Home LiteratureArticle Details
PMID: 19078963 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Circadian gene expression is resilient to large fluctuations in overall transcription rates.

The EMBO journal ·Vol. 28 ·No. 2 ·2009-01-21 ·Pages 123-34

Dibner C, Sage D, Unser M, Bauer C, d'Eysmond T, Naef F, Schibler U

Abstract

Mammalian circadian oscillators are considered to rely on transcription/translation feedback loops in clock gene expression. The major and essential loop involves the autorepression of cryptochrome (Cry1, Cry2) and period (Per1, Per2) genes. The rhythm-generating circuitry is functional in most cell types, including cultured fibroblasts. Using this system, we show that significant reduction in RNA polymerase II-dependent transcription did not abolish circadian oscillations, but surprisingly accelerated them. A similar period shortening was observed at reduced incubation temperatures in wild-type mouse fibroblasts, but not in cells lacking Per1. Our data suggest that mammalian circadian oscillators are resilient to large fluctuations in general transcription rates and temperature, and that PER1 has an important function in transcription and temperature compensation.

MeSH Terms
Animals Cell Cycle Proteins/genetics,metabolism Circadian Rhythm/physiology Cryptochromes Feedback, Physiological Flavoproteins/metabolism Mice NIH 3T3 Cells Nuclear Proteins/genetics,metabolism Period Circadian Proteins RNA Polymerase II/metabolism Temperature Transcription Factors/genetics,metabolism Transcription, Genetic
Chemicals
Cell Cycle Proteins Cry1 protein, mouse Cry2 protein, mouse Cryptochromes Flavoproteins Nuclear Proteins Per1 protein, mouse Per2 protein, mouse Period Circadian Proteins Transcription Factors RNA Polymerase II
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Dibner Charna
Department of Molecular Biology & NCCR Frontiers in Genetics, University of Geneva, Geneva, Switzerland.
Sage Daniel
Unser Michael
Bauer Christoph
d'Eysmond Thomas
Naef Felix
Schibler Ueli
References (66)
66 references, click to expand
  1. Inhibitors of transcription such as 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole and isoquinoline sulfonamide derivatives (H-8 and H-7) promote dephosphorylation of the carboxyl-terminal domain of RNA polymerase II largest subunit.
    J Biol Chem. 1994 May 6;269(18):13331-6 PMID: 7513701
  2. Temperature compensation in circadian clock models.
    J Theor Biol. 2005 Apr 21;233(4):453-68 PMID: 15748908
  3. Toward a detailed computational model for the mammalian circadian clock.
    Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):7051-6 PMID: 12775757
  4. Regulation of telomeric repeat binding factor 1 binding to telomeres by casein kinase 2-mediated phosphorylation.
    J Biol Chem. 2008 May 16;283(20):14144-52 PMID: 18347021
  5. Control of mammalian circadian rhythm by CKIepsilon-regulated proteasome-mediated PER2 degradation.
    Mol Cell Biol. 2005 Apr;25(7):2795-807 PMID: 15767683
  6. Circadian transcription contributes to core period determination in Drosophila.
    PLoS Biol. 2008 May 20;6(5):e119 PMID: 18494558
  7. Disruption of mCry2 restores circadian rhythmicity in mPer2 mutant mice.
    Genes Dev. 2002 Oct 15;16(20):2633-8 PMID: 12381662
  8. Cell size regulation, a mechanism that controls cellular RNA accumulation: consequences on regulation of the ubiquitous transcription factors Oct1 and NF-Y and the liver-enriched transcription factor DBP.
    J Cell Biol. 1995 Feb;128(4):467-83 PMID: 7532171
  9. Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drives circadian Dbp transcription and chromatin transitions.
    Nat Genet. 2006 Mar;38(3):369-74 PMID: 16474407
  10. SIRT1 regulates circadian clock gene expression through PER2 deacetylation.
    Cell. 2008 Jul 25;134(2):317-28 PMID: 18662546
  11. A serum shock induces circadian gene expression in mammalian tissue culture cells.
    Cell. 1998 Jun 12;93(6):929-37 PMID: 9635423
  12. Transcriptional blockade induces p53-dependent apoptosis associated with translocation of p53 to mitochondria.
    J Biol Chem. 2005 May 13;280(19):19166-76 PMID: 15753095
