Animal cells and systems

The Korean Society for Integrative Biology (한국통합생물학회)
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Posttranslational and epigenetic regulation of the CLOCK/BMAL1 complex in the mammalian

  • Lee, Yool (Seoul National Universisty, School of Biological Sciences) ;
  • Kim, Kyung-Jin (Seoul National Universisty, School of Biological Sciences)
  • Received : 2011.05.18
  • Accepted : 2011.07.05
  • Published : 2012.02.28
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Abstract

Most living organisms synchronize their physiological and behavioral activities with the daily changes in the environment using intrinsic time-keeping systems called circadian clocks. In mammals, the key molecular features of the internal clock are transcription- and translational-based negative feedback loops, in which clock-specific transcription factors activate the periodic expression of their own repressors, thereby generating the circadian rhythms. CLOCK and BMAL1, the basic helix-loop-helix (bHLH)/PAS transcription factors, constitute the positive limb of the molecular clock oscillator. Recent investigations have shown that various levels of posttranslational regulation work in concert with CLOCK/BMAL1 in mediating circadian and cellular stimuli to control and reset the circadian rhythmicity. Here we review how the CLOCK and BMAL1 activities are regulated by intracellular distribution, posttranslational modification, and the recruitment of various epigenetic regulators in response to circadian and cellular signaling pathways.

Keywords

References

  1. Akhtar RA, Reddy AB, Maywood ES, Clayton JD, King VM, Smith AG, Gant TW, Hastings MH, Kyriacou CP. 2002. Circadian cycling of the mouse liver transcriptome, as revealed by cDNA microarray, is driven by the suprachiasmatic nucleus. Curr Biol. 12:540-550.
  2. Asher G, Schibler U. 2011. Crosstalk between components of circadian and metabolic cycles in mammals. Cell Metab. 13:125-137. https://doi.org/10.1016/j.cmet.2011.01.006
  3. Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, Mostoslavsky R, Alt FW, Schibler U. 2008. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell. 134:317-328. https://doi.org/10.1016/j.cell.2008.06.050
  4. Balsalobre A, Damiola F, Schibler U. 1998. A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell. 93:929-937. https://doi.org/10.1016/S0092-8674(00)81199-X
  5. Bass J, Takahashi JS. 2010. Circadian integration of metabolism and energetics. Science. 330:1349-1354. https://doi.org/10.1126/science.1195027
  6. Brown SA, Ripperger J, Kadener S, Fleury-Olela F, Vilbois F, Rosbash M, Schibler U. 2005. PERIOD1-associated proteins modulate the negative limb of the mammalian circadian oscillator. Science. 308:693-696. https://doi.org/10.1126/science.1107373
  7. Bunger MK, Wilsbacher LD, Moran SM, Clendenin C, Radcliffe LA, Hogenesch JB, Simon MC, Takahashi JS, Bradfield CA. 2000. Mop3 is an essential component of the master circadian pacemaker in mammals. Cell. 103:1009-1017. https://doi.org/10.1016/S0092-8674(00)00205-1
  8. Cardone L, Hirayama J, Giordano F, Tamaru T, Palvimo JJ, Sassone-Corsi P. 2005. Circadian clock control by SUMOylation of BMAL1. Science. 309:1390-1394. https://doi.org/10.1126/science.1110689
