Gene Symbol: per2
Description: period circadian clock 2
Alias: fj43b09, wu:fj43b09, period circadian protein homolog 2, per2a, zper2
Species: zebrafish

Top Publications

  1. Hirayama J, Cardone L, Doi M, Sassone Corsi P. Common pathways in circadian and cell cycle clocks: light-dependent activation of Fos/AP-1 in zebrafish controls CRY-1a and WEE-1. Proc Natl Acad Sci U S A. 2005;102:10194-9 pubmed
    ..These findings provide strong evidence that circadian and cell cycle clocks share unique light-responsive pathways in zebrafish. ..
  2. Delaunay F, Thisse C, Thisse B, Laudet V. Differential regulation of Period 2 and Period 3 expression during development of the zebrafish circadian clock. Gene Expr Patterns. 2003;3:319-24 pubmed
    ..Here, we report the isolation of zebrafish Per2 and show the presence of a Per2 maternal mRNA in early embryos as for Per3...
  3. Hirayama J, Miyamura N, Uchida Y, Asaoka Y, Honda R, Sawanobori K, et al. Common light signaling pathways controlling DNA repair and circadian clock entrainment in zebrafish. Cell Cycle. 2009;8:2794-801 pubmed
  4. Pando M, Pinchak A, Cermakian N, Sassone Corsi P. A cell-based system that recapitulates the dynamic light-dependent regulation of the vertebrate clock. Proc Natl Acad Sci U S A. 2001;98:10178-83 pubmed
    ..In particular, activation of Per2 expression is shown to be strictly regulated and dependent on light...
  5. Hirayama J, Fukuda I, Ishikawa T, Kobayashi Y, Todo T. New role of zCRY and zPER2 as regulators of sub-cellular distributions of zCLOCK and zBMAL proteins. Nucleic Acids Res. 2003;31:935-43 pubmed
    ..We cloned zPer2 cDNA and showed that the protein product encoded by the cDNA acts as a moderate transcriptional repressor...
  6. Tamai T, Vardhanabhuti V, Foulkes N, Whitmore D. Early embryonic light detection improves survival. Curr Biol. 2004;14:R104-5 pubmed
  7. Ziv L, Gothilf Y. Period2 expression pattern and its role in the development of the pineal circadian clock in zebrafish. Chronobiol Int. 2006;23:101-12 pubmed
    ..Here we describe the role of light and of the clock gene, period2 (zper2) in the development of this rhythm...
  8. Wang H. Comparative analysis of period genes in teleost fish genomes. J Mol Evol. 2008;67:29-40 pubmed publisher
    ..two per1 genes, per1a and per1b, one per2, and one per3; medaka, fugu, and tetraodon each have two per2 genes, per2a and per2b, one per1, and one per3; sticklebacks also have per2a, per2b, and one per1 but lack per3; and per1a/..
  9. Ziv L, Gothilf Y. Circadian time-keeping during early stages of development. Proc Natl Acad Sci U S A. 2006;103:4146-51 pubmed
    ..The 24-h rhythm is then maintained throughout rapid proliferation and, remarkably, differentiation...

More Information


  1. Tamai T, Young L, Whitmore D. Light signaling to the zebrafish circadian clock by Cryptochrome 1a. Proc Natl Acad Sci U S A. 2007;104:14712-7 pubmed
  2. Hirayama J, Cho S, Sassone Corsi P. Circadian control by the reduction/oxidation pathway: catalase represses light-dependent clock gene expression in the zebrafish. Proc Natl Acad Sci U S A. 2007;104:15747-52 pubmed
    ..Treatment of light-responsive Z3 cells with H(2)O(2) triggers the induction of zCry1a and zPer2 genes and the subsequent circadian oscillation of zPer1...
  3. Weger M, Weger B, Diotel N, Rastegar S, Hirota T, Kay S, et al. Real-time in vivo monitoring of circadian E-box enhancer activity: a robust and sensitive zebrafish reporter line for developmental, chemical and neural biology of the circadian clock. Dev Biol. 2013;380:259-73 pubmed publisher
    ..Finally, it allows mapping of clock activity in the brain of a vertebrate model organism with prominent adult neurogenesis and high regeneration capacity. ..
  4. Weger B, Sahinbas M, Otto G, Mracek P, Armant O, Dolle D, et al. The light responsive transcriptome of the zebrafish: function and regulation. PLoS ONE. 2011;6:e17080 pubmed publisher
    ..These findings suggest that the mechanisms involved in period2 regulation might represent a more general pathway leading to light induced gene expression. ..
  5. Dekens M, Whitmore D. Autonomous onset of the circadian clock in the zebrafish embryo. EMBO J. 2008;27:2757-65 pubmed publisher
    ..This embryonic clock is differentially regulated from that in the adult, the transition coinciding with the appearance of several clock output processes. ..
  6. Mracek P, Santoriello C, Idda M, Pagano C, Ben Moshe Z, Gothilf Y, et al. Regulation of per and cry genes reveals a central role for the D-box enhancer in light-dependent gene expression. PLoS ONE. 2012;7:e51278 pubmed publisher
    ..We have previously identified D- and E-box elements within the promoter of the zebrafish per2 gene that together direct light-induced gene expression...
  7. Cavallari N, Frigato E, Vallone D, Fröhlich N, López Olmeda J, Foá A, et al. A blind circadian clock in cavefish reveals that opsins mediate peripheral clock photoreception. PLoS Biol. 2011;9:e1001142 pubmed publisher
    ..This comparative study pinpoints the two extra-retinal photoreceptors Melanopsin (Opn4m2) and TMT-opsin as essential upstream elements of the peripheral clock light input pathway. ..
  8. Toyama R, Chen X, Jhawar N, Aamar E, Epstein J, Reany N, et al. Transcriptome analysis of the zebrafish pineal gland. Dev Dyn. 2009;238:1813-26 pubmed publisher
    ..Among the multiple candidate genes suggested by these data, we note the identification of a tissue-specific form of the unc119 gene with a possible role in pineal development. ..
  9. Ziv L, Levkovitz S, Toyama R, Falcon J, Gothilf Y. Functional development of the zebrafish pineal gland: light-induced expression of period2 is required for onset of the circadian clock. J Neuroendocrinol. 2005;17:314-20 pubmed
    ..In the present study, we investigated the role of light and of a clock gene, zperiod2 (zper2), in the development of this rhythm...
  10. Vatine G, Vallone D, Appelbaum L, Mracek P, Ben Moshe Z, Lahiri K, et al. Light directs zebrafish period2 expression via conserved D and E boxes. PLoS Biol. 2009;7:e1000223 pubmed publisher
    ..To elucidate this key mechanism, here we focus on how light regulates transcription of the zebrafish period2 (per2) gene...
  11. Gavriouchkina D, Fischer S, Ivacevic T, Stolte J, Benes V, Dekens M. Thyrotroph embryonic factor regulates light-induced transcription of repair genes in zebrafish embryonic cells. PLoS ONE. 2010;5:e12542 pubmed publisher
    ..These data leads us to propose their involvement in light-induced UV tolerance in the zebrafish embryo. ..
  12. Lahiri K, Vallone D, Gondi S, Santoriello C, Dickmeis T, Foulkes N. Temperature regulates transcription in the zebrafish circadian clock. PLoS Biol. 2005;3:e351 pubmed
    ..Together, our results imply that several key transcriptional regulatory elements at the core of the zebrafish clock respond to temperature. ..
  13. Long Y, Li L, Li Q, He X, Cui Z. Transcriptomic characterization of temperature stress responses in larval zebrafish. PLoS ONE. 2012;7:e37209 pubmed publisher
    ..Thus, these findings provide new interesting clues for elucidation of mechanisms underlying the temperature acclimation in fish. ..
  14. Cermakian N, Pando M, Thompson C, Pinchak A, Selby C, Gutierrez L, et al. Light induction of a vertebrate clock gene involves signaling through blue-light receptors and MAP kinases. Curr Biol. 2002;12:844-8 pubmed
    ..Here, we used the light-responsive zebrafish cell line Z3 to dissect the response of the clock gene zPer2 to light...
  15. Ramos B, Moraes M, Poletini M, Lima L, Castrucci A. From blue light to clock genes in zebrafish ZEM-2S cells. PLoS ONE. 2014;9:e106252 pubmed publisher
    ..consistent with melanopsin maximal absorption, and evaluated the time course expression of per1b, cry1b, per2 and cry1a...
  16. Huang L, Zuo Z, Zhang Y, Wu M, Lin J, Wang C. Use of toxicogenomics to predict the potential toxic effect of Benzo(a)pyrene on zebrafish embryos: ocular developmental toxicity. Chemosphere. 2014;108:55-61 pubmed publisher
    ..Our results were helpful for an understanding of the toxicity of BaP. This study also indicated that microarray analysis was effective for predicting the potential toxicity of chemicals with high sensitivity and accuracy. ..
  17. Ben Moshe Z, Alon S, Mracek P, Faigenbloom L, Tovin A, Vatine G, et al. The light-induced transcriptome of the zebrafish pineal gland reveals complex regulation of the circadian clockwork by light. Nucleic Acids Res. 2014;42:3750-67 pubmed publisher
    ..Moreover, we show that dec1, as well as the core clock gene per2, is essential for light-entrainment of rhythmic locomotor activity in zebrafish larvae...
  18. Miyamura N, Hirayama J, Sawanobori K, Tamaru T, Asaoka Y, Honda R, et al. CLOCK:BMAL-independent circadian oscillation of zebrafish Cryptochrome1a gene. Biol Pharm Bull. 2009;32:1183-7 pubmed
  19. Cruz B, Brongar L, Popiolek P, Gonçalvez B, Figueiredo M, Amaral I, et al. Clock genes expression and locomotor activity are altered along the light-dark cycle in transgenic zebrafish overexpressing growth hormone. Transgenic Res. 2017;26:739-752 pubmed publisher
  20. Khan Z, Yumnamcha T, Rajiv C, Sanjita Devi H, Mondal G, Devi S, et al. Melatonin biosynthesizing enzyme genes and clock genes in ovary and whole brain of zebrafish (Danio rerio): Differential expression and a possible interplay. Gen Comp Endocrinol. 2016;233:16-31 pubmed publisher
    ..biosynthesizing enzyme genes (Tph1a, Aanat1, Aanat2 and Hiomt) and clock associated genes (Bmal1a, Clock1a, Per1b, Per2 and Cry2a) in the ovary with a comparison to whole brain in normal (LD=12h L:12h D) and altered photic conditions (..
  21. Wang Q, Tan X, Jiao S, You F, Zhang P. Analyzing cold tolerance mechanism in transgenic zebrafish (Danio rerio). PLoS ONE. 2014;9:e102492 pubmed publisher
    ..These results are clues to understanding the mechanisms underlying temperature acclimation in fish. ..
  22. Jones B, Ohno C, Allenby G, Boffa M, Levin A, Grippo J, et al. New retinoid X receptor subtypes in zebra fish (Danio rerio) differentially modulate transcription and do not bind 9-cis retinoic acid. Mol Cell Biol. 1995;15:5226-34 pubmed
    ..The discovery of these two novel receptors in zebra fish expands the functional repertoire of RXRs to include ligand-independent and dominant negative modulation of type II receptor function. ..
  23. Jerônimo R, Moraes M, de Assis L, Ramos B, Rocha T, Castrucci A. Thermal stress in Danio rerio: a link between temperature, light, thermo-TRP channels, and clock genes. J Therm Biol. 2017;68:128-138 pubmed publisher
    ..When cells were kept in LD, the expression of per1, per2, cry1a, and cry1b increased in response to heat shock, indicating that heat shock only affects clock core of LD-..
  24. Lu X, Xiang Y, Yang G, Zhang L, Wang H, Zhong S. Transcriptomic characterization of zebrafish larvae in response to mercury exposure. Comp Biochem Physiol C Toxicol Pharmacol. 2017;192:40-49 pubmed publisher
    ..Thus, these findings provide useful insights to help further understand the transcriptional response and detoxification ability of zebrafish larvae following acute exposure to mercury. ..
  25. Amaral I, Johnston I. Circadian expression of clock and putative clock-controlled genes in skeletal muscle of the zebrafish. Am J Physiol Regul Integr Comp Physiol. 2012;302:R193-206 pubmed publisher
    ..Expression of the transcriptional repressors cry1a, per1a/1b, per2, per3, nr1d2a/2b, and nr1d1 also followed a circadian pattern with peak expression at ZT0-02...
  26. Mracek P, Pagano C, Fröhlich N, Idda M, Cuesta I, López Olmeda J, et al. ERK Signaling Regulates Light-Induced Gene Expression via D-Box Enhancers in a Differential, Wavelength-Dependent Manner. PLoS ONE. 2013;8:e67858 pubmed publisher
    ..Thus, we reveal that D-box-driven gene expression is regulated via ERK/MAPK signaling in a strongly wavelength-dependent manner. ..
  27. Xiao B, Cui L, Ding C, Wang H. Effects of Lithium and 2,4-Dichlorophenol on Zebrafish: Circadian Rhythm Disorder and Molecular Effects. Zebrafish. 2017;14:209-215 pubmed publisher
    ..The mRNA levels of circadian clock-related genes, including clock1a, bmal1b, per2, and per1b, were determined...
