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The global and promoter-centric 3D genome organization temporally resolved during a circadian cycle

Published version
Peer-reviewed

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Authors

Furlan-Magaril, Mayra  ORCID logo  https://orcid.org/0000-0002-6771-6631
Ando-Kuri, Masami 
Arzate-Mejía, Rodrigo G. 
Morf, Jörg 
Cairns, Jonathan 

Abstract

Abstract: Background: Circadian gene expression is essential for organisms to adjust their physiology and anticipate daily changes in the environment. The molecular mechanisms controlling circadian gene transcription are still under investigation. In particular, how chromatin conformation at different genomic scales and regulatory elements impact rhythmic gene expression has been poorly characterized. Results: Here we measure changes in the spatial chromatin conformation in mouse liver using genome-wide and promoter-capture Hi-C alongside daily oscillations in gene transcription. We find topologically associating domains harboring circadian genes that switch assignments between the transcriptionally active and inactive compartment at different hours of the day, while their boundaries stably maintain their structure over time. To study chromatin contacts of promoters at high resolution over time, we apply promoter capture Hi-C. We find circadian gene promoters displayed a maximal number of chromatin contacts at the time of their peak transcriptional output. Furthermore, circadian genes, as well as contacted and transcribed regulatory elements, reach maximal expression at the same timepoints. Anchor sites of circadian gene promoter loops are enriched in DNA binding sites for liver nuclear receptors and other transcription factors, some exclusively present in either rhythmic or stable contacts. Finally, by comparing the interaction profiles between core clock and output circadian genes, we show that core clock interactomes are more dynamic compared to output circadian genes. Conclusion: Our results identify chromatin conformation dynamics at different scales that parallel oscillatory gene expression and characterize the repertoire of regulatory elements that control circadian gene transcription through rhythmic or stable chromatin configurations.

Description

Funder: FP7 Ideas: European Research Council; doi: http://dx.doi.org/10.13039/100011199; Grant(s): 259743

Keywords

Research, Regulatory elements, Genome 3D organization, Promoter interactions, Circadian gene expression, Transcription regulation, TADs, Chromatin compartments, Enhancers, Circadian rhythms

Journal Title

Genome Biology

Conference Name

Journal ISSN

1474-760X

Volume Title

22

Publisher

BioMed Central
Sponsorship
UNAM Technology Innovation and Research Support Program PAPIIT (IN207319)
Consejo Nacional de Ciencia y Tecnología (15758)
Biotechnology and Biological Sciences Research Council (BB/J004480/1)
European Research Council (340152)