• Proceedings of the KSAR Conference
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• 2004.06a
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• pp.261-261
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• 2004

Circadian rhythms, which measure time about 24 hours, are generated by one of the most ubiquitous and well investigated timing system. More recently, circadian clock gene expression has been reported in various peripheral tissues. If a circadian clock is functioning in the testis, expression of clock genes should be observed in this tissue. To resolve this issue, we examined the expression of circadian clock genes in the testis. (omitted)

• Journal of Life Science
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• v.25 no.11
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• pp.1304-1310
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• 2015

The period circadian clock gene 3 (PER3) plays a role in the mammalian circadian clocksystem. A regular exercise regime may affect the PER3 transcription in skeletal muscle. Although the effects of day length on circadian and circannual processes are well established in humans and mice, the influence of exercise on these processes in the horse has not been investigated. The present study investigated the expression of the PER3 gene following exercise in a thoroughbred breed of Korean horse. In addition, a comprehensive in silico nonsynonymous single nucleotide polymorphism (nsSNP) analysis of the horse PER3 gene and predicted effects of nsSNPs on proteins were examined. The expression of PER3 in skeletal muscle was significantly upregulated after exercise. Four nsSNPs were functionally annotated and analyzed by computational prediction. The total free energy and RMSD values of PER3 gene showed causative mutations. The results showed that nsSNP s395916798 (G72R) was associated with residues that have stabilizing effects on structure and function of PER3 gene. This study documented role of PER3 gene in phenotypic adaptation related to exercise in skeletal muscle. Further, the SNPs in PER3 could serve as useful biomarkers of early recovery after exercise in racehorses.

• BMB Reports
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• v.49 no.11
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• pp.587-589
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• 2016

The circadian clock system enables organisms to anticipate the rhythmic environmental changes and to manifest behavior and physiology at advantageous times of the day. Transcriptional/translational feedback loop (TTFL) is the basic feature of the eukaryotic circadian clock and is based on the rhythmic association of circadian transcriptional activator and repressor. In Drosophila, repression of dCLOCK/CYCLE (dCLK/CYC) mediated transcription by PERIOD (PER) is critical for inducing circadian rhythms of gene expression. Pacemaker neurons in the brain control specific circadian behaviors upon environmental timing cues such as light and temperature cycle. We show that amino acids 657-707 of dCLK are important for the transcriptional activation and the association with PER both in vitro and in vivo. Flies expressing dCLK lacking AA657-707 in $Clk^{out}$ genetic background, homologous to the mouse Clock allele where exon 19 region is deleted, display pacemaker-neuron-dependent perturbation of the molecular clockwork. The molecular rhythms in light-cycle-sensitive pacemaker neurons such as ventral lateral neurons ($LN_vs$) were significantly disrupted, but those in temperature-cycle-sensitive pacemaker neurons such as dorsal neurons (DNs) were robust. Our results suggest that the dCLK-controlled TTFL diversify in a pacemaker-neuron-dependent manner which may contribute to specific functions such as different sensitivities to entraining cues.

• BMB Reports
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• v.48 no.12
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• pp.677-684
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• 2015

Cardiovascular function is regulated by the rhythmicity of circadian, infradian and ultradian clocks. Specific time scales of different cell types drive their functions: circadian gene regulation at hours scale, activation-inactivation cycles of ion channels at millisecond scales, the heart's beating rate at hundreds of millisecond scales, and low frequency autonomic signaling at cycles of tens of seconds. Heart rate and rhythm are modulated by a hierarchical clock system: autonomic signaling from the brain releases neurotransmitters from the vagus and sympathetic nerves to the heart's pacemaker cells and activate receptors on the cell. These receptors activating ultradian clock functions embedded within pacemaker cells include sarcoplasmic reticulum rhythmic spontaneous Ca²⁺ cycling, rhythmic ion channel current activation and inactivation, and rhythmic oscillatory mitochondria ATP production. Here we summarize the evidence that intrinsic pacemaker cell mechanisms are the end effector of the hierarchical brain-heart circadian clock system.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 2006.10a
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• pp.62-62
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• 2006

• Journal of Life Science
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• v.22 no.8
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• pp.999-1008
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• 2012

The circadian clock is a self-sustaining 24-hour timekeeper that allows organisms to anticipate daily-changing environmental time cues. Circadian clock genes are regulated by a transcriptional-translational feedback loop. In Arabidopsis, LATE ELONGATED HYPOCOTYL (LHY) and CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) transcripts are highly expressed in the morning. Translated LHY and CCA1 proteins repress the expression of the TIMING OF CAB EXPRESSION 1 (TOC1) transcripts, which peaks in the evening. The TOC1 protein elevates the expression of the LHY and CCA1 transcripts, forming a negative feedback loop that is believed to constitute the oscillatory mechanism of the clock. In mammals, the transcription factor protein CLOCK, which is a central component of the circadian clock, was reported to have an intrinsic histone acetyltransferase (HAT) activity, suggesting that histone acetylation is important for core clock mechanisms. However, little is known about the components necessary for the histone acetylation of the Arabidopsis clock-related genes. Here, I report that DET1 (De-Etiolated1) functions as a negative regulator of a key component of the Arabidopsis circadian clock gene LHY in constant dark phases (DD) and is required for the down-regulation of LHY expression through the acetylation of histone 3 (H3Ac). However, the HATs directly responsible for the acetylation of H3 within LHY chromatin need to be identified, and a link connecting the HATs and DET1 protein is still absent.