  13. Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS).
    Genes Dev. 2006 Oct 1;20(19):2660-72 PMID: 16983144
  14. A role for casein kinase 2alpha in the Drosophila circadian clock.
    Nature. 2002 Dec 19-26;420(6917):816-20 PMID: 12447397
  15. Molecular insights into human daily behavior.
    Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1602-7 PMID: 18227513
  16. Clock genes, oscillators, and cellular networks in the suprachiasmatic nuclei.
    J Biol Rhythms. 2004 Oct;19(5):400-13 PMID: 15534320
  17. TFIIH plays an essential role in RNA polymerase I transcription.
    Cell. 2002 May 3;109(3):297-306 PMID: 12015980
  18. PER-TIM interactions with the photoreceptor cryptochrome mediate circadian temperature responses in Drosophila.
    PLoS Biol. 2007 Jun;5(6):e146 PMID: 17535111
  19. Temperature compensation of circadian rhythms: control of the period in a model for circadian oscillations of the per protein in Drosophila.
    Chronobiol Int. 1997 Sep;14(5):511-20 PMID: 9298286
  20. Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome.
    Nature. 2005 Mar 31;434(7033):640-4 PMID: 15800623
  21. Cycling of CRYPTOCHROME proteins is not necessary for circadian-clock function in mammalian fibroblasts.
    Curr Biol. 2007 Jul 3;17(13):1091-100 PMID: 17583506
  22. Glucose down-regulates Per1 and Per2 mRNA levels and induces circadian gene expression in cultured Rat-1 fibroblasts.
    J Biol Chem. 2002 Nov 15;277(46):44244-51 PMID: 12213820
  23. Intercellular coupling confers robustness against mutations in the SCN circadian clock network.
    Cell. 2007 May 4;129(3):605-16 PMID: 17482552
  24. A colorful model of the circadian clock.
    Cell. 2006 Jan 27;124(2):233-6 PMID: 16439193
  25. The period length of fibroblast circadian gene expression varies widely among human individuals.
    PLoS Biol. 2005 Oct;3(10):e338 PMID: 16167846
  26. Transcriptional feedback oscillators: maybe, maybe not...
    J Biol Rhythms. 2006 Apr;21(2):83-92 PMID: 16603673
  27. ON TEMPERATURE INDEPENDENCE IN THE CLOCK SYSTEM CONTROLLING EMERGENCE TIME IN DROSOPHILA.
    Proc Natl Acad Sci U S A. 1954 Oct;40(10):1018-29 PMID: 16589583
  28. Dynamical signatures of cellular fluctuations and oscillator stability in peripheral circadian clocks.
    Mol Syst Biol. 2007;3:93 PMID: 17353935
  29. Interlocked feedback loops of the circadian clock of Neurospora crassa.
    Mol Microbiol. 2008 Apr;68(2):255-62 PMID: 18312266
  30. Post-transcriptional regulation contributes to Drosophila clock gene mRNA cycling.
    EMBO J. 1997 Dec 1;16(23):7146-55 PMID: 9384591
  31. Clustering of RNA polymerase B molecules in the 5' moiety of the adult beta-globin gene of hen erythrocytes.
    Nucleic Acids Res. 1981 Jun 11;9(11):2589-98 PMID: 6269056
  32. Reciprocal behaviour associated with altered homeostasis and photosensitivity of Drosophila clock mutants.
    J Neurogenet. 1989 Sep;6(1):1-10 PMID: 2506319
  33. An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome.
    Science. 2001 Feb 9;291(5506):1040-3 PMID: 11232563
  34. A proposal for temperature compensation of the circadian rhythm in Drosophila based on dimerization of the per protein.
    Chronobiol Int. 1997 Sep;14(5):521-9 PMID: 9298287
  35. In vivo degradation of RNA polymerase II largest subunit triggered by alpha-amanitin.
    Nucleic Acids Res. 1996 Aug 1;24(15):2924-9 PMID: 8760875
  36. Circadian gene expression in mammalian fibroblasts revealed by real-time luminescence reporting: temperature compensation and damping.
    Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):16089-94 PMID: 14657355
  37. Phenotypic rescue of a peripheral clock genetic defect via SCN hierarchical dominance.
    Cell. 2002 Jul 12;110(1):107-17 PMID: 12151001
  38. Reduced RNA polymerase II transcription in intact and permeabilized Cockayne syndrome group B cells.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4306-11 PMID: 9113985
  39. Posttranslational mechanisms regulate the mammalian circadian clock.
    Cell. 2001 Dec 28;107(7):855-67 PMID: 11779462
  40. Ubiquitination of RNA polymerase II large subunit signaled by phosphorylation of carboxyl-terminal domain.
