Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to induce chromatin opening

Abstract Type II DNA topoisomerases (topo II) flip the spatial positions of two DNA duplexes, called G- and T- segments, by a cleavage-passage-resealing mechanism. In living cells, these DNA segments can be derived from distant sites on the same chromosome. Due to lack of proper methodology, however...

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Autores principales:	Mary Miyaji, Ryohei Furuta, Osamu Hosoya, Kuniaki Sano, Norikazu Hara, Ryozo Kuwano, Jiyoung Kang, Masaru Tateno, Kimiko M. Tsutsui, Ken Tsutsui
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5291d081cd5a40e69f1221a370ac306d
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spelling	oai:doaj.org-article:5291d081cd5a40e69f1221a370ac306d2021-12-02T15:10:30ZTopoisomerase IIβ targets DNA crossovers formed between distant homologous sites to induce chromatin opening10.1038/s41598-020-75004-w2045-2322https://doaj.org/article/5291d081cd5a40e69f1221a370ac306d2020-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-75004-whttps://doaj.org/toc/2045-2322Abstract Type II DNA topoisomerases (topo II) flip the spatial positions of two DNA duplexes, called G- and T- segments, by a cleavage-passage-resealing mechanism. In living cells, these DNA segments can be derived from distant sites on the same chromosome. Due to lack of proper methodology, however, no direct evidence has been described so far. The beta isoform of topo II (topo IIβ) is essential for transcriptional regulation of genes expressed in the final stage of neuronal differentiation. Here we devise a genome-wide mapping technique (eTIP-seq) for topo IIβ target sites that can measure the genomic distance between G- and T-segments. It revealed that the enzyme operates in two distinctive modes, termed proximal strand passage (PSP) and distal strand passage (DSP). PSP sites are concentrated around transcription start sites, whereas DSP sites are heavily clustered in small number of hotspots. While PSP represent the conventional topo II targets that remove local torsional stresses, DSP sites have not been described previously. Most remarkably, DSP is driven by the pairing between homologous sequences or repeats located in a large distance. A model-building approach suggested that topo IIβ acts on crossovers to unknot the intertwined DSP sites, leading to chromatin decondensation.Mary MiyajiRyohei FurutaOsamu HosoyaKuniaki SanoNorikazu HaraRyozo KuwanoJiyoung KangMasaru TatenoKimiko M. TsutsuiKen TsutsuiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-14 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mary Miyaji Ryohei Furuta Osamu Hosoya Kuniaki Sano Norikazu Hara Ryozo Kuwano Jiyoung Kang Masaru Tateno Kimiko M. Tsutsui Ken Tsutsui Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to induce chromatin opening
description	Abstract Type II DNA topoisomerases (topo II) flip the spatial positions of two DNA duplexes, called G- and T- segments, by a cleavage-passage-resealing mechanism. In living cells, these DNA segments can be derived from distant sites on the same chromosome. Due to lack of proper methodology, however, no direct evidence has been described so far. The beta isoform of topo II (topo IIβ) is essential for transcriptional regulation of genes expressed in the final stage of neuronal differentiation. Here we devise a genome-wide mapping technique (eTIP-seq) for topo IIβ target sites that can measure the genomic distance between G- and T-segments. It revealed that the enzyme operates in two distinctive modes, termed proximal strand passage (PSP) and distal strand passage (DSP). PSP sites are concentrated around transcription start sites, whereas DSP sites are heavily clustered in small number of hotspots. While PSP represent the conventional topo II targets that remove local torsional stresses, DSP sites have not been described previously. Most remarkably, DSP is driven by the pairing between homologous sequences or repeats located in a large distance. A model-building approach suggested that topo IIβ acts on crossovers to unknot the intertwined DSP sites, leading to chromatin decondensation.
format	article
author	Mary Miyaji Ryohei Furuta Osamu Hosoya Kuniaki Sano Norikazu Hara Ryozo Kuwano Jiyoung Kang Masaru Tateno Kimiko M. Tsutsui Ken Tsutsui
author_facet	Mary Miyaji Ryohei Furuta Osamu Hosoya Kuniaki Sano Norikazu Hara Ryozo Kuwano Jiyoung Kang Masaru Tateno Kimiko M. Tsutsui Ken Tsutsui
author_sort	Mary Miyaji
title	Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to induce chromatin opening
title_short	Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to induce chromatin opening
title_full	Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to induce chromatin opening
title_fullStr	Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to induce chromatin opening
title_full_unstemmed	Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to induce chromatin opening
title_sort	topoisomerase iiβ targets dna crossovers formed between distant homologous sites to induce chromatin opening
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/5291d081cd5a40e69f1221a370ac306d
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Topoisomerase IIβ targets DNA crossovers formed between distant homologous sites to induce chromatin opening

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