Gene Symbol: Per2
Description: period circadian clock 2
Alias: mKIAA0347, mPer2, period circadian protein homolog 2, circadian clock protein PERIOD 2, period 2, period homolog 2
Species: mouse
Products:     Per2

Top Publications

  1. Aton S, Huettner J, Straume M, Herzog E. GABA and Gi/o differentially control circadian rhythms and synchrony in clock neurons. Proc Natl Acad Sci U S A. 2006;103:19188-93 pubmed
    ..We propose that G(i/o), not GABA activity, converges with VIP signaling to maintain and coordinate rhythms among SCN neurons. ..
  2. Jin X, Shearman L, Weaver D, Zylka M, de Vries G, Reppert S. A molecular mechanism regulating rhythmic output from the suprachiasmatic circadian clock. Cell. 1999;96:57-68 pubmed
    ..These data indicate that the transcriptional machinery of the core clockwork directly regulates a clock-controlled output rhythm. ..
  3. Zhao W, Malinin N, Yang F, Staknis D, Gekakis N, Maier B, et al. CIPC is a mammalian circadian clock protein without invertebrate homologues. Nat Cell Biol. 2007;9:268-75 pubmed
    ..Our results suggest that negative feedback in the mammalian circadian clock is divided into distinct pathways, and that the addition of new genes has contributed to the complexity of vertebrate clocks. ..
  4. Moriya T, Hiraishi K, Horie N, Mitome M, Shinohara K. Correlative association between circadian expression of mousePer2 gene and the proliferation of the neural stem cells. Neuroscience. 2007;146:494-8 pubmed
    We examined the circadian expression of mousePeriod (mPer) genes (mPer1 and mPer2) and the proliferation of the neural stem cells in vitro...
  5. Fu L, Pelicano H, Liu J, Huang P, Lee C. The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell. 2002;111:41-50 pubmed
    ..The Period2 gene plays a key role in controlling circadian rhythm in mice. We report here that mice deficient in the mPer2 gene are cancer prone...
  6. Eide E, Woolf M, Kang H, Woolf P, Hurst W, Camacho F, et al. Control of mammalian circadian rhythm by CKIepsilon-regulated proteasome-mediated PER2 degradation. Mol Cell Biol. 2005;25:2795-807 pubmed
    ..We have developed a cell-based model of PER2 degradation. Murine PER2 (mPER2) hyperphosphorylation induced by the cell-permeable protein phosphatase inhibitor calyculin A is rapidly followed ..
  7. Hua H, Wang Y, Wan C, Liu Y, Zhu B, Yang C, et al. Circadian gene mPer2 overexpression induces cancer cell apoptosis. Cancer Sci. 2006;97:589-96 pubmed
    ..We examined whether overexpression of the mouse Period2 gene (mPer2) in tumor cells influences cell growth and induces apoptosis...
  8. Duong H, Weitz C. Temporal orchestration of repressive chromatin modifiers by circadian clock Period complexes. Nat Struct Mol Biol. 2014;21:126-32 pubmed publisher
    ..PER proteins recruited HP1?-Suv39h to the Per1 and Per2 promoters, and HP1?-Suv39h proved important for circadian di- and trimethylation of histone H3 Lys9 (H3K9) at the ..
  9. Pendergast J, Yamazaki S. Masking responses to light in period mutant mice. Chronobiol Int. 2011;28:657-63 pubmed publisher
    ..The circadian genes, Period1 (Per1) and Per2, are necessary components of the timekeeping machinery and entrainment by light appears to involve the induction of ..

More Information

Publications101 found, 100 shown here

  1. Zylka M, Shearman L, Levine J, Jin X, Weaver D, Reppert S. Molecular analysis of mammalian timeless. Neuron. 1998;21:1115-22 pubmed
    ..The data suggest that PER-PER interactions have replaced the function of PER-TIM dimers in the molecular workings of the mammalian circadian clock. ..
  2. Godinho S, Maywood E, Shaw L, Tucci V, Barnard A, Busino L, et al. The after-hours mutant reveals a role for Fbxl3 in determining mammalian circadian period. Science. 2007;316:897-900 pubmed
    ..The Afh allele significantly affected Per2 expression and delayed the rate of Cry protein degradation in Per2::Luciferase tissue slices...
  3. Foley N, Tong T, Foley D, LeSauter J, Welsh D, Silver R. Characterization of orderly spatiotemporal patterns of clock gene activation in mammalian suprachiasmatic nucleus. Eur J Neurosci. 2011;33:1851-65 pubmed publisher
    ..Using cluster analysis to assess bioluminescence in acute brain slices from PERIOD2::Luciferase (PER2::LUC) knockin mice, and immunochemistry of SCN from animals harvested at various circadian times, we assessed the ..