    Proc Natl Acad Sci U S A. 1999 May 25;96(11):6054-9 PMID: 10339540
  41. Dual KaiC-based oscillations constitute the circadian system of cyanobacteria.
    Genes Dev. 2008 Jun 1;22(11):1513-21 PMID: 18477603
  42. Differential display of DNA-binding proteins reveals heat-shock factor 1 as a circadian transcription factor.
    Genes Dev. 2008 Feb 1;22(3):331-45 PMID: 18245447
  43. Circadian gene expression in individual fibroblasts: cell-autonomous and self-sustained oscillators pass time to daughter cells.
    Cell. 2004 Nov 24;119(5):693-705 PMID: 15550250
  44. Drosophila DBT lacking protein kinase activity produces long-period and arrhythmic circadian behavioral and molecular rhythms.
    Mol Cell Biol. 2007 Dec;27(23):8049-64 PMID: 17893330
  45. A TBP-containing multiprotein complex (TIF-IB) mediates transcription specificity of murine RNA polymerase I.
    Nucleic Acids Res. 1993 Sep 11;21(18):4180-6 PMID: 8414971
  46. Circadian rhythms and molecular noise.
    Chaos. 2006 Jun;16(2):026110 PMID: 16822042
  47. Post-translational modifications regulate the ticking of the circadian clock.
    Nat Rev Mol Cell Biol. 2007 Feb;8(2):139-48 PMID: 17245414
  48. Regulation of flagellar dynein by the axonemal central apparatus.
    Cell Motil Cytoskeleton. 2002 May;52(1):33-42 PMID: 11977081
  49. Real time quantitative PCR.
    Genome Res. 1996 Oct;6(10):986-94 PMID: 8908518
  50. A detailed predictive model of the mammalian circadian clock.
    Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14806-11 PMID: 14657377
  51. PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues.
    Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5339-46 PMID: 14963227
  52. Nonredundant roles of the mPer1 and mPer2 genes in the mammalian circadian clock.
    Cell. 2001 Jun 1;105(5):683-94 PMID: 11389837
  53. Temperature compensation and temperature resetting of circadian rhythms in mammalian cultured fibroblasts.
    Genes Cells. 2003 Aug;8(8):713-20 PMID: 12875656
  54. Circadian clocks limited by noise.
    Nature. 2000 Jan 20;403(6767):267-8 PMID: 10659837
  55. Finding new clock components: past and future.
    J Biol Rhythms. 2004 Oct;19(5):339-47 PMID: 15536063
  56. Structural basis of transcription: alpha-amanitin-RNA polymerase II cocrystal at 2.8 A resolution.
    Proc Natl Acad Sci U S A. 2002 Feb 5;99(3):1218-22 PMID: 11805306
  57. Inhibition of transcription blocks cell cycle progression of NIH3T3 fibroblasts specifically in G1.
    J Cell Sci. 1993 May;105 ( Pt 1):113-22 PMID: 8360267
  58. Circadian clock control by SUMOylation of BMAL1.
    Science. 2005 Aug 26;309(5739):1390-4 PMID: 16109848
  59. No transcription-translation feedback in circadian rhythm of KaiC phosphorylation.
    Science. 2005 Jan 14;307(5707):251-4 PMID: 15550625
  60. Reconstitution of circadian oscillation of cyanobacterial KaiC phosphorylation in vitro.
    Science. 2005 Apr 15;308(5720):414-5 PMID: 15831759
  61. Rhythmic E-box binding by CLK-CYC controls daily cycles in per and tim transcription and chromatin modifications.
    Mol Cell Biol. 2008 Jul;28(14):4642-52 PMID: 18474612
  62. A temperature-compensated model for circadian rhythms that can be entrained by temperature cycles.
    J Theor Biol. 2007 May 7;246(1):195-204 PMID: 17275853
  63. Casein kinase I: another cog in the circadian clockworks.
    Chronobiol Int. 2001 May;18(3):389-98 PMID: 11475410
  64. Resetting of circadian time in peripheral tissues by glucocorticoid signaling.
    Science. 2000 Sep 29;289(5488):2344-7 PMID: 11009419
  65. Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau.
    Science. 2000 Apr 21;288(5465):483-92 PMID: 10775102
  66. Feedback of the Drosophila period gene product on circadian cycling of its messenger RNA levels.
    Nature. 1990 Feb 8;343(6258):536-40 PMID: 2105471
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/emboj.2008.262
Published
2009-01-21
Epub
2008-00-11
Pages
123-34
Language
English
Region
England
NLM ID
8208664
PMCID
PMC2634731
Subset
IM
Corrections
CommentIn
PMID: 19158661
External Links
PubMed source DOI: 10.1038/emboj.2008.262 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2