  28. Zhao Y, Zhang K, Fent K. Regulation of zebrafish (Danio rerio) locomotor behavior and circadian rhythm network by environmental steroid hormones. Environ Pollut. 2018;232:422-429 pubmed publisher
    ..Our results suggest that steroid hormones can modulate the circadian molecular network in zebrafish and provide novel insights into their mode of actions and potential environmental risks. ..
  29. Li Z, Long Y, Zhong L, Song G, Zhang X, Yuan L, et al. RNA sequencing provides insights into the toxicogenomic response of ZF4 cells to methyl methanesulfonate. J Appl Toxicol. 2016;36:94-104 pubmed publisher
    ..These results provide insight into the genome-wide response of ZF4 cells following exposure to MMS, and this knowledge will inform future toxicogenomic data analysis and environmental health risk assessment. ..
  30. Moore H, Whitmore D. Circadian rhythmicity and light sensitivity of the zebrafish brain. PLoS ONE. 2014;9:e86176 pubmed publisher
    ..neural expression of several rhythmic and light responsive clock genes, including per3, cryptochrome1a (cry1a) and per2. Adult brain nuclei showing significant clock gene expression include the teleost equivalent of the SCN, as well as ..
  31. Peyric E, Moore H, Whitmore D. Circadian clock regulation of the cell cycle in the zebrafish intestine. PLoS ONE. 2013;8:e73209 pubmed publisher
    ..Together these results suggest that the intestinal clock integrates multiple rhythmic cues, including light and food, to function optimally. ..
  32. Long Y, Song G, Yan J, He X, Li Q, Cui Z. Transcriptomic characterization of cold acclimation in larval zebrafish. BMC Genomics. 2013;14:612 pubmed publisher
    ..These findings indicate that zebrafish larvae possess the ability to build cold-tolerance under mild low temperature and transcriptional and post-transcriptional regulations are extensively involved in this acclimation process. ..
  33. Li Y, Li G, Wang H, Du J, Yan J. Analysis of a gene regulatory cascade mediating circadian rhythm in zebrafish. PLoS Comput Biol. 2013;9:e1002940 pubmed publisher
    ..Our study describes a systematic method to discover previously unidentified TFs involved in circadian physiology in complex organisms. ..
  34. Wang M, Zhong Z, Zhong Y, Zhang W, Wang H. The zebrafish period2 protein positively regulates the circadian clock through mediation of retinoic acid receptor (RAR)-related orphan receptor α (Rorα). J Biol Chem. 2015;290:4367-82 pubmed publisher
    We report the characterization of a null mutant for zebrafish circadian clock gene period2 (per2) generated by transcription activator-like effector nuclease and a positive role of PER2 in vertebrate circadian regulation...
  35. Huang J, Zhong Z, Wang M, Chen X, Tan Y, Zhang S, et al. Circadian modulation of dopamine levels and dopaminergic neuron development contributes to attention deficiency and hyperactive behavior. J Neurosci. 2015;35:2572-87 pubmed publisher
    ..The circadian model for attention deficiency and hyperactive behavior sheds light on ADHD pathogenesis and opens avenues for exploring novel targets for diagnosis and therapy for this common psychiatric disorder. ..
  36. Du L, Darroch H, Keerthisinghe P, Ashimbayeva E, Astin J, Crosier K, et al. The innate immune cell response to bacterial infection in larval zebrafish is light-regulated. Sci Rep. 2017;7:12657 pubmed publisher
  37. Carr A, Tamai T, Young L, Ferrer V, Dekens M, Whitmore D. Light reaches the very heart of the zebrafish clock. Chronobiol Int. 2006;23:91-100 pubmed
    ..Furthermore, studies examining the process of entrainment to light pulses within this cell population are described in this review, as are experiments examining light-responsiveness of early-stage zebrafish embryos. ..
  38. Di Rosa V, Frigato E, López Olmeda J, Sánchez Vázquez F, Bertolucci C. The Light Wavelength Affects the Ontogeny of Clock Gene Expression and Activity Rhythms in Zebrafish Larvae. PLoS ONE. 2015;10:e0132235 pubmed publisher
    ..of light of different wavelengths (white, blue and red) on the onset of locomotor activity and clock gene (per1b, per2, clock1, bmal1 and dbp) expression rhythms...