  4. Miki T, Xu Z, Chen Goodspeed M, Liu M, Van Oort Jansen A, Rea M, et al. PML regulates PER2 nuclear localization and circadian function. EMBO J. 2012;31:1427-39 pubmed publisher
    Studies have suggested that the clock regulator PER2 is a tumour suppressor. A cancer network involving PER2 raises the possibility that some tumour suppressors are directly involved in the mammalian clock...
  5. Travnickova Bendova Z, Cermakian N, Reppert S, Sassone Corsi P. Bimodal regulation of mPeriod promoters by CREB-dependent signaling and CLOCK/BMAL1 activity. Proc Natl Acad Sci U S A. 2002;99:7728-33 pubmed
    ..Three Per genes exist in the mouse. Whereas mPer1 and mPer2 are light-inducible in clock neurons of the hypothalamic suprachiasmatic nucleus, mPer3 is not...
  6. Curtis A, Seo S, Westgate E, Rudic R, Smyth E, Chakravarti D, et al. Histone acetyltransferase-dependent chromatin remodeling and the vascular clock. J Biol Chem. 2004;279:7091-7 pubmed
    ..Temporal coactivator recruitment and HAT-dependent chromatin remodeling on the promoter of clock controlled genes in the vasculature permits the mammalian clock to orchestrate circadian gene expression. ..
  7. Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, et al. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell. 2008;134:317-28 pubmed publisher required for high-magnitude circadian transcription of several core clock genes, including Bmal1, Rorgamma, Per2, and Cry1. SIRT1 binds CLOCK-BMAL1 in a circadian manner and promotes the deacetylation and degradation of PER2...
  8. Padmanabhan K, Robles M, Westerling T, Weitz C. Feedback regulation of transcriptional termination by the mammalian circadian clock PERIOD complex. Science. 2012;337:599-602 pubmed publisher
    ..Circadian clock negative feedback thus includes direct control of transcriptional termination. ..
  9. Yoshimura T, Suzuki Y, Makino E, Suzuki T, Kuroiwa A, Matsuda Y, et al. Molecular analysis of avian circadian clock genes. Brain Res Mol Brain Res. 2000;78:207-15 pubmed
    ..qPER2 and qPER3 showed approximately 79%, approximately 46% and approximately 33% amino acid identity to mCLOCK, mPER2, mPER3, respectively. Clock was mapped to quail chromosome 4 and chicken chromosome 4q1.6-q2.1...
  10. Kiyohara Y, Tagao S, Tamanini F, Morita A, Sugisawa Y, Yasuda M, et al. The BMAL1 C terminus regulates the circadian transcription feedback loop. Proc Natl Acad Sci U S A. 2006;103:10074-9 pubmed
    ..C-terminally truncated BMAL1 mutant proteins still associate with mPER2 (another protein of the negative feedback loop), suggesting that an additional repression mechanism may converge ..
  11. Bae K, Lee K, Seo Y, Lee H, Kim D, Choi I. Differential effects of two period genes on the physiology and proteomic profiles of mouse anterior tibialis muscles. Mol Cells. 2006;22:275-84 pubmed
    ..Examination of mice with targeted disruptions of either mPer1 or mPer2 has shown that these two genes have key roles in the SCN circadian clock...
  12. Liu A, Welsh D, Ko C, Tran H, Zhang E, Priest A, et al. Intercellular coupling confers robustness against mutations in the SCN circadian clock network. Cell. 2007;129:605-16 pubmed
    ..Here, we used bioluminescence imaging to monitor Per2 gene expression in tissues and cells from clock mutant mice...
  13. Wood P, Yang X, Taber A, Oh E, Ansell C, Ayers S, et al. Period 2 mutation accelerates ApcMin/+ tumorigenesis. Mol Cancer Res. 2008;6:1786-93 pubmed publisher
    ..Intestinal epithelial cell proliferation is gated throughout each day by the circadian clock. Period 2 (Per2) is a key circadian clock gene...
  14. Sosniyenko S, Hut R, Daan S, Sumova A. Influence of photoperiod duration and light-dark transitions on entrainment of Per1 and Per2 gene and protein expression in subdivisions of the mouse suprachiasmatic nucleus. Eur J Neurosci. 2009;30:1802-14 pubmed publisher
    ..with twilight relative to that with rectangular light-to-dark transition on the daily profiles of Per1 and Per2 mRNA (in situ hybridization) and PER1 and PER2 protein (immunohistochemistry) levels within the rostral, middle and ..
  15. Tamaru T, Hattori M, Honda K, Benjamin I, Ozawa T, Takamatsu K. Synchronization of circadian Per2 rhythms and HSF1-BMAL1:CLOCK interaction in mouse fibroblasts after short-term heat shock pulse. PLoS ONE. 2011;6:e24521 pubmed publisher
    ..Circadian Per2 rhythm and HSF1-mediated gene expression were monitored by a real-time bioluminescence assay for mPer2 promoter-driven luciferase and HS element (HSE; HSF1-binding site)-driven luciferase activity, respectively...
