Advance in circadian rhythm genetics in mammals

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1 Chinese Bulletin of Life Sciences Vol. 16, No. 2 Apr., (2004) , Q41 A Advance in circadian rhythm genetics in mammals XU Zu-Yuan 1,2 (1 Beijing Genomics Institute, Institute of Genetics and Developmental Biology,Chinese Academy of Sciences, Beijing , China; 2 College of Life Science, Yangtze University, Jingzhou , China) Abstract: The circadian clock is a self-sustaining oscillator that has a period of about 24 hours and can synchronize itself to changing environmental conditionals to optimize an organisms performance. Besides their own regulation, clock genes can influence biochemical processes by modulating specific genes of biochemical pathways. Developments in the last few years using genetics and molecular biological tools have led to a new understanding of the molecular basis of the circadian clock in mammals. We review here these advances and the prospects for using the homologues as candidate genes in studies of human disorders in the circadian timing system. Key words: circadian rhythm; clock genes; entrainment; clock-controlled genes 24 (central clock) (SCN) 30 (entrainment) (1967 )

2 105 (CACGTG) [5] 1 ( ) 1.1 period 1971 Konopka [1] period (d) 1984 d period 1997 ( m, h) [2~4] period (m1 m3) iod E PER bhlh/pas E bhlh/pas m1 m3 [6~9] m1 mcry1 mrna SCN m1 mcry1 m3 m1 m1 m3 m3 -/- m1 mcry1 mrna m3 1.2 Cryptochrome Cry (mcry1 mcry2) SCN mcry1 RNA [10~13] mcry2 SCN m1 1 mcry1 mcry2 mcry1 -/- 24 mcry2 -/- 24 mcry1/mcry2 SCN m1 [12] mcry1 mcry2 mcry (mcry1 mcry2) -E mcry mper mper [13] 1.3 clock 1997 [14~15] 5 100kb 24 bhlh/pas( - - /PAS) 19 5' 3 A-T m E m - 19 m : m [16] 1.4 m (MOP3) [16~18] m SCN m1 mdbp (D ) m [18] CYCLE BMAL2(Mop9) 1.5 CK1ε 1988 [19] tau (CK1ε) [20~21] CK1ε ddbt PER PER NPAS2(MOP4) [22]

3 106 NPAS2 m1 mcry1 NPAS2 mrna dtim mtim 2 / CRY [23] bhlh-pas m1 m3 mcry1 mcry2 dclock m [15,18] mpers (mper1 mper2 mper3) mcrys (mcry1 mcry2) mper2 (mper1 mper3 ) mcrys / ms mcrys mper2 m [13] m1 mcry1 (M- ), mcry2 (E- ) M-E m1 [6] 3 (entrainment) ( ) 3.1 / CRYs [26] Ca [24] mpers mpers CK1ε mcrys m, m mper2 mcry1 mcry2 m1 (m1 CT4~6 CT9~12) Daan [25] M-E ( ) SCN 1 2 Cry1 Cry2 Cry1/ Cry2 CREB MAP [27] 3.2 / 16 [29] Balsalobre [28]

4 [34] (retinoic acid) McNamara [30] RARα / Rev-erbα Rev-erbβ MOP4/ h1 Rev-erbα -6 camp CREB MAP DBP E4BP4 -α [31] 5 [32] Tau 4 (output pathways) [33] Panda EST 650 ( [34] (DSPS) 24 - (ASPS) [35] 80~ ~ ~85 [33] ( 24 ) 2001 Toh [36] (ASPS) 4 19: h2 A-G CK1ε CK1ε hclock [37] 21~28 5%

