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Clock-dependent chromatin topology modulates circadian transcription and behavior

The circadian clock in animals orchestrates widespread oscillatory gene expression programs, which underlie 24-h rhythms in behavior and physiology. Several studies have shown the possible roles of transcription factors and chromatin marks in controlling cyclic gene expression. However, how daily ac...

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Autores principales: Mermet, Jérôme, Yeung, Jake, Hurni, Clémence, Mauvoisin, Daniel, Gustafson, Kyle, Jouffe, Céline, Nicolas, Damien, Emmenegger, Yann, Gobet, Cédric, Franken, Paul, Gachon, Frédéric, Naef, Félix
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900709/
https://www.ncbi.nlm.nih.gov/pubmed/29572261
http://dx.doi.org/10.1101/gad.312397.118
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author Mermet, Jérôme
Yeung, Jake
Hurni, Clémence
Mauvoisin, Daniel
Gustafson, Kyle
Jouffe, Céline
Nicolas, Damien
Emmenegger, Yann
Gobet, Cédric
Franken, Paul
Gachon, Frédéric
Naef, Félix
author_facet Mermet, Jérôme
Yeung, Jake
Hurni, Clémence
Mauvoisin, Daniel
Gustafson, Kyle
Jouffe, Céline
Nicolas, Damien
Emmenegger, Yann
Gobet, Cédric
Franken, Paul
Gachon, Frédéric
Naef, Félix
author_sort Mermet, Jérôme
collection PubMed
description The circadian clock in animals orchestrates widespread oscillatory gene expression programs, which underlie 24-h rhythms in behavior and physiology. Several studies have shown the possible roles of transcription factors and chromatin marks in controlling cyclic gene expression. However, how daily active enhancers modulate rhythmic gene transcription in mammalian tissues is not known. Using circular chromosome conformation capture (4C) combined with sequencing (4C-seq), we discovered oscillatory promoter–enhancer interactions along the 24-h cycle in the mouse liver and kidney. Rhythms in chromatin interactions were abolished in arrhythmic Bmal1 knockout mice. Deleting a contacted intronic enhancer element in the Cryptochrome 1 (Cry1) gene was sufficient to compromise the rhythmic chromatin contacts in tissues. Moreover, the deletion reduced the daily dynamics of Cry1 transcriptional burst frequency and, remarkably, shortened the circadian period of locomotor activity rhythms. Our results establish oscillating and clock-controlled promoter–enhancer looping as a regulatory layer underlying circadian transcription and behavior.
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spelling pubmed-59007092018-05-04 Clock-dependent chromatin topology modulates circadian transcription and behavior Mermet, Jérôme Yeung, Jake Hurni, Clémence Mauvoisin, Daniel Gustafson, Kyle Jouffe, Céline Nicolas, Damien Emmenegger, Yann Gobet, Cédric Franken, Paul Gachon, Frédéric Naef, Félix Genes Dev Research Paper The circadian clock in animals orchestrates widespread oscillatory gene expression programs, which underlie 24-h rhythms in behavior and physiology. Several studies have shown the possible roles of transcription factors and chromatin marks in controlling cyclic gene expression. However, how daily active enhancers modulate rhythmic gene transcription in mammalian tissues is not known. Using circular chromosome conformation capture (4C) combined with sequencing (4C-seq), we discovered oscillatory promoter–enhancer interactions along the 24-h cycle in the mouse liver and kidney. Rhythms in chromatin interactions were abolished in arrhythmic Bmal1 knockout mice. Deleting a contacted intronic enhancer element in the Cryptochrome 1 (Cry1) gene was sufficient to compromise the rhythmic chromatin contacts in tissues. Moreover, the deletion reduced the daily dynamics of Cry1 transcriptional burst frequency and, remarkably, shortened the circadian period of locomotor activity rhythms. Our results establish oscillating and clock-controlled promoter–enhancer looping as a regulatory layer underlying circadian transcription and behavior. Cold Spring Harbor Laboratory Press 2018-03-01 /pmc/articles/PMC5900709/ /pubmed/29572261 http://dx.doi.org/10.1101/gad.312397.118 Text en © 2018 Mermet et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Paper
Mermet, Jérôme
Yeung, Jake
Hurni, Clémence
Mauvoisin, Daniel
Gustafson, Kyle
Jouffe, Céline
Nicolas, Damien
Emmenegger, Yann
Gobet, Cédric
Franken, Paul
Gachon, Frédéric
Naef, Félix
Clock-dependent chromatin topology modulates circadian transcription and behavior
title Clock-dependent chromatin topology modulates circadian transcription and behavior
title_full Clock-dependent chromatin topology modulates circadian transcription and behavior
title_fullStr Clock-dependent chromatin topology modulates circadian transcription and behavior
title_full_unstemmed Clock-dependent chromatin topology modulates circadian transcription and behavior
title_short Clock-dependent chromatin topology modulates circadian transcription and behavior
title_sort clock-dependent chromatin topology modulates circadian transcription and behavior
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5900709/
https://www.ncbi.nlm.nih.gov/pubmed/29572261
http://dx.doi.org/10.1101/gad.312397.118
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