  16. Pilorz V, Steinlechner S. Low reproductive success in Per1 and Per2 mutant mouse females due to accelerated ageing?. Reproduction. 2008;135:559-68 pubmed publisher
    ..In order to determine whether two other molecular components of the main clock, namely the period genes, Per1 and Per2, have an effect on the length of the oestrous cycle and the reproductive success, we used Per1- and Per2-deficient ..
  17. Lee H, Chen R, Lee Y, Yoo S, Lee C. Essential roles of CKIdelta and CKIepsilon in the mammalian circadian clock. Proc Natl Acad Sci U S A. 2009;106:21359-64 pubmed publisher
    ..CKIdelta/epsilon while avoiding the embryonic lethality of CKIdelta disruption in mice, we used CKIdelta-deficient Per2(Luc) mouse embryonic fibroblasts (MEFs) and overexpressed a dominant-negative mutant CKIepsilon (DN-CKIepsilon) in ..
  18. Vukolic A, Antic V, Van Vliet B, Yang Z, Albrecht U, Montani J. Role of mutation of the circadian clock gene Per2 in cardiovascular circadian rhythms. Am J Physiol Regul Integr Comp Physiol. 2010;298:R627-34 pubmed publisher
    ..Our data show that mutation of the Period2 gene results in an attenuated dipping of blood pressure and heart rate during both light-dark cycles and constant darkness, and in shorter circadian periods during constant darkness. ..
  19. Virag J, Dries J, Easton P, Friesland A, DeAntonio J, Chintalgattu V, et al. Attenuation of myocardial injury in mice with functional deletion of the circadian rhythm gene mPer2. Am J Physiol Heart Circ Physiol. 2010;298:H1088-95 pubmed publisher
    ..Thus we sought to determine whether the functional deletion of the circadian rhythm mouse periodic gene 2 (mPer2) would protect the heart against ischemic injury...
  20. Cheng M, Bullock C, Li C, Lee A, Bermak J, Belluzzi J, et al. Prokineticin 2 transmits the behavioural circadian rhythm of the suprachiasmatic nucleus. Nature. 2002;417:405-10 pubmed
    ..The high expression of PKR2 mRNA within the SCN and the positive feedback of PK2 on its own transcription through activation of PKR2 suggest that PK2 may also function locally within the SCN to synchronize output. ..
  21. Yoo S, Yamazaki S, Lowrey P, Shimomura K, Ko C, Buhr E, et al. PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. Proc Natl Acad Sci U S A. 2004;101:5339-46 pubmed
    ..Surprisingly, lesions of the SCN in mPer2(Luciferase) knockin mice did not abolish circadian rhythms in peripheral tissues, but instead caused phase ..
  22. Xu Y, Toh K, Jones C, Shin J, Fu Y, Ptacek L. Modeling of a human circadian mutation yields insights into clock regulation by PER2. Cell. 2007;128:59-70 pubmed
    ..A mutation in human Period 2 (hPER2), a gene crucial for resetting the central clock in response to light, is associated with familial ..
  23. Lamia K, Storch K, Weitz C. Physiological significance of a peripheral tissue circadian clock. Proc Natl Acad Sci U S A. 2008;105:15172-7 pubmed publisher
    ..Our findings suggest that the liver clock contributes to homeostasis by driving a daily rhythm of hepatic glucose export that counterbalances the daily cycle of glucose ingestion resulting from the fasting-feeding cycle. ..
  24. Sasaki M, Yoshitane H, Du N, Okano T, Fukada Y. Preferential inhibition of BMAL2-CLOCK activity by PER2 reemphasizes its negative role and a positive role of BMAL2 in the circadian transcription. J Biol Chem. 2009;284:25149-59 pubmed publisher
    ..In contrast, PER2 showed a stronger inhibitory effect on BMAL2-CLOCK than on BMAL1-CLOCK...
  25. Pendergast J, Friday R, Yamazaki S. Distinct functions of Period2 and Period3 in the mouse circadian system revealed by in vitro analysis. PLoS ONE. 2010;5:e8552 pubmed publisher
    ..and Per1-promoter-driven luciferase expression (Per1-luc) in cultured SCN, pituitary, and lung explants from Per2(-/-) and Per3(-/-) mice congenic with the C57BL/6J strain...
  26. Wang X, Tang J, Xing L, Shi G, Ruan H, Gu X, et al. Interaction of MAGED1 with nuclear receptors affects circadian clock function. EMBO J. 2010;29:1389-400 pubmed publisher
    ..We have thus identified and defined a novel circadian regulator, Maged1, which is indispensable for the robustness of the circadian clock to better serve the organism. ..
