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Roles of RORα on Transcriptional Expressions in the Mammalian Circadian Regulatory System

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Advances in Bioinformatics and Computational Biology (BSB 2013)

Part of the book series: Lecture Notes in Computer Science ((LNBI,volume 8213))

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Abstract

REV-ERBα and RORα are involved in the molecular regulatory system of mammalian circadian cycles, expressing opposite interactions on Bmal1 expression, inhibition and activation, respectively. REV-ERBα has been thought to be the major regulator of gene expressions in phases, which is more than the role of RORα. This paper gives a contrary result to this, showing a prominent role of RORα in determining phase relations of the gene expression cycles. Computer simulations are conducted for the predictions of this RORα role, in addition, one of these predictions is supported by a biological experiment that shows combinatory effect of RORα and CRY on Bmal1 transcription.

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References

  1. Dunlap, J.C.: Molecular bases for circadian clocks. Cell 96, 271–290 (1999)

    Article  Google Scholar 

  2. Shearman, L.P., Sriam, S., Weaver, D.R., Maywood, E.S., Chaves, I., Zheng, B., Kume, K., Lee, C.C., van der Horst, G.T., Hastings, M.H., Reppert, S.M.: Interacting molecular loops in the mammalian circadian clock. Science 288, 1013–1019 (2000)

    Article  Google Scholar 

  3. Preitner, N., Damiola, F., Lopez-Molina, L., Zakany, J., Duboule, D., Albrecht, U., Schibler, U.: The orphan nuclear receptor REV-ERBα controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110, 251–260 (2002)

    Article  Google Scholar 

  4. Goldbeter, A.: Computational approaches to cellular rhythms. Nature 420, 238–245 (2002)

    Article  Google Scholar 

  5. Leloup, J., Goldbeter, A.: Toward a detailed computational model of the mammalian circadian clock. Proc. Natl. Acad. Sci. USA 100, 7051–7056 (2003)

    Article  Google Scholar 

  6. Forger, D.B., Peskin, C.S.: A detailed predictive model of the mammalian circadian clock. Proc. Natl. Acad. Sci. USA 100, 14806–14811 (2003)

    Article  Google Scholar 

  7. Becker-Weimann, S., Wolf, J., Kramer, A., Herzel, H.: A model of the mammalian circadian oscillator including the REV-ERBα module. Genome Inform. 15, 3–12 (2004)

    Google Scholar 

  8. Leloup, J., Goldbeter, A.: Modeling the circadian clock: from molecular mechanism to physiological disorders. BioEssays 30, 590–600 (2008)

    Article  Google Scholar 

  9. Becker-Weimann, S., Wolf, J., Herzel, H., Kramer, A.: Modeling feedback loops of the mammalian circadian oscillator. Biophysical J. 87, 3023–3034 (2004)

    Article  Google Scholar 

  10. Sato, T.K., Panda, S., Miraglia, L.J., Reyes, T.M., Rudic, R.D., McNamara, P., Naik, K.A., FitzGerald, G.A., Kay, S.A., Hogenesch, J.B.: A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron 43, 527–537 (2004)

    Article  Google Scholar 

  11. Akashi, M., Takumi, T.: The orphan nuclear receptor RORα regulates circadian transcription of the mammalian core-clock Bmal1. Nat. Struc. Mol. Biol. 12, 441–448 (2005)

    Article  Google Scholar 

  12. Guillaumond, F., Dardente, H., Giguere, V., Germakian, N.: Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors. J. Biol. Rhythms 20, 391–403 (2005)

    Article  Google Scholar 

  13. Liu, A.C., Tran, H.G., Zhang, E.E., Priest, A.A., Welsh, D.K., Kay, S.A.: Redundant function of REV-ERVα and β non-essential role of Bmal1 cycling in transcriptional regulation of intracelluar circadian rhythms. PLoS Genetics 4(2), e10000023 (2008)

    Google Scholar 

  14. Mirsky, H.P., Liu, A.C., Welsh, D.K., Kay, S.A., Doyle, F.J.: A model of the cell-autonomous mammalian circadian clock. Proc. Natl. Acad. Sci. USA 106, 11107–11112 (2009)

    Article  Google Scholar 

  15. Korenčič, A., Bordyugov, G., Košir, R., Rozman, D., Goličnik, M.: The interplay of cis-regulatory elements rules circadian rhythms in mouse liver. PLOS ONE 7(11), e46835 (2012)

