DEC1 and DEC2—basic helix-loop-helix transcription factors—exhibit a circadian expression in the suprachiasmatic nucleus and other peripheral tissues and seem to play roles in regulating the mammalian circadian rhythm by suppressing the CLOCK/BMAL1-activated promoters of Per1, Dec1, and Dec2. The authors present data on the expression patterns of mRNA for Dec1, Dec2, Per2, Dbp, and Npas2 in various tissues of wild-type and homozygous Clock mutant mice (Clock/Clock). The Clock mutation resulted in extreme reduction of Dec1 expression in kidney, heart, and skeletal muscle but not in liver, whereas it strongly repressed Dec2 expression in liver, kidney, and heart, while Dec2 expression in skeletal muscle remained rhythmic. Per2 also showed the tissue-dependent disruption of the rhythmicity by Clock mutation, whereas rhythmic expression of Dbp in Clock mutant mice disappeared in all tissues examined. Npas2, a structurally and functionally related gene to Clock, showed significant levels of expression in the liver and kidney with a robust rhythmicity, which was also affected by Clock mutation. These marked changes in the Dec1 and Dec2 expression, as well as in the Per2, Dbp, and Npas2 expression in the periphery by Clock mutation, indicated that CLOCK plays a major role in the expression of these genes in most tissues. However, circadian expression of Dec1 in liver and kidney and that of Dec2 in skeletal muscle of Clock mutant mice suggested that CLOCK-independent circadian regulation operates in some tissues.
Balsalobre A, Brown SA, Marcacci L, Tronche F, Kellendonk C, Reichardt HM, Schutz G, and Schibler U (2000) Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science289:2344-2347.
2.
Boudjelal M, Taneja R, Matsubara S, Bouillet P, Dolle P, and Chambon P (1997) Overexpression of Stra13, a novel retinoic acid-inducible gene of the basic helix-loop-helix family, inhibits mesodermal and promotes neuronal differentiation of P19 cells. Genes Dev11:2052-2065.
3.
Butler M, Honma S, Fukumoto T, Kawamoto T, Fujimoto K, Noshiro M, Kato Y, and Honma K (2004) Dec1 and Dec2 expression is disrupted in the suprachiasmatic nuclei of Clock mutant mice. J Biol Rhythms19:126-134.
4.
Daan S and Aschoff J (2001) The entrainment of circadian system. In Handbook of Behavioral Neurobiology: 12. Circadian Clocks, Takahashi JS, Turek FW, Moore RY, eds, pp 7-43, Kluwer Academic/Plenum, New York.
5.
Damiola F, Le Minh N, Preitner N, Kornmann B, Fleury-Olela F, and Schibler U (2000) Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev14:2950-2961.
6.
Fujimoto K, Shen M, Noshiro M, Matsubara K, Shingu S, Honda K, Yoshida E, Suardita K, Matsuda Y, and Kato Y (2001) Molecular cloning and characterization of DEC2, a new member of basic helix-loop-helix proteins. Biochem Biophys Res Commun280:164-171.
7.
Gekakis N, Staknis D, Nguyen HB, Davis FC, Wilsbacher LD, King DP, Takahashi JS, and Weitz CJ (1998). Role of the CLOCK protein in the mammalian circadian mechanism. Science280:1564-1569.
8.
Gibson UE, Heid CA, and Williams PM (1996). A novel method for real time quantitative RT-PCR. Genome Res6:995-1001.
9.
Grechez-Cassiau A, Panda S, Lacoche S, Teboul M, Azmi S, Laudet V, Hogenesch JB, Taneja R, and Delaunay F (2004). The transcriptional repressor STRA13 regulates a subset of peripheral circadian outputs. J Biol Chem279:1141-1150.
10.
Hamaguchi H, Fujimoto K, Kawamoto T, Noshiro M, Maemura K, Takeda N, Nagai R, Furukawa M, Honma S, Honma K, et al. (2004). Expression of the gene for Dec2, a basic helix-loop-helix transcription factor, is regulated by a molecular clock system. Biochem J382:43-50.
11.
Honma S, Kawamoto T, Takagi Y, Fujimoto K, Sato F, Noshiro M, Kato Y, and Honma K (2002). Dec1 and Dec2 are regulators of the mammalian molecular clock. Nature419:841-844.
12.
Ivanova AV, Ivanov SV, Danilkovitch-Miagkova A, and Lerman MI (2001). Regulation of STRA13 by the von Hippel-Lindau tumor suppressor protein, hypoxia, and the UBC9/ubiquitin proteasome degradation pathway. J Biol Chem276:15306-15315.
13.
Jin X, Shearman LP, Weaver DR, Zylka MJ, de Vries GJ, and Reppert SM (1999). A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. Cell96:57-68.
