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Sequencing of methylase-accessible regions in integral circular extrachromosomal DNA reveals differences in chromatin structure

BACKGROUND: Although extrachromosomal DNA (ecDNA) has been intensively studied for several decades, the mechanisms underlying its tumorigenic effects have been revealed only recently. In most conventional sequencing studies, the high-throughput short-read sequencing largely ignores the epigenetic st...

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Autores principales: Chen, Weitian, Weng, Zhe, Xie, Zhe, Xie, Yeming, Zhang, Chen, Chen, Zhichao, Ruan, Fengying, Wang, Juan, Sun, Yuxin, Fang, Yitong, Guo, Mei, Tong, Yiqin, Li, Yaning, Tang, Chong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383416/
https://www.ncbi.nlm.nih.gov/pubmed/34425889
http://dx.doi.org/10.1186/s13072-021-00416-5
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author Chen, Weitian
Weng, Zhe
Xie, Zhe
Xie, Yeming
Zhang, Chen
Chen, Zhichao
Ruan, Fengying
Wang, Juan
Sun, Yuxin
Fang, Yitong
Guo, Mei
Tong, Yiqin
Li, Yaning
Tang, Chong
author_facet Chen, Weitian
Weng, Zhe
Xie, Zhe
Xie, Yeming
Zhang, Chen
Chen, Zhichao
Ruan, Fengying
Wang, Juan
Sun, Yuxin
Fang, Yitong
Guo, Mei
Tong, Yiqin
Li, Yaning
Tang, Chong
author_sort Chen, Weitian
collection PubMed
description BACKGROUND: Although extrachromosomal DNA (ecDNA) has been intensively studied for several decades, the mechanisms underlying its tumorigenic effects have been revealed only recently. In most conventional sequencing studies, the high-throughput short-read sequencing largely ignores the epigenetic status of most ecDNA regions except for the junctional areas. METHODS: Here, we developed a method of sequencing enzyme-accessible chromatin in circular DNA (CCDA-seq) based on the use of methylase to label open chromatin without fragmentation and exonuclease to enrich ecDNA sequencing depth, followed by long-read nanopore sequencing. RESULTS: Using CCDA-seq, we observed significantly different patterns in nucleosome/regulator binding to ecDNA at a single-molecule resolution. CONCLUSIONS: These results deepen the understanding of ecDNA regulatory mechanisms. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13072-021-00416-5.
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spelling pubmed-83834162021-08-25 Sequencing of methylase-accessible regions in integral circular extrachromosomal DNA reveals differences in chromatin structure Chen, Weitian Weng, Zhe Xie, Zhe Xie, Yeming Zhang, Chen Chen, Zhichao Ruan, Fengying Wang, Juan Sun, Yuxin Fang, Yitong Guo, Mei Tong, Yiqin Li, Yaning Tang, Chong Epigenetics Chromatin Research BACKGROUND: Although extrachromosomal DNA (ecDNA) has been intensively studied for several decades, the mechanisms underlying its tumorigenic effects have been revealed only recently. In most conventional sequencing studies, the high-throughput short-read sequencing largely ignores the epigenetic status of most ecDNA regions except for the junctional areas. METHODS: Here, we developed a method of sequencing enzyme-accessible chromatin in circular DNA (CCDA-seq) based on the use of methylase to label open chromatin without fragmentation and exonuclease to enrich ecDNA sequencing depth, followed by long-read nanopore sequencing. RESULTS: Using CCDA-seq, we observed significantly different patterns in nucleosome/regulator binding to ecDNA at a single-molecule resolution. CONCLUSIONS: These results deepen the understanding of ecDNA regulatory mechanisms. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13072-021-00416-5. BioMed Central 2021-08-23 /pmc/articles/PMC8383416/ /pubmed/34425889 http://dx.doi.org/10.1186/s13072-021-00416-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Chen, Weitian
Weng, Zhe
Xie, Zhe
Xie, Yeming
Zhang, Chen
Chen, Zhichao
Ruan, Fengying
Wang, Juan
Sun, Yuxin
Fang, Yitong
Guo, Mei
Tong, Yiqin
Li, Yaning
Tang, Chong
Sequencing of methylase-accessible regions in integral circular extrachromosomal DNA reveals differences in chromatin structure
title Sequencing of methylase-accessible regions in integral circular extrachromosomal DNA reveals differences in chromatin structure
title_full Sequencing of methylase-accessible regions in integral circular extrachromosomal DNA reveals differences in chromatin structure
title_fullStr Sequencing of methylase-accessible regions in integral circular extrachromosomal DNA reveals differences in chromatin structure
title_full_unstemmed Sequencing of methylase-accessible regions in integral circular extrachromosomal DNA reveals differences in chromatin structure
title_short Sequencing of methylase-accessible regions in integral circular extrachromosomal DNA reveals differences in chromatin structure
title_sort sequencing of methylase-accessible regions in integral circular extrachromosomal dna reveals differences in chromatin structure
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8383416/
https://www.ncbi.nlm.nih.gov/pubmed/34425889
http://dx.doi.org/10.1186/s13072-021-00416-5
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