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Topoisomerase II inhibition involves characteristic chromosomal expression patterns

BACKGROUND: The phenomenon of co-localization of transcriptionally upregulated genes showing similar expression levels is known across all eukaryotic genomes. We recently mapped the Aroclor 1254-regulated transcriptome back onto the genome and provided evidence for the statistically significant co-l...

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Autores principales: Reymann, Susanne, Borlak, Jürgen
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2488358/
https://www.ncbi.nlm.nih.gov/pubmed/18611269
http://dx.doi.org/10.1186/1471-2164-9-324
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author Reymann, Susanne
Borlak, Jürgen
author_facet Reymann, Susanne
Borlak, Jürgen
author_sort Reymann, Susanne
collection PubMed
description BACKGROUND: The phenomenon of co-localization of transcriptionally upregulated genes showing similar expression levels is known across all eukaryotic genomes. We recently mapped the Aroclor 1254-regulated transcriptome back onto the genome and provided evidence for the statistically significant co-localization of regulated genes. They did, however, not always show similar expression levels, and many of the regulated genes were, in fact, repressed. RESULTS: In this study, we were able to reproduce this observation with microarray data stemming from 1) human hepatocytes treated with the gyrase and potential topoisomerase II inhibitor trovafloxacin, 2) human hepatocytes treated with the topoisomerase II inhibitor doxorubicin and 3) mouse lymphoma cells treated with the topoisomerase II inhibitor etoposide. We found statistically significant co-localization of regulated gene pairs – induced and repressed – within the window size of 0–100 kbp. Notably, by using microarray data stemming from lung tissue of a mouse transgenic line overexpressing the transcription factor c-myc, which served as a negative control, we found regulated genes to be located with regard to each other nearly in the same way as genes distributed randomly all over the genome (0–100 kbp). CONCLUSION: We suggest topoisomerase II inhibition by Aroclor 1254, trovafloxacin, doxorubicin, and etoposide to be responsible for significant co-localization of regulated genes through the inability of the stabilized enzyme complexes to religate DNA. Within the permanently opened chromatin domains, neighbored genes might be allowed to be regulated. Overexpression of c-myc, however, does not inhibit topoisomerase II activity. Consequently, the enzyme is able to perform its normal function of transiently breaking and rejoining the DNA double strand. As a result, exclusively target genes are regulated.
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spelling pubmed-24883582008-07-29 Topoisomerase II inhibition involves characteristic chromosomal expression patterns Reymann, Susanne Borlak, Jürgen BMC Genomics Research Article BACKGROUND: The phenomenon of co-localization of transcriptionally upregulated genes showing similar expression levels is known across all eukaryotic genomes. We recently mapped the Aroclor 1254-regulated transcriptome back onto the genome and provided evidence for the statistically significant co-localization of regulated genes. They did, however, not always show similar expression levels, and many of the regulated genes were, in fact, repressed. RESULTS: In this study, we were able to reproduce this observation with microarray data stemming from 1) human hepatocytes treated with the gyrase and potential topoisomerase II inhibitor trovafloxacin, 2) human hepatocytes treated with the topoisomerase II inhibitor doxorubicin and 3) mouse lymphoma cells treated with the topoisomerase II inhibitor etoposide. We found statistically significant co-localization of regulated gene pairs – induced and repressed – within the window size of 0–100 kbp. Notably, by using microarray data stemming from lung tissue of a mouse transgenic line overexpressing the transcription factor c-myc, which served as a negative control, we found regulated genes to be located with regard to each other nearly in the same way as genes distributed randomly all over the genome (0–100 kbp). CONCLUSION: We suggest topoisomerase II inhibition by Aroclor 1254, trovafloxacin, doxorubicin, and etoposide to be responsible for significant co-localization of regulated genes through the inability of the stabilized enzyme complexes to religate DNA. Within the permanently opened chromatin domains, neighbored genes might be allowed to be regulated. Overexpression of c-myc, however, does not inhibit topoisomerase II activity. Consequently, the enzyme is able to perform its normal function of transiently breaking and rejoining the DNA double strand. As a result, exclusively target genes are regulated. BioMed Central 2008-07-08 /pmc/articles/PMC2488358/ /pubmed/18611269 http://dx.doi.org/10.1186/1471-2164-9-324 Text en Copyright © 2008 Reymann and Borlak; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Reymann, Susanne
Borlak, Jürgen
Topoisomerase II inhibition involves characteristic chromosomal expression patterns
title Topoisomerase II inhibition involves characteristic chromosomal expression patterns
title_full Topoisomerase II inhibition involves characteristic chromosomal expression patterns
title_fullStr Topoisomerase II inhibition involves characteristic chromosomal expression patterns
title_full_unstemmed Topoisomerase II inhibition involves characteristic chromosomal expression patterns
title_short Topoisomerase II inhibition involves characteristic chromosomal expression patterns
title_sort topoisomerase ii inhibition involves characteristic chromosomal expression patterns
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2488358/
https://www.ncbi.nlm.nih.gov/pubmed/18611269
http://dx.doi.org/10.1186/1471-2164-9-324
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