14.
Kawamoto T, Noshiro M, Sato F, Maemura K, Takeda N, Nagai R, Iwata T, Fujimoto K, Furukawa M, Miyazaki K, et al. (2004). A novel autofeedback loop of Dec1 transcription involved in circadian rhythm regulation. Biochem Biophys Res Commun313:117-124.
15.
King DP, Zhao Y, Sangoram AM, Wilsbacher LD, Tanaka M, Antoch MP, Steeves TD, Vitaterna MH, Kornhauser JM, Lowrey PL, et al. (1997). Positional cloning of the mouse circadian clock gene. Cell89:641-653.
16.
Kume K, Zylka MJ, Sriram S, Shearman LP, Weaver DR, Jin X, Maywood ES, Hastings MH, and Reppert SM (1999). mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell98:193-205.
17.
Mitsui S, Yamaguchi S, Matsuo T, Ishida Y, and Okamura H (2001). Antagonistic role of E4BP4 and PAR proteins in the circadian oscillatory mechanism. Genes Dev15:995-1006.
18.
Miyazaki K, Kawamoto T, Tanimoto K, Nishiyama M, Honda H, and Kato Y (2002). Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes. J Biol Chem277:47014-47021.
19.
Nakamura W, Honma S, Shirakawa T, and Honma K (2002). Clock mutation lengthens the circadian period without damping rhythms in individual SCN neurons. Nat Neurosci5:399-400.
20.
Niijima A, Nagai K, Nagai N, and Akagawa H (1993). Effects of light stimulation on the activity of the autonomic nerves in anesthetized rats. Physiol Behav54:555-561.
21.
Noshiro M, Kawamoto T, Furukawa M, Fujimoto K, Yoshida Y, Sasabe E, Tsutsumi S, Hamada T, Honma S, Honma K, et al. (2004). Rhythmic expression of DEC1 and DEC2 in peripheral tissues: DEC2 is a potent suppressor for hepatic cytochrome P450s opposing DBP. Genes Cells9:317-329.
22.
Oishi K, Fukui H, Ishida N, Ikeda M, Yu W, Hirai M, Ebisawa T, Honma S, Yoshimura K, Honma KI, et al. (2000). Rhythmic expression of BMAL1 mRNA is altered in Clock mutant mice: differential regulation in the suprachiasmatic nucleus and peripheral tissues. Biochem Biophys Res Commun268:164-171.
23.
Oishi K, Miyazaki K, and Ishida N (2002). Functional CLOCK is not involved in the entrainment of peripheral clocks to the restricted feeding: entrainable expression of mPer2 and BMAL1 mRNAs in the heart of Clock mutant mice on Jcl:ICR background. Biochem Biophys Res Commun298:198-202.
24.
Oishi K, Miyazaki K, Kadota K, Kikuno R, Nagase T, Atsumi G, Ohkura N, Azama T, Mesaki M, Yukimasa S, et al. (2003). Genome-wide expression analysis of mouse liver reveals CLOCK-regulated circadian output genes. J Biol Chem278:41519-41527.
25.
Panda S, Antoch MP, Miller BH, Su AI, Schook AB, Straume M, Schultz PG, Kay SA, Takahashi JS, and Hogenesch JB (2002). Coordinated transcription of key pathways in the mouse by the circadian clock. Cell109:307-320.
26.
Pittendrigh CS and Daan S (1976). Functional-analysis of circadian pacemakers in nocturnal rodents: IV. Entrainment: pacemaker as clock. J Comp Physiol106:291-331.
27.
Reick M, Garcia JA, Dudley C, and McKnight SL (2001). NPAS2: an analog of clock operative in the mammalian forebrain. Science293:506-509.
28.
Ripperger JA, Shearman LP, Reppert SM, and Schibler U (2000). CLOCK, an essential pacemaker component, controls expression of the circadian transcription factor DBP. Genes Dev14:679-689.
29.
Roenneberg T and Merrow M (2003). The network of time: understanding the molecular circadian system. Curr Biol13:R198-R207.
30.
Rossner MJ, Dorr J, Gass P, Schwab MH, and Nave KA (1997). SHARPs: mammalian enhancer-of-split- and hairy-related proteins coupled to neuronal stimulation. Mol Cell Neurosci10:460-475.
31.
Sakamoto K, Nagase T, Fukui H, Horikawa K, Okada T, Tanaka H, Sato K, Miyake Y, Ohara O, Kako K, et al. (1998). Multitissue circadian expression of rat period homolog (rPer2) mRNA is governed by the mammalian circadian clock, the suprachiasmatic nucleus in the brain. J Biol Chem273:27039-27042.