  9. Cermakian N, Sassone-Corsi P. 2000. Multilevel regulation of the circadian clock. Nat Rev Mol Biol. 1:59-67.
  10. Curtis AM, Seo SB, Westgate EJ, Rudic RD, Smyth EM, Chakravarti D, FitzGerald GA, McNamara P. 2004. Histone acetyltransferase-dependent chromatin remodeling and the Vascular Clock. J Biol Chem. 279:7091-7097. https://doi.org/10.1074/jbc.M311973200
  11. Dardente H, Fortier EE, Martineau V, Cermakian N. 2007. Cryptochromes impair phosphorylation of transcriptional activators in the clock: A general mechanism for circadian repression. Biochem J. 402:525-536. https://doi.org/10.1042/BJ20060827
  12. Dibner C, Schibler U, Albrecht U. 2010. The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol. 72:517-549. https://doi.org/10.1146/annurev-physiol-021909-135821
  13. Doi M, Hirayama J, Sassone-Corsi P. 2006. Circadian regulator CLOCK is a histone acetyltransferase. Cell. 125:497-508. https://doi.org/10.1016/j.cell.2006.03.033
  14. 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. 12:551-557. https://doi.org/10.1016/S0960-9822(02)00765-0
  15. Duguay D, Cermakian N. 2009. The crosstalk between physiology and circadian clock proteins. Chronobiol Int. 26:1479-1513. https://doi.org/10.3109/07420520903497575
  16. Eckel-Mahan K, Sassone-Corsi P. 2009. Metabolism control by the circadian clock and vice versa. Nat Struct Mol Biol. 16:462-467. https://doi.org/10.1038/nsmb.1595
  17. Eide EJ, Vielhaber EL, Hinz WA, Virshup DM. 2002. The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase I$\varepsilon$. J Biol Chem. 277:17248-17254. https://doi.org/10.1074/jbc.M111466200
  18. Etchegaray JP, Lee C, Wade PA, Reppert SM. 2003. Rhythmic histone acetylation underlies transcription in the mammalian circadian clock. Nature. 421:117-182. https://doi.org/10.1038/421117a
  19. Gallego M, Virshup DM. 2007. Post-translational modifications regulate the ticking of the circadian clock. Nat Cell Biol. 8:139-148. https://doi.org/10.1038/nrm2106
  20. Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP, Takahashi JS, Weitz CJ. 1998. Role of the CLOCK protein in the mammalian circadian mechanism. Science. 280:1564-1569. https://doi.org/10.1126/science.280.5369.1564
  21. Gu YZ, Hogenesch JB, Bradfield CA. 2000. The PAS superfamily: sensors of environmental and developmental signals. Annu Rev Pharmacol Toxicol. 40:519-556. https://doi.org/10.1146/annurev.pharmtox.40.1.519
  22. Hirayama J, Sahar S, Grimaldi B, Tamaru T, Takamatsu K, Nakahata Y, Sassone-Corsi P. 2007. CLOCK-mediated acetylation of BMAL1 controls circadian function. Nature. 450:1086-1090. https://doi.org/10.1038/nature06394
  23. Hogenesch JB, Chan WK, Jackiw VH, Brown RC, Gu YZ, Pray-Grant M, Perdew GH, Bradfield CA. 1997. Characterization of a subset of the basic-helix-loop-helix-PAS superfamily that interacts with components of the dioxin signaling pathway. J Biol Chem. 272:8581-8593. https://doi.org/10.1074/jbc.272.13.8581
  24. Hogenesch JB, Gu YX, Jain S, Bradfield CA. 1998. The basic-helix-loophelix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc Natl Acad Sci USA. 95:5474-5479. https://doi.org/10.1073/pnas.95.10.5474
  25. Ikeda M, Nomura M. 1997. cDNA cloning and tissuespecific expression of a novel basic helix-loop-helix/PAS protein (BMAL1) and identification of alternatively spliced variants with alternative translation initiation site usage. Biochem Biophys Res Commun. 233:258-264. https://doi.org/10.1006/bbrc.1997.6371
  26. Jung H, Choe Y, Kim H, Park N, Son GH, Khang I, Kim K. 2003. Involvement of CLOCK:BMAL1 heterodimer in serum-responsive mPer1 induction. Neuroreport. 14:15-19. https://doi.org/10.1097/00001756-200301200-00003
  27. Kalamvoki M, Roizman B. 2010. Circadian CLOCK histone acetyl transferase localizes at ND10 nuclear bodies and enables herpes simplex virus gene expression. Proc Natl Acad Sci USA. 107:17721-17726. https://doi.org/10.1073/pnas.1012991107
  28. Kalkhoven E. 2004. CBP and p300: HATs for different occasions. Biochem Pharmacol. 68:1145-1155. https://doi.org/10.1016/j.bcp.2004.03.045
  29. Katada S, Sassone-Corsi P. 2010. The histone methyltransferase MLL1 permits the oscillation of circadian gene expression. Nat Struct Mol Biol. 17:1414-1421. https://doi.org/10.1038/nsmb.1961
  30. King DP, Zhao Y, Sangoram AM, Wilsbacher LD, Tanaka M, Antoch MP, Steeves TD, Vitaterna MH, Kornhauser JM, Lowrey PL, Turek FW, Takahashi JS. 1997. Positional cloning of the mouse circadian clock gene. Cell. 89:641-653. https://doi.org/10.1016/S0092-8674(00)80245-7
  31. Kiyohara YB, Tagao S, Tamanini F, Morita A, Sugisawa Y, Yasuda M, Yamanaka I, Ueda HR, van der Horst GT, Kondo T, Yagita K. 2006. The BMAL1 C terminus regulates the circadian transcription feedback loop. Proc Natl Acad Sci USA. 103:10074-10079. https://doi.org/10.1073/pnas.0601416103
  32. Klose RJ, Zhang Y. 2007. Regulation of histone methylation by demethylimination and demethylation. Nat Rev Mol Cell Biol. 8:307-318. https://doi.org/10.1038/nrm2143
  33. Kondratov RV, Antoch MP. 2007. The clock proteins, aging, and tumorigenesis. Cold Spring Harb Symp Quant Biol. 72:477-482. https://doi.org/10.1101/sqb.2007.72.050
  34. Kondratov RV, Chernov MV, Kondratova AA, Gorbacheva VY, Gudkov AV, Antoch MP. 2003. BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system. Genes Dev. 17:1921-1932. https://doi.org/10.1101/gad.1099503
  35. Kondratov RV, Kondratova AA, Gorbacheva VY, Vykhovanets OV, Antoch MP. 2006a. Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock. Genes Dev. 20:1868-1873. https://doi.org/10.1101/gad.1432206
  36. Kondratov RV, Kondratova AA, Lee C, Gorbacheva VY, Chernov MV, Antoch MP. 2006b. Post-translational regulation of circadian transcriptional CLOCK(NPAS2)/ BMAL1 complex by CRYPTOCHROMES. Cell Cycle. 5:890-895. https://doi.org/10.4161/cc.5.8.2684
  37. Kouzarides T. 2002. Histone methylation in transcriptional control. Curr Opin Genet Dev. 12:198-209. https://doi.org/10.1016/S0959-437X(02)00287-3
  38. Kwon I, Lee J, Chang SH, Jung NC, Lee BJ, Son GH, Kim K, Lee KH. 2006. BMAL1 shuttling controls transactivation and degradation of the CLOCK/BMAL1 heterodimer. Mol Cell Biol. 26:7318-7330. https://doi.org/10.1128/MCB.00337-06
  39. Lee C, Etchegaray JP, Cagampang FR, Loudon AS, Reppert SM. 2001. Posttranslational mechanisms regulate the mammalian circadian clock. Cell. 107:855-867. https://doi.org/10.1016/S0092-8674(01)00610-9
  40. Lee J, Lee Y, Lee MJ, Park E, Kang SH, Chung CH, Lee KH, Kim K. 2008. Dual modification of BMAL1 by SUMO2/3 and ubiquitin promotes circadian activation of the CLOCK/BMAL1 complex. Mol Cell Biol. 28:6056-6065. https://doi.org/10.1128/MCB.00583-08
  41. Lee Y, Lee J, Kwon I, Nakajima Y, Ohmiya Y, Son GH, Lee KH, Kim K. 2010. Coactivation of the CLOCK-BMAL1 complex by CBP mediates resetting of the circadian clock. J Cell Sci. 123:3547-3557. https://doi.org/10.1242/jcs.070300
  42. Lowrey PL, Shimomura K, Antoch MP, Yamazaki S, Zemenides PD, Ralph MR, Menaker M, Takahashi JS. 2000. Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau. Science. 288:483-492. https://doi.org/10.1126/science.288.5465.483
  43. Marcheva B, Ramsey KM, Buhr ED, Kobayashi Y, Su H, Ko CH, Ivanova G, Omura C, Mo S, Vitaterna MH, Lopez JP, Philipson LH, Bradfield CA, Crosby SD, JeBailey L, Wang X, Takahashi JS, Bass J. 2010. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature. 466:627-631. https://doi.org/10.1038/nature09253
  44. McCarthy JJ, Andrews JL, McDearmon EL, Campbell KS, Barber BK, Miller BH, Walker JR, Hogenesch JB, Takahashi JS, Esser KA. 2007. Identification of the circadian transcriptome in adult mouse skeletal muscle. Physiol Genomics. 31:86-95. https://doi.org/10.1152/physiolgenomics.00066.2007
  45. Mehra A, Baker CL, Loros JJ, Dunlap JC. 2009. Posttranslational modifications in circadian rhythms. Trends Biochem Sci. 34:483-490. https://doi.org/10.1016/j.tibs.2009.06.006