5 108 [1] Konopka R J, Benzer S. Clock mutants of Drosophila melanogaster. Proc Natl Acad Sci USA, 1971, 68: 2112~2116 [2] Sun Z S, Albrecht U, Zhuchenko O, et al. RIGUI, a putative mammalian ortholog of the Drosophila period gene. Cell, 1997, 90: 1003~1011 [3] Albrecht U, Sun Z S, Eichele G, et al. A differential response of two putative mammalian circadian regulators, m1 and, to light. Cell, 1997, 91: 1055~1064 [4] Tei H, Okamura H, Shigeyoshi Y, et al. Circadian oscillation of a mammalian homologue of the Drosophila period gene. Nature, 1997, 389: 512~516 [5] Hao H P, Allen D L, Hardin P E. A circadian enhancer mediates PER-dependent mrna cycling in Drosophila melanogaster. Mol Cell Biol, 1997, 17: 3687~3693 [6] Zheng B H, Albrecht U, Kaasik K, et al. Nonredundant roles of the m1 and genes in the mammalian circadian clock. Cell, 2001, 105(5): 683~694 [7] Zylka M J, Shearman L P, Weaver D R, et al. Three period homologs in mammals: differential light responses in the suprachiasmatic circadian clock and oscillating transcripts outside of brain. Neuron, 1998, 20: 1103~1110 [8] Bae K, Jin X W, Maywood E S, et al. Differential functions of m1,, and m3 in the SCN circadian clock. Neuron, 2001, 30(2): 525~536 [9] Shearman L P, Jin X W, Lee C, et al. Targeted disruption of the m3 gene: subtle effects on circadian clock function. Mol Cell Biol, 2000, 20: 6269~6275 [10] Hsu D S, Zhao X D, Zhao Y, et al. A putative human bluelight photoreceptors hcry1 and hcry2 are flavoproteins. Biochemistry, 1996, 35(14): 13871~13877 [11] van der Horst G T J, Muijtjens M, Kobayashi K, et al. Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature, 1999, 398: 627~630 [12] Okamura H, Miyake S, Sumi Y, et al. Photic induction of m1 and in Cry-deficient mice lacking a biological clock. Science, 1999, 286: 2531~2534 [13] Kume K, Zylka M J, Sriram S, et al. mcry1 and mcry2 are essential components of the negative limb of the circadian clock feedback loop. Cell, 98(2): 193~205 [14] Vitaterna M H, King D P, Chang A M, et al. Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science, 1994, 264: 719~725 [15] King D P, Zhao Y L, Sangoram A M, et al. Positional cloning of the mouse circadian clock gene. Cell, 1997, 89(4): 641~653 [16] Gekakis N, Staknis D, Nguyen H B, et al. Role of the protein in the mammalian circadian mechanism. Science, 1998, 280: 1564~1569 [17] Hogenesch J B, Gu Y Z, Jain S, et al. The basic-helix-loophelix-pas orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc Natl Acad Sci USA, 1998, 95(10): 5474~5479 [18] Bunger M K, Wilsbacher L D, Moran S M, et al. Mop3 is an essential component of the master circadian pacemaker in mammals. Cell, 2000, 103:1009~1017 [19] Ralph M R, Menaker M. A mutation of the circadian system in golden hamsters. Science, 1998, 241: 1225~1227 [20] Lowrey P L, Shimomura K, Antoch M P, et al. Positional syntenic cloning and functional characterization of the mammalian circadian mutation tau. Science, 2000, 288: 483~492 [21] Kloss B, Price J L, Saez L, et al. The Drosophila clock gene double-time encodes a protein closely related to human casein kinase 1ε. Cell, 1998, 94: 97~107 [22] Reick M, Garcia J A, Dudley C, et al. NPAS2: an analog of clock operative in the mammalian forebrain. Science, 2001, 293: 506~509 [23] Edery I. Circadian rhythms in a nutshell. Physiol Genomics, 2000, 3: 59~74 [24] Rutter J, Reick M, McKnight S L. Metabolism and the control of circadian rhythms. Annu Rev Biochem, 2002, 71: 307~331 [25] Daan S, Albrecht U, van der Horst G T J, et al. Assembling a clock for all seasons: are there M and E oscillators in the genes? J Biol Rhythms, 2001, 16: 105~116 [26] Albrecht U. Invited review: regulation of mammalian circadian clock genes. J Appl Physiol, 2002, 92(3): 1348~1355 [27] Ginty D D, Kornhauser J M, Thompson M A, et al. Regulation of CREB phosphorylation in the suprachiasmatic nucleus by light and a circadian clock. Science, 1993, 260 (5105): 238~241 [28] Yamazaki S, Numano R, Abe M, et al. Resetting central and peripheral circadian oscillators in transgenic rats. Science, 2000, 288(5466): 682~685 [29] Balsalobre A, Brown S A, Marcacci L, et al. Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science, 2000, 289(5488): 2344~2347 [30] McNamara P, Seo S P, Rudic R D, et al. Regulation of and MOP4 by nuclear hormone receptors in the vasculature: a humoral mechanism to reset a peripheral clock. Cell, 2001, 105(7): 877~889 [31] Balsalobre A, Damiola F, Schibler U. A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell, 1998, 93(6): 929~937 [32] Stokkan K. A, Yamazaki S, Tei H, et al. Entrainment of the circadian clock in the liver by feeding. Science,2001, 291 (5503): 490~493 [33] Panda S, Antoch M P, Miller B H, et al. Coordinated transcription of key pathways in the mouse by the circadian clock. Cell, 2002, 109(3): 307~320 [34] Delaunay F, Laudet V. Circadian clock and microarrays: mammalian genome gets rhythm. Trends Genet, 2002, 18 (12): 595~597 [35] Jones C R, Campbell S S, Zone S E, et al. Familial advanced sleep-phase syndrome: a short-period circadian rhythm variant in humans. Nat Med, 1999, 5: 1062~1065 [36] Toh K L, Jones C R, He Y, et al. An h2 phosphorylation site mutation in familial advanced sleep phase syndrome. Science, 2001, 291: 1040~1043 [37] Iwase T, Kajimura N, Uchiyama M, et al. Mutation screening of the human Clock gene in circadian rhythm sleep disorders. Psychiatry Res, 2002, 109: 121~128