32.
Sato F, Kawamoto T, Fujimoto K, Noshiro M, Honda KK, Honma S, Honma K, and Kato Y (2004). Functional analysis of the basic helix-loop-helix transcription factor DEC1 in circadian regulation: interaction with BMAL1. Eur J Biochem271:4409-4419.
33.
Shen M, Kawamoto T, Teramoto M, Makihira S, Fujimoto K, Yan W, Noshiro M, and Kato Y (2001). Induction of basic helix-loop-helix protein DEC1 (BHLHB2)/Stra13/Sharp2 in response to the cyclic adenosine monophosphate pathway. Eur J Cell Biol80:329-334.
34.
Shen M, Kawamoto T, Yan W, Nakamasu K, Tamagami M, Koyano Y, Noshiro M, and Kato Y (1997). Molecular characterization of the novel basic helix-loop-helix protein DEC1 expressed in differentiated human embryo chondrocytes. Biochem Biophys Res Commun236:294-298.
35.
Shen M, Yoshida E, Yan W, Kawamoto T, Suardita K, Koyano Y, Fujimoto K, Noshiro M, and Kato Y (2002). Basic helix-loop-helix protein DEC1 promotes chondrocyte differentiation at the early and terminal stages. J Biol Chem277:50112-50120.
36.
Shibata S (2004). Neural regulation of the hepatic circadian rhythm. Anat Rec A Discov Mol Cell Evol Biol280:901-909.
37.
Storch KF, Lipan O, Leykin I, Viswanathan N, Davis FC, Wong WH, and Weitz CJ (2002). Extensive and divergent circadian gene expression in liver and heart. Nature417:78-83.
38.
Sun H, Lu B, Li RQ, Flavell RA, and Taneja R (2001). Defective T cell activation and autoimmune disorder in Stra13-deficient mice. Nat Immunol2:1040-1047.
39.
Sun H and Taneja R (2000). Stra13 expression is associated with growth arrest and represses transcription through histone deacetylase (HDAC)-dependent and HDAC-independent mechanisms. Proc Natl Acad Sci USA97:4058-4063.
40.
Teramoto M, Nakamasu K, Noshiro M, Matsuda Y, Gotoh O, Shen M, Tsutsumi S, Kawamoto T, Iwamoto Y, and Kato Y (2001). Gene structure and chromosomal location of a human bHLH transcriptional factor DEC1/Stra13/SHARP-2/BHLHB2. J Biochem129:391-396
41.
Terazono H, Mutoh T, Yamaguchi S, Kobayashi M, Akiyama M, Udo R, Ohdo S, Okamura H, and Shibata S (2003). Adrenergic regulation of clock gene expression in mouse liver. Proc Natl Acad Sci USA100:6795-6800.
42.
Thomas PS (1980). Hybridization of denatured RNA and small DNA fragments transferred to nitrocellulose. Proc Natl Acad Sci USA77:5201-5205.
43.
Tischkau SA, Mitchell JW, Tyan SH, Buchanan GF, and Gillette MU (2003). Ca2+/cAMP response element-binding protein (CREB)-dependent activation of Per1 is required for light-induced signaling in the suprachiasmatic nucleus circadian clock. J Biol Chem278:718-723.
44.
Travnickova-Bendova Z, Cermakian N, Reppert SM, and Sassone-Corsi P (2002). Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity. Proc Natl Acad Sci USA99:7728-7733.
45.
Ueda HR, Chen W, Adachi A, Wakamatsu H, Hayashi S, Takasugi T, Nagano M, Nakahama K, Suzuki Y, Sugano S, et al. (2002). A transcription factor response element for gene expression during circadian night. Nature418:534-539.
46.
Vitaterna MH, King DP, ChangAM, Kornhauser JM, Lowrey PL, McDonald JD, Dove WF, Pinto LH, Turek FW, and Takahashi JS (1994). Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science264:719-725.
47.
Wuarin J and Schibler U (1990). Expression of the liver-enriched transcriptional activator protein DBP follows a stringent circadian rhythm. Cell63:1257-1266.
48.
Yamada K, Kawata H, Shou Z, Mizutani T, Noguchi T, and Miyamoto K (2003). Insulin induces the expression of the SHARP-2/Stra13/DEC1 gene via a phosphoinositide 3-kinase pathway. J Biol Chem278:30719-30724.
49.
Zhou YD, Barnard M, Tian H, Li X, Ring HZ, Francke U, Shelton J, Richardson J, Russell DW, and McKnight SL (1997). Molecular characterization of two mammalian bHLH-PAS domain proteins selectively expressed in the central nervous system. Proc Natl Acad Sci USA94:713-718.