  27. Mendez Ferrer S, Lucas D, Battista M, Frenette P. Haematopoietic stem cell release is regulated by circadian oscillations. Nature. 2008;452:442-7 pubmed publisher
    ..These data indicate that a circadian, neurally driven release of HSC during the animal's resting period may promote the regeneration of the stem cell niche and possibly other tissues. ..
  28. Mickman C, Stubblefield J, Stubblefield J, Harrington M, NELSON D. Photoperiod alters phase difference between activity onset in vivo and mPer2::luc peak in vitro. Am J Physiol Regul Integr Comp Physiol. 2008;295:R1688-94 pubmed publisher
    ..Utilizing rhythms of in vivo behavior and in vitro mPer2::luc expression, we investigated whether different entrainment photoperiods [light:dark (L:D) 16:8 and L:D 8:16] ..
  29. Ruan G, Allen G, Yamazaki S, McMahon D. An autonomous circadian clock in the inner mouse retina regulated by dopamine and GABA. PLoS Biol. 2008;6:e249 pubmed publisher
    ..allows retinal circadian rhythms to be monitored in real time as luminescence rhythms from a PERIOD2::LUCIFERASE (PER2::LUC) clock gene reporter...
  30. Lee S, Donehower L, Herron A, Moore D, Fu L. Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice. PLoS ONE. 2010;5:e10995 pubmed publisher
    ..the circadian genes Period1 and 2 (Per) or Cryptochrome1 and 2 (Cry) are deficient in cell cycle regulation and Per2 mutant mice are cancer-prone...
  31. Bedont J, Legates T, Slat E, Byerly M, Wang H, Hu J, et al. Lhx1 controls terminal differentiation and circadian function of the suprachiasmatic nucleus. Cell Rep. 2014;7:609-22 pubmed publisher
    ..These animals provide a platform for studying the central oscillator's role in physiology and cognition. ..
  32. Akashi M, Tsuchiya Y, Yoshino T, Nishida E. Control of intracellular dynamics of mammalian period proteins by casein kinase I epsilon (CKIepsilon) and CKIdelta in cultured cells. Mol Cell Biol. 2002;22:1693-703 pubmed
    ..These results suggest that CKIepsilon and CKIdelta regulate the mammalian circadian autoregulatory loop by controlling both protein turnover and subcellular localization of mPer proteins. ..
  33. Buhr E, Yoo S, Takahashi J. Temperature as a universal resetting cue for mammalian circadian oscillators. Science. 2010;330:379-85 pubmed publisher
    ..These results suggest that the evolutionarily ancient temperature resetting response can be used in homeothermic animals to enhance internal circadian synchronization. ..
  34. Anand S, Maywood E, Chesham J, Joynson G, Banks G, Hastings M, et al. Distinct and separable roles for endogenous CRY1 and CRY2 within the circadian molecular clockwork of the suprachiasmatic nucleus, as revealed by the Fbxl3(Afh) mutation. J Neurosci. 2013;33:7145-53 pubmed publisher
    ..Incorporation of CRY-mediated transcriptional feedback thus confers stability to intrinsic SCN oscillations, establishing periods between 18 and 29 h, as determined by selective contributions of CRY1 and CRY2. ..
  35. Maywood E, Drynan L, Chesham J, Edwards M, Dardente H, Fustin J, et al. Analysis of core circadian feedback loop in suprachiasmatic nucleus of mCry1-luc transgenic reporter mouse. Proc Natl Acad Sci U S A. 2013;110:9547-52 pubmed publisher
    ..The mCry1-luc mouse therefore reports circadian mCry1 expression and its interactions with vasoactive intestinal peptide, cAMP, and PER at the heart of the SCN pacemaker. ..
  36. Yan L, Silver R. Resetting the brain clock: time course and localization of mPER1 and mPER2 protein expression in suprachiasmatic nuclei during phase shifts. Eur J Neurosci. 2004;19:1105-9 pubmed
    ..In a previous study we investigated light-induced expression of mPer1 and mPer2 mRNA in the suprachiasmatic nuclei (SCN), with the aim of understanding the relationship between gene expression ..
  37. Xu Y, Padiath Q, Shapiro R, Jones C, Wu S, Saigoh N, et al. Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome. Nature. 2005;434:640-4 pubmed result from a mutation in a phosphorylation site within the casein kinase I (CKI)-binding domain of the human PER2 gene...
  38. Meng Q, Maywood E, Bechtold D, Lu W, Li J, Gibbs J, et al. Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes. Proc Natl Acad Sci U S A. 2010;107:15240-5 pubmed publisher
    ..Period lengthening mediated by CK1delta inhibition was accompanied by nuclear retention of PER2 protein both in vitro and in vivo...
  39. Dunlap J. Molecular bases for circadian clocks. Cell. 1999;96:271-90 pubmed
  40. Vielhaber E, Eide E, Rivers A, Gao Z, Virshup D. Nuclear entry of the circadian regulator mPER1 is controlled by mammalian casein kinase I epsilon. Mol Cell Biol. 2000;20:4888-99 pubmed
    ..Unlike both dPER and mPER2, mPER1 expressed alone in HEK 293 cells is predominantly a nuclear protein...
  41. Yamamoto Y, Yagita K, Okamura H. Role of cyclic mPer2 expression in the mammalian cellular clock. Mol Cell Biol. 2005;25:1912-21 pubmed
    To explore the role of mPer2 in the circadian oscillation in the mammalian cellular clock, we established fibroblast cell lines in which expression of mPer2 is controlled through a tetracycline-regulatable promoter...
  42. Ripperger J, Schibler U. Rhythmic CLOCK-BMAL1 binding to multiple E-box motifs drives circadian Dbp transcription and chromatin transitions. Nat Genet. 2006;38:369-74 pubmed
    ..The rhythmic conversion of transcriptionally permissive chromatin to facultative heterochromatin relies on the presence of functional BMAL1-CLOCK binding sites. ..
  43. Zhang J, Zhu B, Liu Y, Jiang Z, Wang Y, Li Y, et al. High expression of circadian gene mPer2 diminishes radiosensitivity of tumor cells. Cancer Biother Radiopharm. 2008;23:561-70 pubmed publisher
    ..Lewis lung carcinoma (LLC) and EMT6 cells were induced by phorbol myristate acetate or transfected with pcDNA3.1-mPer2 and irradiated with 60Co-gamma-rays, then analyzed with several methods, such as flow cytometry, single-cell gel ..
  44. Schmutz I, Ripperger J, Baeriswyl Aebischer S, Albrecht U. The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors. Genes Dev. 2010;24:345-57 pubmed publisher
    ..Here we show that the core loop component PER2 can coordinate circadian output with the circadian oscillator...
  45. Bae K, Jin X, Maywood E, Hastings M, Reppert S, Weaver D. Differential functions of mPer1, mPer2, and mPer3 in the SCN circadian clock. Neuron. 2001;30:525-36 pubmed
    The role of mPer1 and mPer2 in regulating circadian rhythms was assessed by disrupting these genes...
  46. Gery S, Gombart A, Yi W, Koeffler C, Hofmann W, Koeffler H. Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia. Blood. 2005;106:2827-36 pubmed
    ..Our microarray data showed that the expression levels of 2 core components of the circadian network, Per2 and Rev-Erbalpha, were significantly altered by C/EBPs...
  47. Feillet C, Ripperger J, Magnone M, Dulloo A, Albrecht U, Challet E. Lack of food anticipation in Per2 mutant mice. Curr Biol. 2006;16:2016-22 pubmed
    ..Period genes Per1 and Per2 are crucial for the SCN's resetting to light ...
  48. Debruyne J, Weaver D, Reppert S. CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock. Nat Neurosci. 2007;10:543-5 pubmed
    ..Here we report that the transcription factor NPAS2 (MOP4) is able to functionally substitute for CLOCK in the master brain clock in mice to regulate circadian rhythmicity. ..
  49. Koike N, Yoo S, Huang H, Kumar V, Lee C, Kim T, et al. Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science. 2012;338:349-54 pubmed publisher
    ..We also find that circadian modulation of RNAPII recruitment and chromatin remodeling occurs on a genome-wide scale far greater than that seen previously by gene expression profiling. ..
  50. Bae K, Weaver D. Light-induced phase shifts in mice lacking mPER1 or mPER2. J Biol Rhythms. 2003;18:123-33 pubmed
    Three homologs of the Drosophila Period gene have been identified in mammals. In mice, these three genes (mPer1, mPer2, and mPer3) have distinct roles in the circadian clockwork...
  51. Ohno T, Onishi Y, Ishida N. A novel E4BP4 element drives circadian expression of mPeriod2. Nucleic Acids Res. 2007;35:648-55 pubmed
    ..that the circadian E2 enhancer (a non-canonical E-box) accounts for most of the circadian transcriptional drive of mPer2, little is known about the other cis-elements of mPer2 oscillatory transcription...
  52. Langmesser S, Tallone T, Bordon A, Rusconi S, Albrecht U. Interaction of circadian clock proteins PER2 and CRY with BMAL1 and CLOCK. BMC Mol Biol. 2008;9:41 pubmed publisher
    ..the mechanism how positive and negative components of the clock interplay, we characterized the interactions of PER2, CRY1 and CRY2 with BMAL1 and CLOCK using a mammalian two-hybrid system and co-immunoprecipitation assays...
  53. Kondratov R, Chernov M, Kondratova A, Gorbacheva V, Gudkov A, Antoch M. BMAL1-dependent circadian oscillation of nuclear CLOCK: posttranslational events induced by dimerization of transcriptional activators of the mammalian clock system. Genes Dev. 2003;17:1921-32 pubmed
    ..Altogether, these results provide evidence for an additional level of circadian system control, which is based on regulation of transcriptional activity or/and availability of CLOCK/BMAL1 complex. ..
