejeon 34113, Korea.
authors.forename: Hyogeun
authors.initials: H
authors.lastname: Shin
authors.affiliation: Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.
authors.forename: So Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.
authors.forename: Haemin
authors.initials: H
authors.lastname: Gang
authors.affiliation: Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST) , Daejeon 34113, Korea.
authors.forename: Hyunjoo J
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Chemical and Biological Engineering, Korea University , Seoul 02841, Korea.|Green School, Korea University , Seoul 02841, Korea.
authors.forename: Jungkyu
authors.initials: J
authors.lastname: Choi
authors.affiliation: Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.|Center for Neuroscience, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.|Department of Neuroscience, Korea University of Science and Technology (UST) , Daejeon 34113, Korea.
authors.forename: Heh-In
authors.initials: HI
authors.lastname: Im
authors.affiliation: Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST) , Daejeon 34113, Korea.
authors.forename: Il-Joo
authors.initials: IJ
authors.lastname: Cho
authors.affiliation: Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST) , Seoul 02792, Korea.|Department of Biomedical Engineering, Korea University of Science and Technology (UST) , Daejeon 34113, Korea.
authors.forename: Nakwon
authors.initials: N
authors.lastname: Choi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002478:Cells, Cultured; D044127:Epigenesis, Genetic / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D045663:Quantum Dots; D013499:Surface Properties
chemical_list: D015415:Biomarkers; C437167:poly(ethylene glycol)diacrylate; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols