Skip to main content

Main menu

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
  • Submit
  • About
    • Editorial Board
    • PNAS Staff
    • FAQ
    • Accessibility Statement
    • Rights and Permissions
    • Site Map
  • Contact
  • Journal Club
  • Subscribe
    • Subscription Rates
    • Subscriptions FAQ
    • Open Access
    • Recommend PNAS to Your Librarian

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Home
Home
  • Log in
  • My Cart

Advanced Search

  • Home
  • Articles
    • Current
    • Special Feature Articles - Most Recent
    • Special Features
    • Colloquia
    • Collected Articles
    • PNAS Classics
    • List of Issues
  • Front Matter
    • Front Matter Portal
    • Journal Club
  • News
    • For the Press
    • This Week In PNAS
    • PNAS in the News
  • Podcasts
  • Authors
    • Information for Authors
    • Editorial and Journal Policies
    • Submission Procedures
    • Fees and Licenses
  • Submit
Research Article

Mistimed sleep disrupts circadian regulation of the human transcriptome

Simon N. Archer, Emma E. Laing, Carla S. Möller-Levet, Daan R. van der Veen, Giselda Bucca, Alpar S. Lazar, Nayantara Santhi, Ana Slak, Renata Kabiljo, Malcolm von Schantz, Colin P. Smith, and Derk-Jan Dijk
  1. Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom

See allHide authors and affiliations

PNAS first published January 21, 2014; https://doi.org/10.1073/pnas.1316335111
Simon N. Archer
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emma E. Laing
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carla S. Möller-Levet
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daan R. van der Veen
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Giselda Bucca
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alpar S. Lazar
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nayantara Santhi
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ana Slak
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Renata Kabiljo
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Malcolm von Schantz
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Colin P. Smith
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Derk-Jan Dijk
Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: d.j.dijk@surrey.ac.uk
  1. Edited by Joseph S. Takahashi, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX, and approved December 18, 2013 (received for review August 29, 2013)

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF
Loading

Significance

Disruption of the timing of the sleep–wake cycle and circadian rhythms, such as occurs during jet lag and shift work, leads to disordered physiological rhythms, but to what extent the molecular elements of circadian rhythm generation are affected is not known. Here, we show that delaying sleep by 4 h for 3 consecutive days leads to a sixfold reduction of circadian transcripts in the human blood transcriptome to just 1%, whereas, at the same time, the centrally driven circadian rhythm of melatonin is not affected. Genes and processes affected included those at the core of circadian rhythm generation and gene expression. The data have implications for understanding the negative health outcomes of disruption of the sleep–wake cycle.

Abstract

Circadian organization of the mammalian transcriptome is achieved by rhythmic recruitment of key modifiers of chromatin structure and transcriptional and translational processes. These rhythmic processes, together with posttranslational modification, constitute circadian oscillators in the brain and peripheral tissues, which drive rhythms in physiology and behavior, including the sleep–wake cycle. In humans, sleep is normally timed to occur during the biological night, when body temperature is low and melatonin is synthesized. Desynchrony of sleep–wake timing and other circadian rhythms, such as occurs in shift work and jet lag, is associated with disruption of rhythmicity in physiology and endocrinology. However, to what extent mistimed sleep affects the molecular regulators of circadian rhythmicity remains to be established. Here, we show that mistimed sleep leads to a reduction of rhythmic transcripts in the human blood transcriptome from 6.4% at baseline to 1.0% during forced desynchrony of sleep and centrally driven circadian rhythms. Transcripts affected are key regulators of gene expression, including those associated with chromatin modification (methylases and acetylases), transcription (RNA polymerase II), translation (ribosomal proteins, initiation, and elongation factors), temperature-regulated transcription (cold inducible RNA-binding proteins), and core clock genes including CLOCK and ARNTL (BMAL1). We also estimated the separate contribution of sleep and circadian rhythmicity and found that the sleep–wake cycle coordinates the timing of transcription and translation in particular. The data show that mistimed sleep affects molecular processes at the core of circadian rhythm generation and imply that appropriate timing of sleep contributes significantly to the overall temporal organization of the human transcriptome.

  • bloodomics
  • chronobiology
  • microarray
  • genomics
  • biological rhythms

Footnotes

  • ↵1S.N.A., E.E.L., and C.S.M.-L. contributed equally to this work.

  • ↵2To whom correspondence should be addressed. E-mail: d.j.dijk{at}surrey.ac.uk.
  • Author contributions: S.N.A., E.E.L., M.v.S., C.P.S., and D.-J.D. designed research; E.E.L., C.S.M.-L., D.R.v.d.V., G.B., A.S.L., N.S., A.S., and R.K. performed research; S.N.A., E.E.L., C.S.M.-L., G.B., and R.K. analyzed data; and S.N.A., E.E.L., C.S.M.-L., D.R.v.d.V., M.v.S., C.P.S., and D.-J.D. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE48113).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1316335111/-/DCSupplemental.

Freely available online through the PNAS open access option.

Next
Back to top
Article Alerts
Email Article

Thank you for your interest in spreading the word on PNAS.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Mistimed sleep disrupts circadian regulation of the human transcriptome
(Your Name) has sent you a message from PNAS
(Your Name) thought you would like to see the PNAS web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Circadian desynchrony and the human transcriptome
Simon N. Archer, Emma E. Laing, Carla S. Möller-Levet, Daan R. van der Veen, Giselda Bucca, Alpar S. Lazar, Nayantara Santhi, Ana Slak, Renata Kabiljo, Malcolm von Schantz, Colin P. Smith, Derk-Jan Dijk
Proceedings of the National Academy of Sciences Jan 2014, 201316335; DOI: 10.1073/pnas.1316335111

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Circadian desynchrony and the human transcriptome
Simon N. Archer, Emma E. Laing, Carla S. Möller-Levet, Daan R. van der Veen, Giselda Bucca, Alpar S. Lazar, Nayantara Santhi, Ana Slak, Renata Kabiljo, Malcolm von Schantz, Colin P. Smith, Derk-Jan Dijk
Proceedings of the National Academy of Sciences Jan 2014, 201316335; DOI: 10.1073/pnas.1316335111
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Mendeley logo Mendeley
Proceedings of the National Academy of Sciences: 118 (14)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

  • Article
  • Figures & SI
  • Info & Metrics
  • PDF

You May Also be Interested in

Smoke emanates from Japan’s Fukushima nuclear power plant a few days after tsunami damage
Core Concept: Muography offers a new way to see inside a multitude of objects
Muons penetrate much further than X-rays, they do essentially zero damage, and they are provided for free by the cosmos.
Image credit: Science Source/Digital Globe.
Water from a faucet fills a glass.
News Feature: How “forever chemicals” might impair the immune system
Researchers are exploring whether these ubiquitous fluorinated molecules might worsen infections or hamper vaccine effectiveness.
Image credit: Shutterstock/Dmitry Naumov.
Venus flytrap captures a fly.
Journal Club: Venus flytrap mechanism could shed light on how plants sense touch
One protein seems to play a key role in touch sensitivity for flytraps and other meat-eating plants.
Image credit: Shutterstock/Kuttelvaserova Stuchelova.
Illustration of groups of people chatting
Exploring the length of human conversations
Adam Mastroianni and Daniel Gilbert explore why conversations almost never end when people want them to.
Listen
Past PodcastsSubscribe
Horse fossil
Mounted horseback riding in ancient China
A study uncovers early evidence of equestrianism in ancient China.
Image credit: Jian Ma.

Similar Articles

Site Logo
Powered by HighWire
  • Submit Manuscript
  • Twitter
  • Facebook
  • RSS Feeds
  • Email Alerts

Articles

  • Current Issue
  • Special Feature Articles – Most Recent
  • List of Issues

PNAS Portals

  • Anthropology
  • Chemistry
  • Classics
  • Front Matter
  • Physics
  • Sustainability Science
  • Teaching Resources

Information

  • Authors
  • Editorial Board
  • Reviewers
  • Subscribers
  • Librarians
  • Press
  • Cozzarelli Prize
  • Site Map
  • PNAS Updates
  • FAQs
  • Accessibility Statement
  • Rights & Permissions
  • About
  • Contact

Feedback    Privacy/Legal

Copyright © 2021 National Academy of Sciences. Online ISSN 1091-6490