  39. Idda M, Kage E, López Olmeda J, Mracek P, Foulkes N, Vallone D. Circadian timing of injury-induced cell proliferation in zebrafish. PLoS ONE. 2012;7:e34203 pubmed publisher
    ..Thus, our results point to a preferential role for the circadian clock in the timing of epidermal cell proliferation in response to injury. ..
  40. Toloza Villalobos J, Arroyo J, Opazo J. The circadian clock of teleost fish: a comparative analysis reveals distinct fates for duplicated genes. J Mol Evol. 2015;80:57-64 pubmed publisher
    ..From a functional perspective, the subfunctionalization of two ohnolog genes (PER1a and PER1b) in zebrafish highlights the power of whole-genome duplications to generate biological diversity. ..
  41. Kopp R, Billecke N, Legradi J, den Broeder M, Parekh S, Legler J. Bringing obesity to light: Rev-erbα, a central player in light-induced adipogenesis in the zebrafish?. Int J Obes (Lond). 2016;40:824-32 pubmed publisher
    ..As the pparβδ promoter includes three Rev-erbα binding sites, we hypothesize that pparβδ may be a direct target that ultimately activates Pparγ. ..
  42. Ren D, Ji C, Wang X, Wang H, Hu B. Endogenous melatonin promotes rhythmic recruitment of neutrophils toward an injury in zebrafish. Sci Rep. 2017;7:4696 pubmed publisher
    ..Together, our findings provide evidence that endogenous melatonin promotes rhythmic migration of neutrophils through cytokines in zebrafish. ..
  43. Kopp R, Schwerte T, Egg M, Sandbichler A, Egger B, Pelster B. Chronic reduction in cardiac output induces hypoxic signaling in larval zebrafish even at a time when convective oxygen transport is not required. Physiol Genomics. 2010;42A:8-23 pubmed publisher
    ..The results showed that a chronic reduction in blood flow generated hypoxic molecular signals despite partial compensation by increased oxygen carrying capacity and transiently slowed the overall development of zebrafish bre larvae. ..
  44. Wu M, Liu S, Hu L, Qu H, Pan C, Lei P, et al. Global transcriptomic analysis of zebrafish in response to embryonic exposure to three antidepressants, amitriptyline, fluoxetine and mianserin. Aquat Toxicol. 2017;192:274-283 pubmed publisher
    ..e. those encoding nuclear receptor subfamily 1, group D, member 1 (nr1d1) and period 2 (per2); and genes encoding early growth response factors (egr1 and egr4), in the antidepressant-treated fish larvae...
  45. Jensen L, Cao Z, Nakamura M, Yang Y, Bräutigam L, Andersson P, et al. Opposing effects of circadian clock genes bmal1 and period2 in regulation of VEGF-dependent angiogenesis in developing zebrafish. Cell Rep. 2012;2:231-41 pubmed publisher
    ..These results shed mechanistic insight on the role of the circadian clock in regulation of developmental angiogenesis, and our findings may be reasonably extended to other types of physiological or pathological angiogenesis. ..
  46. Xiao B, Chen T, Zhong Y. Possible molecular mechanism underlying cadmium-induced circadian rhythms disruption in zebrafish. Biochem Biophys Res Commun. 2016;481:201-205 pubmed publisher
    ..The mRNA levels of clock1a, bmal1b, per2 and per1b in two groups were determined. Microarray data were generated in two group of samples...
  47. Purushothaman S, Saxena S, Meghah V, Meena Lakshmi M, Singh S, Brahmendra Swamy C, et al. Proteomic and gene expression analysis of zebrafish brain undergoing continuous light/dark stress. J Sleep Res. 2015;24:458-65 pubmed publisher
    ..It is hypothesized that the differential regulation of these genes might lead to the discovery of potential diagnostic markers for gaining insight into the light/dark-associated stress in humans. ..
  48. Osaki T, Uchida Y, Hirayama J, Nishina H. Diphenyleneiodonium chloride, an inhibitor of reduced nicotinamide adenine dinucleotide phosphate oxidase, suppresses light-dependent induction of clock and DNA repair genes in zebrafish. Biol Pharm Bull. 2011;34:1343-7 pubmed
    ..Our findings also support the existence of a regulatory link between photoreactivation and the circadian clock in this species. ..
  49. Pelster B, Egg M. Multiplicity of hypoxia-inducible transcription factors and their connection to the circadian clock in the zebrafish. Physiol Biochem Zool. 2015;88:146-57 pubmed publisher