Hepatic Clocks

  • Ueli SchiblerEmail author
  • Gad Asher
  • Camille Saini
  • Jörg Morf
  • Hans Reinke


Most physiological processes are subject to daily ­oscillations that are driven by an endogenous circadian clock. These include rest–activity cycles, cardiovascular functions such as heart rate and blood pressure, the production and secretion of hormones, renal plasma flow and urine production, in addition to metabolic functions of organs associated with the gastrointestinal tract (for review and references, see [1–4]). Since most metabolic functions oscillate in a daily manner, the liver is an organ for which circadian timing is particularly obvious. Thus, genome-wide transcriptome profiling studies have revealed that depending on the stringency of algorithms used for the extraction of oscillating transcripts between 2 and 10% of all liver mRNAs accumulate in a rhythmic fashion [5–10]. The majority of these transcripts encode enzymes and regulators involved in the metabolism of fatty acids, cholesterol, bile acids, carbohydrates, and xenobiotics. Several signaling pathways relevant for hepatic clock outputs (e.g., signaling through PPARs, CAR, LXR, and FXR) are elaborated in previous chapters of this issue. In this chapter, we shall thus focus on putative signaling pathways related to input pathways into the liver clock. Specifically, we will discuss current views and hypothesis on how the master pacemaker in the brain’s suprachiasmatic nucleus (SCN) synchronizes peripheral clocks, in particular those operative in liver. We will also present some findings made with cultured fibroblasts, since these cells have served as a model system in most in vitro studies. Some of the signaling routes outlined below remain speculative, and their detailed analysis requires additional investigations.


Bile Acid Circadian Clock Serum Response Factor Circadian Oscillator Peripheral Clock 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Gachon F, Nagoshi E, Brown SA, Ripperger J, Schibler U (2004) The mammalian circadian timing system: from gene expression to physiology. Chromosoma 113(3):103–12CrossRefPubMedGoogle Scholar
  2. 2.
    Liu AC, Lewis WG, Kay SA (2007) Mammalian circadian signaling networks and therapeutic targets. Nat Chem Biol 3(10):630–9CrossRefPubMedGoogle Scholar
  3. 3.
    Lowrey PL, Takahashi JS (2004) Mammalian circadian biology: elucidating genome-wide levels of temporal organization. Annu Rev Genomics Hum Genet 5:407–41CrossRefPubMedGoogle Scholar
  4. 4.
    Takahashi JS, Hong HK, Ko CH, McDearmon EL (2008) The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev 9(10): 764–75CrossRefGoogle Scholar
  5. 5.
    Akhtar RA, Reddy AB, Maywood ES et al (2002) Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus. Curr Biol 12(7):540–50CrossRefPubMedGoogle Scholar
  6. 6.
    Duffield GE, Best JD, Meurers BH, Bittner A, Loros JJ, Dunlap JC (2002) Circadian programs of transcriptional activation, signaling, and protein turnover revealed by microarray analysis of Mammalian cells. Curr Biol 12(7):551–7CrossRefPubMedGoogle Scholar
  7. 7.
    Kornmann B, Schaad O, Bujard H, Takahashi JS, Schibler U (2007) System-driven and oscillator-dependent circadian transcription in mice with a conditionally active liver clock. PLoS Biol 5(2):e34CrossRefGoogle Scholar
  8. 8.
    Panda S (2007) Multiple photopigments entrain the Mammalian circadian oscillator. Neuron 53(5):619–21CrossRefPubMedGoogle Scholar
  9. 9.
    Storch KF, Lipan O, Leykin I et al (2002) Extensive and divergent circadian gene expression in liver and heart. Nature 417(6884):78–83CrossRefPubMedGoogle Scholar
  10. 10.
    Walker JR, Hogenesch JB (2005) RNA profiling in circadian biology. Methods Enzymol 393:366–76CrossRefPubMedGoogle Scholar
  11. 11.
    Kornmann B, Schaad O, Reinke H, Saini C, Schibler U (2007) Regulation of circadian gene expression in liver by systemic signals and hepatocyte oscillators. Cold Spring Harb Symp Quant Biol 72:319–30CrossRefPubMedGoogle Scholar
  12. 12.
    Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418(6901):935–41CrossRefPubMedGoogle Scholar
  13. 13.
    Okamura H (2007) Suprachiasmatic nucleus clock time in the mammalian circadian system. Cold Spring Harb Symp Quant Biol 72:551–6CrossRefPubMedGoogle Scholar
  14. 14.
    Yan L, Karatsoreos I, Lesauter J et al (2007) Exploring spatiotemporal organization of SCN circuits. Cold Spring Harbor Symp Quant Biol 72:527–41CrossRefPubMedGoogle Scholar
  15. 15.
    Kennaway DJ (2004) Resetting the suprachiasmatic nucleus clock. Front Biosci 9:56–62CrossRefPubMedGoogle Scholar
  16. 16.
    Meijer JH, Schwartz WJ (2003) In search of the pathways for light-induced pacemaker resetting in the suprachiasmatic nucleus. J Biol Rhythms 18(3):235–49CrossRefPubMedGoogle Scholar
  17. 17.
    Sack RL, Auckley D, Auger RR et al (2007) Circadian rhythm sleep disorders: part I, basic principles, shift work and jet lag disorders. An American Academy of Sleep Medicine review. Sleep 1;30(11):1460–83Google Scholar
  18. 18.
    Waterhouse J, Nevill A, Finnegan J et al (2005) Further assessments of the relationship between jet lag and some of its symptoms. Chronobiol Int 22(1):121–36CrossRefPubMedGoogle Scholar
  19. 19.
    Schibler U (2007) The daily timing of gene expression and physiology in mammals. Dialogues Clin Neurosci 9(3): 257–72PubMedGoogle Scholar
  20. 20.
    Brown SA, Ripperger J, Kadener S et al (2005) PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator. Science 308(5722):693–6CrossRefPubMedGoogle Scholar
  21. 21.
    Guillaumond F, Dardente H, Giguere V, Cermakian N (2005) Differential control of Bmal1 circadian transcription by REV-ERB and ROR nuclear receptors. J Biol Rhythms 20(5):391–403CrossRefPubMedGoogle Scholar
  22. 22.
    Preitner N, Damiola F, Lopez-Molina L et al (2002) The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell 110(2):251–60CrossRefPubMedGoogle Scholar
  23. 23.
    Ueda HR, Chen W, Adachi A et al (2002) A transcription factor response element for gene expression during circadian night. Nature 418(6897):534–9CrossRefPubMedGoogle Scholar
  24. 24.
    Vanselow K, Kramer A (2007) Role of phosphorylation in the mammalian circadian clock. Cold Spring Harbor Symp Quant Biology 72:167–76CrossRefGoogle Scholar
  25. 25.
    Virshup DM, Eide EJ, Forger DB, Gallego M, Harnish EV (2007) Reversible protein phosphorylation regulates circadian rhythms. Cold Spring Harbor Symp Quant Biol 72:413–20CrossRefPubMedGoogle Scholar
  26. 26.
    Toh KL, Jones CR, He Y et al (2001) An hPer2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science 291(5506):1040–3CrossRefPubMedGoogle Scholar
  27. 27.
    Vanselow K, Vanselow JT, Westermark PO et al (2006) Differential effects of PER2 phosphorylation: molecular basis for the human familial advanced sleep phase syndrome (FASPS). Genes Dev 20(19):2660–72CrossRefPubMedGoogle Scholar
  28. 28.
    Xu Y, Toh KL, Jones CR, Shin JY, Fu YH, Ptacek LJ (2007) Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell 128(1):59–70CrossRefPubMedGoogle Scholar
  29. 29.
    Eide EJ, Kang H, Crapo S, Gallego M, Virshup DM (2005) Casein kinase I in the mammalian circadian clock. Methods Enzymol 393:408–18CrossRefPubMedGoogle Scholar
  30. 30.
    Lee C, Etchegaray JP, Cagampang FR, Loudon AS, Reppert SM (2001) Posttranslational mechanisms regulate the mammalian circadian clock. Cell 107(7):855–67CrossRefPubMedGoogle Scholar
  31. 31.