  54. Zhang J, Kaasik K, Blackburn M, Lee C. Constant darkness is a circadian metabolic signal in mammals. Nature. 2006;439:340-3 pubmed
    ..Induction of mClps expression by 5'-AMP in LD mice was reciprocally linked to blood glucose levels. Our findings uncover a circadian metabolic rhythm in mammals. ..
  55. Miyazaki K, Wakabayashi M, Hara Y, Ishida N. Tumor growth suppression in vivo by overexpression of the circadian component, PER2. Genes Cells. 2010;15:351-8 pubmed publisher
    Some reports have indicated that the core clock gene, Per2 regulates the cell cycle, immune system and neural functions...
  56. Ozber N, Baris I, Tatlici G, Gur I, Kilinc S, Unal E, et al. Identification of two amino acids in the C-terminal domain of mouse CRY2 essential for PER2 interaction. BMC Mol Biol. 2010;11:69 pubmed publisher
    ..We identified a region on mCRY2 (between residues 493 and 512) responsible for direct physical interaction with mPER2 by mammalian two-hybrid and co-immunoprecipitation assays...
  57. Noguchi T, Wang L, Welsh D. Fibroblast PER2 circadian rhythmicity depends on cell density. J Biol Rhythms. 2013;28:183-92 pubmed publisher single-cell circadian oscillators in high- and low-density culture, by single-cell imaging of cells from PER2::LUC circadian reporter mice...
  58. Welsh D, Yoo S, Liu A, Takahashi J, Kay S. Bioluminescence imaging of individual fibroblasts reveals persistent, independently phased circadian rhythms of clock gene expression. Curr Biol. 2004;14:2289-95 pubmed
    ..imaging of Rat-1 fibroblasts transfected with a Bmal1::luc plasmid and primary fibroblasts dissociated from mPer2(Luciferase-SV40) knockin mice, we monitored single-cell circadian rhythms of clock gene expression for 1-2 weeks...
  59. Liu J, Malkani G, Mankani G, Shi X, Meyer M, Cunningham Runddles S, et al. The circadian clock Period 2 gene regulates gamma interferon production of NK cells in host response to lipopolysaccharide-induced endotoxic shock. Infect Immun. 2006;74:4750-6 pubmed
    The Period 2 (Per2) gene is a key molecular component in controlling mammalian circadian rhythms at the levels of gene expression, physiology, and pathogenesis...
  60. Webb A, Angelo N, Huettner J, Herzog E. Intrinsic, nondeterministic circadian rhythm generation in identified mammalian neurons. Proc Natl Acad Sci U S A. 2009;106:16493-8 pubmed publisher
    ..Instead, these results indicate that AVP, VIP, and other SCN neurons are intrinsic but unstable circadian oscillators that rely on network interactions to stabilize their otherwise noisy cycling. ..
  61. Hirano A, Yumimoto K, Tsunematsu R, Matsumoto M, Oyama M, Kozuka Hata H, et al. FBXL21 regulates oscillation of the circadian clock through ubiquitination and stabilization of cryptochromes. Cell. 2013;152:1106-18 pubmed publisher
    ..These results emphasize the physiological importance of antagonizing actions between FBXL21 and FBXL3 on CRYs, and their combined actions at different subcellular locations stabilize oscillation of the circadian clock. ..
  62. Shearman L, Sriram S, Weaver D, Maywood E, Chaves I, Zheng B, et al. Interacting molecular loops in the mammalian circadian clock. Science. 2000;288:1013-9 pubmed
    ..PERIOD2 is a positive regulator of the Bmal1 loop, and CRYPTOCHROMES are the negative regulators of the Period and Cryptochrome cycles. ..
  63. Shimomura H, Moriya T, Sudo M, Wakamatsu H, Akiyama M, Miyake Y, et al. Differential daily expression of Per1 and Per2 mRNA in the suprachiasmatic nucleus of fetal and early postnatal mice. Eur J Neurosci. 2001;13:687-93 pubmed
    ..Daily rhythms of mRNA content were observed in mPer1 but not mPer2 in the fetal SCN...
  64. Hampp G, Ripperger J, Houben T, Schmutz I, Blex C, Perreau Lenz S, et al. Regulation of monoamine oxidase A by circadian-clock components implies clock influence on mood. Curr Biol. 2008;18:678-83 pubmed publisher
    ..transcription of the monoamine oxidase A (Maoa) promoter is regulated by the clock components BMAL1, NPAS2, and PER2. A mutation in the clock gene Per2 in mice leads to reduced expression and activity of MAOA in the mesolimbic ..
  65. An S, Harang R, Meeker K, Granados Fuentes D, Tsai C, Mazuski C, et al. A neuropeptide speeds circadian entrainment by reducing intercellular synchrony. Proc Natl Acad Sci U S A. 2013;110:E4355-61 pubmed publisher
    ..We show that exploiting these mechanisms that transiently reduce cellular synchrony before a large shift in the schedule of daily environmental cues has the potential to reduce jet lag. ..