  46. Miller BH, McDearmon EL, Panda S, Hayes KR, Zhang J, Andrews JL, Antoch MP, Walker JR, Esser KA, Hogenesch JB, Takahashi JS. 2007. Circadian and CLOCK-controlled regulation of the mouse transcriptome and cell proliferation. Proc Natl Acad Sci USA. 104:3342-3347. https://doi.org/10.1073/pnas.0611724104
  47. Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D, Guarente LP, Sassone-Corsi P. 2008. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell. 134:329-340. https://doi.org/10.1016/j.cell.2008.07.002
  48. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone- Corsi P. 2009. Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science. 324:654-657. https://doi.org/10.1126/science.1170803
  49. Naruse Y, Oh-hashi K, Iijima N, Naruse M, Yoshioka H, Tanaka M. 2004. Circadian and light induced transcription of clock gene Per1 depends on histone acetylation and deacetylation. Mol Cell Biol. 24:6278-6287. https://doi.org/10.1128/MCB.24.14.6278-6287.2004
  50. Oishi K, Miyazaki K, Kadota K, Kikuno R, Nagase T, Atsumi G, Ohkura N, Azama T, Mesaki M, Yukimasa S, Kobayashi H, Iitaka C, Umehara T, Horikoshi M, Kudo T, Shimizu Y, Yano M, Monden M, Machida K, Matsuda J, Horie S, Todo T, Ishida N. 2003. Genomewide expression analysis of mouse liver reveals CLOCKregulated circadian output genes. J Biol Chem. 278:41519-41527. https://doi.org/10.1074/jbc.M304564200
  51. Panda S, Antoch MP, Miller BH, Su AI, Schook AB, Straume M, Schultz PG, Kay SA, Takahashi JS, Hogenesch JB. 2002. Coordinated transcription of key pathways in the mouse by the circadian clock. Cell. 109:307-20. https://doi.org/10.1016/S0092-8674(02)00722-5
  52. Ramsey KM, Yoshino J, Brace CS, Abrassart D, Kobayashi Y, Marcheva B, Hong HK, Chong JL, Buhr ED, Lee C, Takahashi JS, Imai S, Bass J. 2009. Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science. 324:651-654. https://doi.org/10.1126/science.1171641
  53. Reppert SM, Weaver DR. 2002. Coordination of circadian timing in mammals. Nature. 418:935-941. https://doi.org/10.1038/nature00965
  54. Ripperger JA, Schibler U. 2006. Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drivescircadian DBP transcription and chromatin transitions. Nat Genet. 38:369-374. https://doi.org/10.1038/ng1738
  55. Ripperger JA, Shearman LP, Reppert SM, Schibler U. 2000. CLOCK, an essential pacemaker component, controls expression of the circadian transcription factor DBP. Genes Dev. 14:679-689.
  56. Robles MS, Boyault C, Knutti D, Padmanabhan K, Weitz CJ. 2010. Identification of RACK1 and protein kinase Calpha as integral components of the mammalian circadian clock. Science. 327:463-466. https://doi.org/10.1126/science.1180067
  57. Rutter J, Reick M, Wu LC, McKnight SL. 2001. Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science. 293:510-514. https://doi.org/10.1126/science.1060698
  58. Sahar S, Zocchi L, Kinoshita C, Borrelli E, Sassone-Corsi P. 2010. Regulation of BMAL1 protein stability and circadian function by GSK3beta-mediated phosphorylation. PLoS One. 5:e:8561. https://doi.org/10.1371/journal.pone.0008561
  59. Sanada K, Okano T, Fukada Y. 2002. Mitogen-activated protein kinase phosphorylates and negatively regulates basic helix-loop-helix-PAS transcription factor BMAL1. J Biol Chem. 277:267-271. https://doi.org/10.1074/jbc.M107850200
  60. Santos-Rosa H, Schneider R, Bannister AJ, Sherriff J, Bernstein BE, Emre NC, Schreiber SL, Mellor J, Kouzarides T. 2002. Active genes are tri-methylated at K4 of histone H3. Nature. 419:407-411. https://doi.org/10.1038/nature01080
  61. Sato TK, Yamada RG, Ukai H, Baggs JE, Miraglia LJ, Kobayashi TJ, Welsh DK, Kay SA, Ueda HR, Hogenesch JB. 2006. Feedback repression is required for mammalian circadian clock function. Nat Genet. 38:312-319. https://doi.org/10.1038/ng1745
