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

Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis

Mikhail Geyfman, Vivek Kumar, Qiang Liu, Rolando Ruiz, William Gordon, Francisco Espitia, Eric Cam, Sarah E. Millar, Padhraic Smyth, Alexander Ihler, Joseph S. Takahashi, and Bogi Andersen
  1. Departments of aBiological Chemistry,
  2. dComputer Science, and
  3. gMedicine,
  4. eCenter for Complex Biological Systems, and
  5. hInstitute for Genomics and Bioinformatics, University of California, Irvine, CA 92697;
  6. bDepartment of Neuroscience and
  7. cHoward Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390; and
  8. fDepartment of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

See allHide authors and affiliations

PNAS first published July 2, 2012; https://doi.org/10.1073/pnas.1209592109
Mikhail Geyfman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vivek Kumar
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Qiang Liu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rolando Ruiz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
William Gordon
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Francisco Espitia
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eric Cam
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sarah E. Millar
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Padhraic Smyth
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander Ihler
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joseph S. Takahashi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Joseph.Takahashi@UTSouthwestern.edu bogi@uci.edu
Bogi Andersen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: Joseph.Takahashi@UTSouthwestern.edu bogi@uci.edu
  1. Contributed by Joseph S. Takahashi, June 6, 2012 (sent for review March 24, 2012)

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

Abstract

The role of the circadian clock in skin and the identity of genes participating in its chronobiology remain largely unknown, leading us to define the circadian transcriptome of mouse skin at two different stages of the hair cycle, telogen and anagen. The circadian transcriptomes of telogen and anagen skin are largely distinct, with the former dominated by genes involved in cell proliferation and metabolism. The expression of many metabolic genes is antiphasic to cell cycle-related genes, the former peaking during the day and the latter at night. Consistently, accumulation of reactive oxygen species, a byproduct of oxidative phosphorylation, and S-phase are antiphasic to each other in telogen skin. Furthermore, the circadian variation in S-phase is controlled by BMAL1 intrinsic to keratinocytes, because keratinocyte-specific deletion of Bmal1 obliterates time-of-day–dependent synchronicity of cell division in the epidermis leading to a constitutively elevated cell proliferation. In agreement with higher cellular susceptibility to UV-induced DNA damage during S-phase, we found that mice are most sensitive to UVB-induced DNA damage in the epidermis at night. Because in the human epidermis maximum numbers of keratinocytes go through S-phase in the late afternoon, we speculate that in humans the circadian clock imposes regulation of epidermal cell proliferation so that skin is at a particularly vulnerable stage during times of maximum UV exposure, thus contributing to the high incidence of human skin cancers.

  • Arntl gene
  • circadian rhythm
  • UVB damage
  • cell cycle

Footnotes

  • ↵1To whom correspondence may be addressed. E-mail: Joseph.Takahashi{at}UTSouthwestern.edu or bogi{at}uci.edu.
  • Author contributions: M.G., V.K., S.E.M., J.S.T., and B.A. designed research; M.G., R.R., W.G., F.E., and E.C. performed research; M.G., V.K., Q.L., W.G., P.S., A.I., J.S.T., and B.A. analyzed data; and M.G., V.K., J.S.T., and B.A. wrote the paper.

  • The authors declare no conflict of interest.

  • 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. GSE38625).

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1209592109/-/DCSupplemental.

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.
Brain and muscle Arnt-like protein-1 (BMAL1) controls circadian cell proliferation and susceptibility to UVB-induced DNA damage in the epidermis
(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 cell proliferation in epidermis
Mikhail Geyfman, Vivek Kumar, Qiang Liu, Rolando Ruiz, William Gordon, Francisco Espitia, Eric Cam, Sarah E. Millar, Padhraic Smyth, Alexander Ihler, Joseph S. Takahashi, Bogi Andersen
Proceedings of the National Academy of Sciences Jul 2012, 201209592; DOI: 10.1073/pnas.1209592109

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Circadian cell proliferation in epidermis
Mikhail Geyfman, Vivek Kumar, Qiang Liu, Rolando Ruiz, William Gordon, Francisco Espitia, Eric Cam, Sarah E. Millar, Padhraic Smyth, Alexander Ihler, Joseph S. Takahashi, Bogi Andersen
Proceedings of the National Academy of Sciences Jul 2012, 201209592; DOI: 10.1073/pnas.1209592109
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 (15)
Current Issue

Submit

Sign up for Article Alerts

Jump to section

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

You May Also be Interested in

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.
Reflection of clouds in the still waters of Mono Lake in California.
Inner Workings: Making headway with the mysteries of life’s origins
Recent experiments and simulations are starting to answer some fundamental questions about how life came to be.
Image credit: Shutterstock/Radoslaw Lecyk.
Cave in coastal Kenya with tree growing in the middle.
Journal Club: Small, sharp blades mark shift from Middle to Later Stone Age in coastal Kenya
Archaeologists have long tried to define the transition between the two time periods.
Image credit: Ceri Shipton.
Mouse fibroblast cells. Electron bifurcation reactions keep mammalian cells alive.
Exploring electron bifurcation
Jonathon Yuly, David Beratan, and Peng Zhang investigate how electron bifurcation reactions work.
Listen
Past PodcastsSubscribe
Panda bear hanging in a tree
How horse manure helps giant pandas tolerate cold
A study finds that giant pandas roll in horse manure to increase their cold tolerance.
Image credit: Fuwen Wei.

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