  66. Yagita K, Yamaguchi S, Tamanini F, van der Horst G, Hoeijmakers J, Yasui A, et al. Dimerization and nuclear entry of mPER proteins in mammalian cells. Genes Dev. 2000;14:1353-63 pubmed
    ..Here we report that nuclear translocation of mPER1 and mPER2 (1) involves physical interactions with mPER3, (2) is accelerated by serum treatment, and (3) still occurs in ..
  67. Abarca C, Albrecht U, Spanagel R. Cocaine sensitization and reward are under the influence of circadian genes and rhythm. Proc Natl Acad Sci U S A. 2002;99:9026-30 pubmed
    ..Here we show that the mouse homologues of the Drosophila Per gene, mPer1 and mPer2, modulate cocaine sensitization and reward, two phenomena extensively studied in humans and animals because of ..
  68. Kopp C, Albrecht U, Zheng B, Tobler I. Homeostatic sleep regulation is preserved in mPer1 and mPer2 mutant mice. Eur J Neurosci. 2002;16:1099-106 pubmed
    A limited set of genes, Clock, Bmal1, mPer1, mPer2, mCry1 and mCry2, has been shown to be essential for the generation of circadian rhythms in mammals...
  69. Kaasik K, Lee C. Reciprocal regulation of haem biosynthesis and the circadian clock in mammals. Nature. 2004;430:467-71 pubmed
    ..Here we show that haem differentially modulates expression of the mammalian Period genes mPer1 and mPer2 in vivo by a mechanism involving NPAS2 and mPER2...
  70. Wang C, Wen M, Wang H, Hsieh I, Li Y, Liu P, et al. Increased vascular senescence and impaired endothelial progenitor cell function mediated by mutation of circadian gene Per2. Circulation. 2008;118:2166-73 pubmed publisher
    Alteration of the circadian rhythm and increased vascular senescence are linked to cardiovascular disease. Per2, a circadian gene, is known to regulate endothelium-dependent vasomotion...
  71. Ansari N, Agathagelidis M, Lee C, Korf H, Von Gall C. Differential maturation of circadian rhythms in clock gene proteins in the suprachiasmatic nucleus and the pars tuberalis during mouse ontogeny. Eur J Neurosci. 2009;29:477-89 pubmed publisher
    ..Thus, our data provide the first evidence that maternal melatonin is important for establishing and maintaining circadian rhythms in a foetal peripheral oscillator. ..
  72. Chaves I, Yagita K, Barnhoorn S, Okamura H, van der Horst G, Tamanini F. Functional evolution of the photolyase/cryptochrome protein family: importance of the C terminus of mammalian CRY1 for circadian core oscillator performance. Mol Cell Biol. 2006;26:1743-53 pubmed
    ..via two independent mechanisms and shift the equilibrium of shuttling mammalian CRY1 (mCRY1)/mammalian PER2 (mPER2) complexes towards the nucleus...
  73. Mohawk J, Baer M, Menaker M. The methamphetamine-sensitive circadian oscillator does not employ canonical clock genes. Proc Natl Acad Sci U S A. 2009;106:3519-24 pubmed publisher
    ..The properties of MASCO may provide insight into the evolution of circadian mechanisms. Importantly, MASCO may play a role in addiction to psychostimulants. ..
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    ..Our results favor a scenario in which H3K4 trimethylation by MLL1 is required to establish a permissive chromatin state for circadian transcription. ..
  75. Gu X, Xing L, Shi G, Liu Z, Wang X, Qu Z, et al. The circadian mutation PER2(S662G) is linked to cell cycle progression and tumorigenesis. Cell Death Differ. 2012;19:397-405 pubmed publisher
    ..A mutation (S662G) in the clock protein PERIOD2 (PER2) is responsible for familial advanced sleep phase syndrome in which sleep onset occurs in the early evening and ..
  76. Viswambharan H, Carvas J, Antic V, Marecic A, Jud C, Zaugg C, et al. Mutation of the circadian clock gene Per2 alters vascular endothelial function. Circulation. 2007;115:2188-95 pubmed
    ..In the present study, we investigated the role of the circadian clock gene Period2 (Per2) in endothelial function in a mouse model...
  77. Siepka S, Yoo S, Park J, Song W, Kumar V, Hu Y, et al. Circadian mutant Overtime reveals F-box protein FBXL3 regulation of cryptochrome and period gene expression. Cell. 2007;129:1011-23 pubmed
    ..In Ovtm mice, expression of the PERIOD proteins PER1 and PER2 is reduced; however, the CRY proteins CRY1 and CRY2 are unchanged...
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    ..We determined that a GRE within the core clock gene Per2 was continuously occupied during rhythmic expression and essential for glucocorticoid regulation of that gene in ..
  80. Dolatshad H, Cary A, Davis F. Differential expression of the circadian clock in maternal and embryonic tissues of mice. PLoS ONE. 2010;5:e9855 pubmed publisher
    ..Using a bioluminescent fusion protein that tracks translation of the circadian gene, per2, we also analyzed protein levels...
  81. Fu L, Patel M, Bradley A, Wagner E, Karsenty G. The molecular clock mediates leptin-regulated bone formation. Cell. 2005;122:803-15 pubmed
    ..Thus, leptin determines the extent of bone formation by modulating, via sympathetic signaling, osteoblast proliferation through two antagonistic pathways, one of which involves the molecular clock. ..
  82. Franken P, Thomason R, Heller H, O Hara B. A non-circadian role for clock-genes in sleep homeostasis: a strain comparison. BMC Neurosci. 2007;8:87 pubmed
    ..Here we follow the time course of the forebrain changes in the expression of the clock-genes period (per)-1, per2, and of the clock-controlled gene albumin D-binding protein (dbp) during a 6 h SD and subsequent recovery sleep in ..
  83. Takumi T, Matsubara C, Shigeyoshi Y, Taguchi K, Yagita K, Maebayashi Y, et al. A new mammalian period gene predominantly expressed in the suprachiasmatic nucleus. Genes Cells. 1998;3:167-76 pubmed
    ..A mammalian period complementary DNA, mPer2, has been isolated from the mouse brain...
  84. Tahara Y, Otsuka M, Fuse Y, Hirao A, Shibata S. Refeeding after fasting elicits insulin-dependent regulation of Per2 and Rev-erb? with shifts in the liver clock. J Biol Rhythms. 2011;26:230-40 pubmed publisher
    ..The expressions of liver Per2 and Rev-erb? genes were phase-advanced within 1 day of refeeding...
  85. Schmalen I, Reischl S, Wallach T, Klemz R, Grudziecki A, Prabu J, et al. Interaction of circadian clock proteins CRY1 and PER2 is modulated by zinc binding and disulfide bond formation. Cell. 2014;157:1203-15 pubmed publisher
    ..of a complex comprising the photolyase homology region of mouse CRY1 (mCRY1) and a C-terminal mouse PER2 (mPER2) fragment...
  86. Okamura H, Miyake S, Sumi Y, Yamaguchi S, Yasui A, Muijtjens M, et al. Photic induction of mPer1 and mPer2 in cry-deficient mice lacking a biological clock. Science. 1999;286:2531-4 pubmed
    ..As shown here, cyclic expression of the clock genes mPer1 and mPer2 (mammalian Period genes 1 and 2) in the suprachiasmatic nucleus and peripheral tissues is abolished and mPer1 and ..
  87. Akashi M, Hayasaka N, Yamazaki S, Node K. Mitogen-activated protein kinase is a functional component of the autonomous circadian system in the suprachiasmatic nucleus. J Neurosci. 2008;28:4619-23 pubmed publisher
    ..Furthermore, MAPK inhibition attenuates autonomous circadian neuronal firing rhythms in the SCN. Thus, our data suggest that light-independent MAPK activity contributes to the robustness of the SCN autonomous circadian system. ..
  88. Chaudhury D, Loh D, Dragich J, Hagopian A, Colwell C. Select cognitive deficits in vasoactive intestinal peptide deficient mice. BMC Neurosci. 2008;9:63 pubmed publisher
    ..Together these data suggest that the neuropeptide VIP regulates the recall of at least one learned behavior but does not impact the circadian regulation of this behavior. ..
  89. Maier B, Wendt S, Vanselow J, Wallach T, Reischl S, Oehmke S, et al. A large-scale functional RNAi screen reveals a role for CK2 in the mammalian circadian clock. Genes Dev. 2009;23:708-18 pubmed publisher
    ..In particular, phosphorylation of the key circadian protein PER2 precisely controls the period and phase of circadian oscillations...
  90. Chen R, Schirmer A, Lee Y, Lee H, Kumar V, Yoo S, et al. Rhythmic PER abundance defines a critical nodal point for negative feedback within the circadian clock mechanism. Mol Cell. 2009;36:417-30 pubmed publisher
    ..Furthermore, constitutive expression of PER2 in the brain and SCN of transgenic mice caused a complete loss of behavioral circadian rhythms in a conditional and ..
  91. Grimaldi B, Bellet M, Katada S, Astarita G, Hirayama J, Amin R, et al. PER2 controls lipid metabolism by direct regulation of PPAR?. Cell Metab. 2010;12:509-20 pubmed publisher
    Accumulating evidence highlights intriguing interplays between circadian and metabolic pathways. We show that PER2 directly and specifically represses PPAR?, a nuclear receptor critical in adipogenesis, insulin sensitivity, and ..
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