Two-color fluorescent cytosine extension assay for the determination of global DNA methylation

Here, we present a DNA restriction enzyme–based, fluorescent cytosine extension assay (CEA) to improve normalization and technical variation among sample-to-sample measurements. The assay includes end-labeling of parallel methylation-sensitive and methylation-insensitive DNA restriction enzyme diges...

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Main Authors: Gu Zhou, Craig Parfett, Cathy Cummings-Lorbetskie, Gong-Hua Xiao, Daniel Desaulniers
Format: Article
Language:English
Published: Taylor & Francis Group 2017-04-01
Series:BioTechniques
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Online Access:https://www.future-science.com/doi/10.2144/000114533
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author Gu Zhou
Craig Parfett
Cathy Cummings-Lorbetskie
Gong-Hua Xiao
Daniel Desaulniers
author_facet Gu Zhou
Craig Parfett
Cathy Cummings-Lorbetskie
Gong-Hua Xiao
Daniel Desaulniers
author_sort Gu Zhou
collection DOAJ
description Here, we present a DNA restriction enzyme–based, fluorescent cytosine extension assay (CEA) to improve normalization and technical variation among sample-to-sample measurements. The assay includes end-labeling of parallel methylation-sensitive and methylation-insensitive DNA restriction enzyme digests along with co-purification and subsequent co-measurement of incorporated fluorescence. This non-radioactive, two-color fluorescent CEA (TCF-CEA) was shown to be a relatively rapid and accurate, with 3-fold greater precision than the one-color CEA. In addition, TCF-CEA provided an index of global DNA methylation that was sensitive to differences >5%. TCF-CEA results were highly correlated with LUminometric Methylation Assay (LUMA) results using human liver cell lines (HepG2, HepaRG, HC-04) as well as a human liver primary cell culture. Hypomethylation was observed in cells treated with the de-methylating agent 5-aza-2'-deoxycytidine. These results demonstrate that TCF-CEA provides a simple method for measuring relative degrees of global DNA methylation that could potentially be scaled up to higher-throughput formats.
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spelling doaj-art-c6d6f80b91ab4edc8eefb5efe2ddd1ab2025-08-20T02:26:03ZengTaylor & Francis GroupBioTechniques0736-62051940-98182017-04-0162415716410.2144/000114533Two-color fluorescent cytosine extension assay for the determination of global DNA methylationGu Zhou0Craig Parfett1Cathy Cummings-Lorbetskie2Gong-Hua Xiao3Daniel Desaulniers41Mechanistic Studies Division, Environmental Health Science and Research Bureau, HECSB, Health Canada, Ottawa, Canada1Mechanistic Studies Division, Environmental Health Science and Research Bureau, HECSB, Health Canada, Ottawa, Canada2Hazard Identification Division, Environmental Health Science and Research Bureau HECSB, Health Canada, Ottawa, Canada2Hazard Identification Division, Environmental Health Science and Research Bureau HECSB, Health Canada, Ottawa, Canada2Hazard Identification Division, Environmental Health Science and Research Bureau HECSB, Health Canada, Ottawa, CanadaHere, we present a DNA restriction enzyme–based, fluorescent cytosine extension assay (CEA) to improve normalization and technical variation among sample-to-sample measurements. The assay includes end-labeling of parallel methylation-sensitive and methylation-insensitive DNA restriction enzyme digests along with co-purification and subsequent co-measurement of incorporated fluorescence. This non-radioactive, two-color fluorescent CEA (TCF-CEA) was shown to be a relatively rapid and accurate, with 3-fold greater precision than the one-color CEA. In addition, TCF-CEA provided an index of global DNA methylation that was sensitive to differences >5%. TCF-CEA results were highly correlated with LUminometric Methylation Assay (LUMA) results using human liver cell lines (HepG2, HepaRG, HC-04) as well as a human liver primary cell culture. Hypomethylation was observed in cells treated with the de-methylating agent 5-aza-2'-deoxycytidine. These results demonstrate that TCF-CEA provides a simple method for measuring relative degrees of global DNA methylation that could potentially be scaled up to higher-throughput formats.https://www.future-science.com/doi/10.2144/000114533methylation sensitive restriction enzymedual labelaccuracyprecision
spellingShingle Gu Zhou
Craig Parfett
Cathy Cummings-Lorbetskie
Gong-Hua Xiao
Daniel Desaulniers
Two-color fluorescent cytosine extension assay for the determination of global DNA methylation
BioTechniques
methylation sensitive restriction enzyme
dual label
accuracy
precision
title Two-color fluorescent cytosine extension assay for the determination of global DNA methylation
title_full Two-color fluorescent cytosine extension assay for the determination of global DNA methylation
title_fullStr Two-color fluorescent cytosine extension assay for the determination of global DNA methylation
title_full_unstemmed Two-color fluorescent cytosine extension assay for the determination of global DNA methylation
title_short Two-color fluorescent cytosine extension assay for the determination of global DNA methylation
title_sort two color fluorescent cytosine extension assay for the determination of global dna methylation
topic methylation sensitive restriction enzyme
dual label
accuracy
precision
url https://www.future-science.com/doi/10.2144/000114533
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