  62. Schibler U, Sassone-Corsi P. 2002. A web of circadian pacemakers. Cell. 111:919-922. https://doi.org/10.1016/S0092-8674(02)01225-4
  63. Schneider R, Bannister AJ, Myers FA, Thorne AW, Crane-Robinson C, Kouzarides T. 2004. Histone H3 lysine 4 methylation patterns in higher eukaryotic genes. Nat Cell Biol. 6:73-77. https://doi.org/10.1038/ncb1076
  64. Shearman LP, Sriram S, Weaver DR, Maywood ES, Chaves I, Zheng B, Kume K, Lee CC, van der Horst GT, Hastings MH, Reppert SM. 2000. Interacting molecular loops in the mammalian circadian clock. Science. 288:1013-1019. https://doi.org/10.1126/science.288.5468.1013
  65. Shim HS, Kim H, Lee J, Son GH, Cho S, Oh TH, Kang SH, Seen DS, Lee KH, Kim K. 2007. Rapid activation of CLOCK by Ca2+-dependent protein kinase C mediates resetting of the mammalian circadian clock. EMBO Reports. 8:366-371. https://doi.org/10.1038/sj.embor.7400920
  66. Spengler ML, Kuropatwinski KK, Schumer M, Antoch MP. 2009. A serine cluster mediates BMAL1-dependent CLOCK phosphorylation and degradation. Cell Cycle. 8:4138-4146. https://doi.org/10.4161/cc.8.24.10273
  67. Stratmann M, Schibler U. 2006. Properties, entrainment, and physiological functions of mammalian peripheral oscillators. J Biol Rhythms. 21:494-506. https://doi.org/10.1177/0748730406293889
  68. Takahata S, Ozaki T, Mimura J, Kikuchi Y, Sogawa K, Fujii-Kuriyama Y. 2000. Transactivation mechanisms of mouse clock transcription factors, mClock and mArnt3. Genes Cells. 5:739-747. https://doi.org/10.1046/j.1365-2443.2000.00363.x
  69. Tamaru T, Isojima Y, van der Horst GT, Takei K, Nagai K, Takamatsu K. 2003. Nucleocytoplasmic shuttling and phosphorylation of BMAL1 are regulated by circadian clock in cultured fibroblasts. Genes Cells. 8:973-983. https://doi.org/10.1046/j.1365-2443.2003.00686.x
  70. Tamaru T, Hirayama J, Isojima Y, Nagai K, Norioka S, Takamatsu K, Sassone-Corsi P. 2009. CK2alpha phosphorylates BMAL1 to regulate the mammalian clock. Nat Struct Mol Biol. 16:446-448. https://doi.org/10.1038/nsmb.1578
  71. Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, Laposky A, Losee-Olson S, Easton A, Jensen DR, Eckel RH, Takahashi JS, Bass J. 2005. Obesity and metabolic syndrome in circadian Clock mutant mice. Science. 308:1043-1045. https://doi.org/10.1126/science.1108750
  72. Vaissiere T, Sawan C, Herceg Z. 2008. Epigenetic interplay between histone modifications and DNA methylation in gene silencing. Mutat Res. 659:40-48. https://doi.org/10.1016/j.mrrev.2008.02.004
  73. Vitaterna MH, King DP, Chang AM, Kornhauser JM, Lowrey PL, McDonald JD, Dove WF, Pinto LH, Turek FW, Takahashi JS. 1994. Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science. 264:719-725. https://doi.org/10.1126/science.8171325
  74. Vo N, Goodman RH. 2001. CREB-binding protein and p300 in transcriptional regulation. J Biol Chem. 276:13505-13508. https://doi.org/10.1074/jbc.R000025200
  75. Wijnen H, Young MW. 2006. Interplay of circadian clocks and metabolic rhythms. Annu Rev Genet. 40:409-48. https://doi.org/10.1146/annurev.genet.40.110405.090603
  76. Yoshitane H, Takao T, Satomi Y, Du NH, Okano T, Fukada Y. 2009. Roles of CLOCK phosphorylation in suppression of E-box-dependent transcription. Mol Cell Biol. 29:3675-3686. https://doi.org/10.1128/MCB.01864-08
  77. Yujnovsky I, Hirayama J, Doi M, Borrelli E, Sassone-Corsi P. 2006. Signaling mediated by the dopamine D2 receptor potentiates circadian regulation by CLOCK:BMAL1. Proc Natl Acad Sci USA. 103:6386-6391. https://doi.org/10.1073/pnas.0510691103
  78. Zhao WN, Malinin N, Yang FC, Staknis D, Gekakis N, Maier B, Reischl S, Kramer A, Weitz CJ. 2007. CIPC is a mammalian circadian clock protein without invertebrate homologues. Nat Cell Biol. 9:268-275. https://doi.org/10.1038/ncb1539
  79. Zhong S, Salomoni P, Pandolfi PP. 2000. The transcriptional role of PML and the nuclear body. Nat Cell Biol. 2:E85-90. https://doi.org/10.1038/35010583

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