Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period

The Bmal1 gene is essential for the circadian system, and its promoter has a unique open chromatin structure. We examined the mechanism of topoisomerase I (Top1) to understand the role of the unique chromatin structure in Bmal1 gene regulation. Camptothecin, a Top1 inhibitor, and Top1 small interfer...

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Main Authors:	Onishi, Yoshiaki, Kawano, Yasuhiro
Format:	Online
Language:	English
Published:	Oxford University Press 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479213/

id	pubmed-3479213
recordtype	oai_dc
spelling	pubmed-34792132012-10-24 Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period Onishi, Yoshiaki Kawano, Yasuhiro Gene Regulation, Chromatin and Epigenetics The Bmal1 gene is essential for the circadian system, and its promoter has a unique open chromatin structure. We examined the mechanism of topoisomerase I (Top1) to understand the role of the unique chromatin structure in Bmal1 gene regulation. Camptothecin, a Top1 inhibitor, and Top1 small interfering RNA (siRNA) enhanced Baml1 transcription and lengthened its circadian period. Top1 is located at an intermediate region between two ROREs that are critical cis-elements of circadian transcription and the profile of Top1 binding indicated anti-phase circadian oscillation of Bmal1 transcription. Promoter assays showed that the Top1-binding site is required for transcriptional suppression and that it functions cooperatively with the distal RORE, supporting that Bmal1 transcription is upregulated by Top1 inhibition. A DNA fragment between the ROREs, where the Top1-binding site is located, behaved like a right-handed superhelical twist, and modulation of Top1 activity by camptothecin and Top1 siRNA altered the footprint profile, indicating modulation of the chromatin structure. These data indicate that Top1 modulates the chromatin structure of the Bmal1 promoter, regulates Bmal1 transcription and influences the circadian period. Oxford University Press 2012-10 2012-08-13 /pmc/articles/PMC3479213/ /pubmed/22904072 http://dx.doi.org/10.1093/nar/gks779 Text en © The Author(s) 2012. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Onishi, Yoshiaki Kawano, Yasuhiro
spellingShingle	Onishi, Yoshiaki Kawano, Yasuhiro Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period
author_facet	Onishi, Yoshiaki Kawano, Yasuhiro
author_sort	Onishi, Yoshiaki
title	Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period
title_short	Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period
title_full	Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period
title_fullStr	Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period
title_full_unstemmed	Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period
title_sort	rhythmic binding of topoisomerase i impacts on the transcription of bmal1 and circadian period
description	The Bmal1 gene is essential for the circadian system, and its promoter has a unique open chromatin structure. We examined the mechanism of topoisomerase I (Top1) to understand the role of the unique chromatin structure in Bmal1 gene regulation. Camptothecin, a Top1 inhibitor, and Top1 small interfering RNA (siRNA) enhanced Baml1 transcription and lengthened its circadian period. Top1 is located at an intermediate region between two ROREs that are critical cis-elements of circadian transcription and the profile of Top1 binding indicated anti-phase circadian oscillation of Bmal1 transcription. Promoter assays showed that the Top1-binding site is required for transcriptional suppression and that it functions cooperatively with the distal RORE, supporting that Bmal1 transcription is upregulated by Top1 inhibition. A DNA fragment between the ROREs, where the Top1-binding site is located, behaved like a right-handed superhelical twist, and modulation of Top1 activity by camptothecin and Top1 siRNA altered the footprint profile, indicating modulation of the chromatin structure. These data indicate that Top1 modulates the chromatin structure of the Bmal1 promoter, regulates Bmal1 transcription and influences the circadian period.
publisher	Oxford University Press
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3479213/
_version_	1611918315960139776

Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1 and circadian period

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