2015
DOI: 10.1074/jbc.m114.605022
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The Zebrafish Period2 Protein Positively Regulates the Circadian Clock through Mediation of Retinoic Acid Receptor (RAR)-related Orphan Receptor α (Rorα)

Abstract: Background: Null mutants for zebrafish period2 were generated to elucidate its functions. Results: Both locomotor activity and expression of key circadian clock genes are disrupted in the period2 mutant zebrafish. Conclusion: Period2 is essential for zebrafish circadian regulation. Significance: Period2 plays a positive role in the zebrafish circadian clock by enhancing bmal1b expression through binding to nuclear receptor Ror␣.

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Cited by 46 publications
(41 citation statements)
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References 79 publications
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“…Given that oscillations of cry1aa and per1b show a phase shift upon treatment with NMR, while the oscillation of per2 remains stable, this should also lead to altered ratios of the protein heterodimers Cry1aa/Per1b and Cry1aa/Per2 in the cytosol of cells. Consequently, also different gene sets should be activated or repressed according to the type of irradiation, in particular when considering that zebrafish per2 is predominantly and essentially involved in the positive regulation of the circadian clock, while per1b exerts a repressive function (Wang et al 2015), and that both play also differential roles in the inflammatory immune response of zebrafish (Ren et al 2018), implicating therefore also an immunomodulatory capacity of NMR irradiation. Interestingly, NMR therapy applied for 4 h did not affect the oscillating promoter activity of per1b ( Figure S4), so that response elements located in the first 3.1 kb of the per1b promoter regions can be excluded from being responsible for the NMR-induced alterations at the level of per1b mRNA.…”
Section: Discussionmentioning
confidence: 99%
“…Given that oscillations of cry1aa and per1b show a phase shift upon treatment with NMR, while the oscillation of per2 remains stable, this should also lead to altered ratios of the protein heterodimers Cry1aa/Per1b and Cry1aa/Per2 in the cytosol of cells. Consequently, also different gene sets should be activated or repressed according to the type of irradiation, in particular when considering that zebrafish per2 is predominantly and essentially involved in the positive regulation of the circadian clock, while per1b exerts a repressive function (Wang et al 2015), and that both play also differential roles in the inflammatory immune response of zebrafish (Ren et al 2018), implicating therefore also an immunomodulatory capacity of NMR irradiation. Interestingly, NMR therapy applied for 4 h did not affect the oscillating promoter activity of per1b ( Figure S4), so that response elements located in the first 3.1 kb of the per1b promoter regions can be excluded from being responsible for the NMR-induced alterations at the level of per1b mRNA.…”
Section: Discussionmentioning
confidence: 99%
“…A 721-bp fragment of the zebrafish col10a1a promoter containing two Sp1 sites was PCR amplified and cloned into the pGL4.17 luciferase vector, named as pcol10a1a-luc. The two Sp1 sites in the col10a1a promoter were mutated, respectively, with the sitedirected mutagenesis as described previously [40], and then pSp1-1mut-luc and pSp1-2mut-luc were constructed. The fulllength cDNA of sp7 was PCR amplified using wild-type zebrafish cDNAs as template and inserted into the pMD19T vector, and then subcloned into pcDNA3.1 tagged with His-Myc.…”
Section: Plasmid Constructionmentioning
confidence: 99%
“…A particular study by Baird et al (2012) found aberrant expression of the Per2 gene in adults with ADHD, and that the amplitude of expression of this gene is correlated with the severity of ADHD symptoms. Furthermore, a recent study by Wang et al (2015) showed that Per2-null mutant zebrafish exhibited reduced locomotor activity. Furthermore, a recent study by Wang et al (2015) showed that Per2-null mutant zebrafish exhibited reduced locomotor activity.…”
Section: Discussionmentioning
confidence: 99%
“…Moreover, mice with targeted mutation of the Per2 gene were showed to have disrupted locomotor activity rhythms (Bae et al 2001). Furthermore, a recent study by Wang et al (2015) showed that Per2-null mutant zebrafish exhibited reduced locomotor activity. Together, the importance of Per2 as a probable hyperactive-specific ADHD genetic risk factor cannot be underscored given the above-mentioned findings.…”
Section: Discussionmentioning
confidence: 99%