    Sanada K, Harada Y, Sakai M, Todo T, Fukada Y (2004) Serine phosphorylation of mCRY1 and mCRY2 by mitogen-activated protein kinase. Genes Cells 9(8):697–708CrossRefPubMedGoogle Scholar
  32. 32.
    Yin L, Wang J, Klein PS, Lazar MA (2006) Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock. Science 311(5763):1002–5CrossRefPubMedGoogle Scholar
  33. 33.
    Asher G, Gatfield D, Stratmann M et al (2008) SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134(2):317–28CrossRefPubMedGoogle Scholar
  34. 34.
    Hirayama J, Sahar S, Grimaldi B et al (2007) CLOCK-mediated acetylation of BMAL1 controls circadian function. Nature 450(7172):1086–90CrossRefPubMedGoogle Scholar
  35. 35.
    Cardone L, Hirayama J, Giordano F, Tamaru T, Palvimo JJ, Sassone-Corsi P (2005) Circadian clock control by SUMOylation of BMAL1. Science 309(5739):1390–4CrossRefPubMedGoogle Scholar
  36. 36.
    Liu AC, Welsh DK, Ko CH et al (2007) Intercellular coupling confers robustness against mutations in the SCN circadian clock network. Cell 129(3):605–16CrossRefPubMedGoogle Scholar
  37. 37.
    Nagoshi E, Saini C, Bauer C, Laroche T, Naef F, Schibler U (2004) Circadian gene expression in individual fibroblasts: cell-autonomous and self-sustained oscillators pass time to daughter cells. Cell 119(5):693–705CrossRefPubMedGoogle Scholar
  38. 38.
    Welsh DK, Yoo SH, Liu AC, Takahashi JS, Kay SA (2004) Bioluminescence imaging of individual fibroblasts reveals persistent, independently phased circadian rhythms of clock gene expression. Curr Biol 14(24):2289–95CrossRefPubMedGoogle Scholar
  39. 39.
    Indic P, Schwartz WJ, Herzog ED, Foley NC, Antle MC (2007) Modeling the behavior of coupled cellular circadian oscillators in the suprachiasmatic nucleus. J Biol Rhythms 22(3):211–9CrossRefPubMedGoogle Scholar
  40. 40.
    Guo H, Brewer JM, Lehman MN, Bittman EL (2006) Suprachiasmatic regulation of circadian rhythms of gene expression in hamster peripheral organs: effects of transplanting the pacemaker. J Neurosci 26(24):6406–12CrossRefPubMedGoogle Scholar
  41. 41.
    Ralph MR, Foster RG, Davis FC, Menaker M (1990) Transplanted suprachiasmatic nucleus determines circadian period. Science 247(4945):975–8CrossRefPubMedGoogle Scholar
  42. 42.
    Yoo SH, Yamazaki S, Lowrey PL et al (2004) PERIOD2:: LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. Proc Natl Acad Sci U S A 101(15): 5339–46CrossRefPubMedGoogle Scholar
  43. 43.
    Balsalobre A, Brown SA, Marcacci L et al (2000) Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science 289(5488):2344–7CrossRefPubMedGoogle Scholar
  44. 44.
    Balsalobre A, Marcacci L, Schibler U (2000) Multiple signaling pathways elicit circadian gene expression in cultured Rat-1 fibroblasts. Curr Biol 10(20):1291–4CrossRefPubMedGoogle Scholar
  45. 45.
    Le Minh N, Damiola F, Tronche F, Schutz G, Schibler U (2001) Glucocorticoid hormones inhibit food-induced phase-shifting of peripheral circadian oscillators. EMBO J 20(24):7128–36CrossRefPubMedGoogle Scholar
  46. 46.
    Reddy AB, Maywood ES, Karp NA et al (2007) Glucocorticoid signaling synchronizes the liver circadian transcriptome. Hepatology 45(6):1478–88CrossRefPubMedGoogle Scholar
  47. 47.
    McNamara P, Seo SB, Rudic RD, Sehgal A, Chakravarti D, FitzGerald GA (2001) Regulation of CLOCK and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock. Cell 105(7):877–89CrossRefPubMedGoogle Scholar
  48. 48.
    Shirai H, Oishi K, Ishida N (2006) Bidirectional CLOCK/BMAL1-dependent circadian gene regulation by retinoic acid in vitro. Biochem Biophys Res Commun 351(2): 387–91CrossRefPubMedGoogle Scholar
  49. 49.
    Akashi M, Nishida E (2000) Involvement of the MAP kinase cascade in resetting of the mammalian circadian clock. Genes Dev 14(6):645–9PubMedGoogle Scholar
  50. 50.
    Yagita K, Tamanini F, van Der Horst GT, Okamura H (2001) Molecular mechanisms of the biological clock in cultured fibroblasts. Science 292(5515):278–81CrossRefPubMedGoogle Scholar
  51. 51.
    Kon N, Hirota T, Kawamoto T, Kato Y, Tsubota T, Fukada Y (2008) Activation of TGF-beta/activin signalling resets the circadian clock through rapid induction of Dec1 transcripts. Nat Cell Biol 10(12):1463–9CrossRefPubMedGoogle Scholar
  52. 52.
    Koinuma S, Yagita K, Fujioka A, Takashima N, Takumi T, Shigeyoshi Y (2009) The resetting of the circadian rhythm by Prostaglandin J(2) is distinctly phase-dependent. FEBS Lett 583:413–418CrossRefPubMedGoogle Scholar
  53. 53.
    Nakahata Y, Akashi M, Trcka D, Yasuda A, Takumi T (2006) The in vitro real-time oscillation monitoring system identifies potential entrainment factors for circadian clocks. BMC Mol Biol 7:5CrossRefPubMedGoogle Scholar
  54. 54.
    Tsuchiya Y, Minami I, Kadotani H, Nishida E (2005) Resetting of peripheral circadian clock by prostaglandin E2. EMBO Rep 6(3):256–61CrossRefPubMedGoogle Scholar
  55. 55.
    Yagita K, Okamura H (2000) Forskolin induces circadian gene expression of rPer1, rPer2 and dbp in mammalian rat-1 fibroblasts. FEBS Lett 465(1):79–82CrossRefPubMedGoogle Scholar
  56. 56.
    Takashima N, Fujioka A, Hayasaka N, Matsuo A, Takasaki J, Shigeyoshi Y (2006) Gq/11-induced intracellular calcium mobilization mediates Per2 acute induction in Rat-1 fibroblasts. Genes Cells 11(9):1039–49CrossRefPubMedGoogle Scholar
  57. 57.
    Hirota T, Okano T, Kokame K, Shirotani-Ikejima H, Miyata T, Fukada Y (2002) Glucose down-regulates Per1 and Per2 mRNA levels and induces circadian gene expression in cultured Rat-1 fibroblasts. J Biol Chem 277(46):44244–51CrossRefPubMedGoogle Scholar
  58. 58.
    Masumoto KH, Fujioka A, Nakahama K, Inouye ST, Shigeyoshi Y (2003) Effect of phosphodiesterase type 4 on circadian clock gene Per1 transcription. Biochem Biophys Res Commun 306(3):781–5CrossRefPubMedGoogle Scholar
  59. 59.
    Qu Y, Mao M, Li X et al (2008) Telomerase reconstitution contributes to resetting of circadian rhythm in fibroblasts. Mol Cell Biochem 313(1–2):11–8CrossRefPubMedGoogle Scholar
  60. 60.
    Meng QJ, McMaster A, Beesley S et al (2008) Ligand modulation of REV-ERBalpha function resets the peripheral circadian clock in a phasic manner. J Cell Sci 121(Pt 21): 3629–35CrossRefPubMedGoogle Scholar
  61. 61.
    Brown SA, Zumbrunn G, Fleury-Olela F, Preitner N, Schibler U (2002) Rhythms of mammalian body temperature can sustain peripheral circadian clocks. Curr Biol 12(18):1574–83CrossRefPubMedGoogle Scholar
  62. 62.
    Oklejewicz M, Destici E, Tamanini F, Hut RA, Janssens R, van der Horst GT (2008) Phase resetting of the mammalian circadian clock by DNA damage. Curr Biol 18(4):286–91CrossRefPubMedGoogle Scholar
  63. 63.
    Konturek SJ, Konturek JW, Pawlik T, Brzozowski T (2004) Brain-gut axis and its role in the control of food intake. J Physiol Pharmacol 55(1 Pt 2):137–54PubMedGoogle Scholar
  64. 64.
    Rutter J, Reick M, Wu LC, McKnight SL (2001) Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science 293(5529):510–4CrossRefPubMedGoogle Scholar
  65. 65.
    Nakahata Y, Kaluzova M, Grimaldi B et al (2008) The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 134(2):329–40CrossRefPubMedGoogle Scholar
  66. 66.
    Zschoernig B, Mahlknecht U (2008) SIRTUIN 1: regulating the regulator. Biochem Biophys Res Commun 376(2): 251–5CrossRefPubMedGoogle Scholar
  67. 67.
    Lightman SL (2008) The neuroendocrinology of stress: a never ending story. J Neuroendocrinol 20(6):880–4CrossRefPubMedGoogle Scholar
  68. 68.
    Fukumoto S (2008) Actions and mode of actions of FGF19 subfamily members. Endocrine J 55(1):23–31CrossRefGoogle Scholar
  69. 69.
    Lundasen T, Galman C, Angelin B, Rudling M (2006) Circulating intestinal fibroblast growth factor 19 has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man. J Intern Med 260(6):530–6CrossRefPubMedGoogle Scholar
  70. 70.
    Galman C, Lundasen T, Kharitonenkov A et al (2008) The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARalpha activation in man. Cell Metab 8(2):169–74CrossRefPubMedGoogle Scholar
  71. 71.
    Oishi K, Uchida D, Ishida N (2008) Circadian expression of FGF21 is induced by PPARalpha activation in the mouse liver. FEBS Lett 582(25–26):3639–42CrossRefPubMedGoogle Scholar
  72. 72.
    Coskun T, Bina HA, Schneider MA et al (2008) FGF21 corrects obesity in mice. Endocrinology 149:6018–6027CrossRefPubMedGoogle Scholar
  73. 73.
    O’Neill JS, Maywood ES, Chesham JE, Takahashi JS, Hastings MH (2008) cAMP-dependent signaling as a core component of the mammalian circadian pacemaker. Science 320(5878):949–53CrossRefPubMedGoogle Scholar
  74. 74.
    Yang X, Downes M, Yu RT et al (2006) Nuclear receptor expression links the circadian clock to metabolism. Cell 126(4):801–10CrossRefPubMedGoogle Scholar
  75. 75.
    Teboul M, Guillaumond F, Grechez-Cassiau A, Delaunay F (2008) The nuclear hormone receptor family round the clock. Mol Endocrinol 22(12):2573–82CrossRefPubMedGoogle Scholar
  76. 76.
    Yang X, Lamia KA, Evans RM (2007) Nuclear receptors, metabolism, and the circadian clock. Cold Spring Harbor Symp Quant Biol 72:387–94CrossRefPubMedGoogle Scholar
  77. 77.
    Canaple L, Rambaud J, Dkhissi-Benyahya O et al (2006) Reciprocal regulation of brain and muscle Arnt-like protein 1 and peroxisome proliferator-activated receptor alpha defines a novel positive feedback loop in the rodent liver circadian clock. Mol Endocrinol 20(8):1715–27CrossRefPubMedGoogle Scholar
  78. 78.
    Liu C, Li S, Liu T, Borjigin J, Lin JD (2007) Transcriptional coactivator PGC-1alpha integrates the mammalian clock and energy metabolism. Nature 447(7143):477–81CrossRefPubMedGoogle Scholar
  79. 79.
    Bernard O (2007) Lim kinases, regulators of actin dynamics. Int J Biochem Cell Biol 39(6):1071–6CrossRefPubMedGoogle Scholar
  80. 80.
    Posern G, Treisman R (2006) Actin’ together: serum response factor, its cofactors and the link to signal transduction. Trends Cell Biol 16(11):588–96CrossRefPubMedGoogle Scholar
  81. 81.
    Busino L, Bassermann F, Maiolica A et al (2007) SCFFbxl3 controls the oscillation of the circadian clock by directing the degradation of cryptochrome proteins. Science 316 (5826):900–4CrossRefPubMedGoogle Scholar
  82. 82.
    Godinho SI, Maywood ES, Shaw L et al (2007) The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period. Science 316(5826):897–900CrossRefPubMedGoogle Scholar
  83. 83.
    Siepka SM, Yoo SH, Park J et al (2007) Circadian mutant overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression. Cell 129(5):1011–23CrossRefPubMedGoogle Scholar
  84. 84.
    Reischl S, Vanselow K, Westermark PO et al (2007) Beta-TrCP1-mediated degradation of PERIOD2 is essential for circadian dynamics. J Biol Rhythms 22(5):375–86CrossRefPubMedGoogle Scholar
  85. 85.
    Ohsaki K, Oishi K, Kozono Y, Nakayama K, Nakayama KI, Ishida N (2008) The role of beta-TrCP1 and beta-TrCP2 in circadian rhythm generation by mediating degradation of clock protein PER2. J Biochem 144(5):609–18Google Scholar
  86. 86.
    Reinke H, Saini C, Fleury-Olela F, Dibner C, Benjamin IJ, Schibler U (2008) Differential display of DNA-binding proteins reveals heat-shock factor 1 as a circadian transcription factor. Genes Dev 22(3):331–45CrossRefPubMedGoogle Scholar
  87. 87.
    Holmberg CI, Hietakangas V, Mikhailov A et al (2001) Phosphorylation of serine 230 promotes inducible transcriptional activity of heat shock factor 1. EMBO J 20(14): 3800–10CrossRefPubMedGoogle Scholar
  88. 88.
    Katsuki K, Fujimoto M, Zhang XY et al (2004) Feeding induces expression of heat shock proteins that reduce oxidative stress. FEBS Lett 571(1–3):187–91CrossRefPubMedGoogle Scholar
  89. 89.
    Westerheide SD, Bosman JD, Mbadugha BN et al (2004) Celastrols as inducers of the heat shock response and cytoprotection. J Biol Chem 279(53):56053–60CrossRefPubMedGoogle Scholar
  90. 90.
    Chen D, Bruno J, Easlon E et al (2008) Tissue-specific regulation of SIRT1 by calorie restriction. Genes Dev 22(13): 1753–7CrossRefPubMedGoogle Scholar
  91. 91.
    Danno S, Nishiyama H, Higashitsuji H et al (1997) Increased transcript level of RBM3, a member of the glycine-rich RNA-binding protein family, in human cells in response to cold stress. Biochem Biophys Res Commun 236(3):804–7CrossRefPubMedGoogle Scholar
  92. 92.
    Nishiyama H, Itoh K, Kaneko Y, Kishishita M, Yoshida O, Fujita J (1997) A glycine-rich RNA-binding protein mediating cold-inducible suppression of mammalian cell growth. J Cell Biol 137(4):899–908CrossRefPubMedGoogle Scholar
  93. 93.
    Wang X, Arai S, Song X et al (2008) Induced ncRNAs allosterically modify RNA-binding proteins in cis to inhibit transcription. Nature 454(7200):126–30CrossRefPubMedGoogle Scholar
  94. 94.
    Schibler U (2009) Peripheral phase coordination in the mammalian circadian timing system. J Biol Rhythms 24: 3–15CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2010

Authors and Affiliations

  • Ueli Schibler
    • 1
    Email author
  • Gad Asher
    • 1
  • Camille Saini
    • 1
  • Jörg Morf
    • 1
  • Hans Reinke
    • 1
  1. 1.Department of Molecular Biology and National Center of Competence in Research “Frontiers in Genetics”, Sciences IIIUniversity of GenevaGeneva-4Switzerland

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