    Google Scholar 

  16. Relógio, A., Westermark, P.O., Wallach, T., Schellenberg, K., Kramer, A.: Tuning the mammalian circadian clock: Robust synergy of two loops. PLoS Comput. Biol. 7(12), e1002309 (2011)

    Google Scholar 

  17. Takeda, Y., Jothi, R., Birault, V., Jetten, A.M.: RORγ directly regulates the circadian expression of clock genes and downstream targets in vivo. Nucleic Acid Research 40, 8519–8535 (2012)

    Article  Google Scholar 

  18. Solt, L.A., Burris, T.P.: Action of RORs and their ligands in (patho)physiology. Trends in Endocrinology and Metabolism 23, 619–627 (2012)

    Article  Google Scholar 

  19. Du, J., Xu, R.: RORα, a potental tumor supressor and therapeutic target of breast cancer. Int. J. Mol. Sci. 26, 15755–15766 (2012)

    Article  Google Scholar 

  20. Matsuno, H., Tanaka, Y., Aoshima, H., Doi, A., Matsui, M., Miyano, S.: Biopathways representation and simulation on hybrid functional Petri net. In Silico Biol. 3, 389–404 (2003)

    Google Scholar 

  21. Matsuno, H., Inouye, S.T., Okitsu, Y., Fujii, Y., Miyano, S.: A new regulatory interaction suggested by simulations for circadian genetic control mechanism in mammals. J. Bioinform. Comput. Biol. 4, 139–153 (2006)

    Article  Google Scholar 

  22. Cell Illustrator, http://www.cellillustrator.com

  23. Reppert, S.M., Weaver, D.R.: Coordination of circadian timing in mammals. Nature 418, 935–941 (2002)

    Article  Google Scholar 

  24. Oishi, K., Fukui, H., Ishida, N.: Rhythmic expression of BMAL1 mRNA is altered in Clock mutant mice: differential regulation in the suprachiasmatic nucleus and peripheral tissues. Biochem. Biophys. Res. Commun. 268, 164–171 (2000)

    Article  Google Scholar 

  25. Onishi, H., Yamaguchi, S., Yagita, K., Ishida, Y., Dong, X., Kimura, H., Jing, Z., Ohara, H., Okamura, H.: Rev-erbalpha gene expression in the mouse brain with special emphasis on its circadian profiles in the suprachiasmatic nucleus. J. Neurosci. Res. 68, 551–557 (2002)

    Article  Google Scholar 

  26. Lee, H., Chen, R., Kin, H., Etchegaray, J., Weaver, D.R., Lee, C.: The period of the circadian oscillator is primarily determined by the balance between casein kinase 1 an protein phosphatase 1. Proc. Natl. Acad. Sci. USA 108, 16451–16456 (2011)

    Article  Google Scholar 

  27. Hirano, A., Yumimoto, K., Tsunematsu, R., Matsumoto, M., Oyama, M., Kozuka-Hata, H., Nagasawa, T., Lanjakornsiripan, D., Nakayama, K.I., Fukada, Y.: FBXL21 regulates oscillation of the circadian clock through ubiquitination and stabilization of Cryptochromes. Cell 152, 1106–1118 (2013)

    Article  Google Scholar 

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Authors and Affiliations

  1. Graduate School of Science and Engineering, Yamaguchi University, Japan

    Hiroshi Matsuno

  2. The Research Institute for Time Studies, Yamaguchi University, japan

    Makoto Akashi

Authors
  1. Hiroshi Matsuno
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  2. Makoto Akashi
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Editor information

Editors and Affiliations

  1. Institute of Chemistry, University of São Paulo, Avenida Prof. Lineu Prestes, 748 sala 911, 05508-000, São Paulo, SP, Brazil

    João C. Setubal

  2. School of Computing, Facom-UFMS, Federal University of Mato Grosso do Sul, CP 549, Mato Grosso do Sul, 79070-900, MS, Brazil

    Nalvo F. Almeida

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Matsuno, H., Akashi, M. (2013). Roles of RORα on Transcriptional Expressions in the Mammalian Circadian Regulatory System. In: Setubal, J.C., Almeida, N.F. (eds) Advances in Bioinformatics and Computational Biology. BSB 2013. Lecture Notes in Computer Science(), vol 8213. Springer, Cham. https://doi.org/10.1007/978-3-319-02624-4_2

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  • DOI: https://doi.org/10.1007/978-3-319-02624-4_2

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-02623-7

  • Online ISBN: 978-3-319-02624-4

  • eBook Packages: Computer ScienceComputer Science (R0)

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