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


ABSTRACT:

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.

SUBMITTER: Chen W 

PROVIDER: S-EPMC8383416 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Chen Weitian W   Weng Zhe Z   Xie Zhe Z   Xie Yeming Y   Zhang Chen C   Chen Zhichao Z   Ruan Fengying F   Wang Juan J   Sun Yuxin Y   Fang Yitong Y   Guo Mei M   Tong Yiqin Y   Li Yaning Y   Tang Chong C  

Epigenetics & chromatin 20210823 1


<h4>Background</h4>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.<h4>Methods</h4>Here, we developed a method of sequencing enzyme-accessible chromatin in circular DNA (CCDA-seq) based on the use of m  ...[more]

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