• Molecules and Cells
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• v.22 no.3
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• pp.275-284
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• 2006

The molecular components that generate and maintain circadian rhythms of physiology and behavior in mammals are present both in the brain (suprachiasmatic nucleus; SCN) and in peripheral tissues. 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. Here we show that loss of the clock gene mPer2 affects forced locomotor performance in mice without altering muscle contractility. A proteomic analysis revealed that the anterior tibialis muscles of the mPer2 knockout mice had higher levels of glycolytic enzymes such as triose phosphate isomerase and enolase than those of either the wild type or mPer1 knockout mice. In addition, the level of expression of HSP90 in the mPer2 mutant mice was also significantly higher than in wildtype mice. These results suggest that the reduced locomotor endurance of the mPer2 knockout mice reflects a greater dependence on anaerobic metabolism under stress conditions, and that the two canonical clock genes, mPer1 and mPer2, play distinct roles in the physiology of skeletal muscle.

• Development and Reproduction
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• v.8 no.1
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• pp.57-64
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• 2004

This study was carried out to examine the expression of the circadian clock genes in the mouse ovary and testis at different developmental stages. Expression of Period1(Per 1), Period2(Per2), Period3(Per3), Cryptochrome1(Cry1), Cyptochrome2(Cry2), Clock Small and Prokineticin1 and Prokineticin2 receptor(Prok1r, Prok2r) genes in mouse ovary was explored by semiquantitative reverse transcription Polymerase chain reaction(RT-PCR) according to the developmental stage(post partum day; ppd 1, 7, 10, 21 and 35). Immunohistochemistry using PER1 antibody was also analyzed. The differential expression pattern of clock genes was presented according to stages of the mouse ovarian development (ppd 1, 7, 10, 21 and 35). In the cases of ovaries, at the starting point of follicle growth at ppd 7 and 10, the clock gene expression patterns were changed vastly. According to the developmental stages, the clock genes were highly expressed at ppd 7 and 10 in mouse testis also. Receptors for Prok2, the circadian output molecule of SCN, were also expressed in ovary at ppd 7 and in testis at ppd 1 and 7, respectively. Immnunohistochemical analysis of PER1 showed positive signals in the cytoplasm of oocytes and granulosa cells. The level or PER1 expression was increased in cells at the spermatogonia and the condensing spermatids. The expression pattern of Perl and localization of PER1 were showed similar patterns according to the developmental stages in ovary and testis. Taken together, it could be observed that the expression of clock genes was highly correlated with gonadal development and germ cell differentiation in mice. Therefore, in this study, circadian programming of the genes in the ovary and testis is strongly imposed across a wide range of core reproductive cycles and normal development of gametes. Although the existence of circadian genes is clearly investigated, further studies on the direct evidence is required for the understanding of the relationship between circadian genes and regulation of gonadal differentiation and germ cell development.

• Proceedings of the Zoological Society Korea Conference
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• 2003.08a
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• pp.165.4-165
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• 2003

No Abstract, See Full Text

• Molecules and Cells
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• v.42 no.4
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• pp.301-312
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• 2019

Post-transcriptional regulation underlies the circadian control of gene expression and animal behaviors. However, the role of mRNA surveillance via the nonsense-mediated mRNA decay (NMD) pathway in circadian rhythms remains elusive. Here, we report that Drosophila NMD pathway acts in a subset of circadian pacemaker neurons to maintain robust 24 h rhythms of free-running locomotor activity. RNA interference-mediated depletion of key NMD factors in timeless-expressing clock cells decreased the amplitude of circadian locomotor behaviors. Transgenic manipulation of the NMD pathway in clock neurons expressing a neuropeptide PIGMENT-DISPERSING FACTOR (PDF) was sufficient to dampen or lengthen free-running locomotor rhythms. Confocal imaging of a transgenic NMD reporter revealed that arrhythmic Clock mutants exhibited stronger NMD activity in PDF-expressing neurons than wild-type. We further found that hypomorphic mutations in Suppressor with morphogenetic effect on genitalia 5 (Smg5) or Smg6 impaired circadian behaviors. These NMD mutants normally developed PDF-expressing clock neurons and displayed daily oscillations in the transcript levels of core clock genes. By contrast, the loss of Smg5 or Smg6 function affected the relative transcript levels of cAMP response element-binding protein B (CrebB) in an isoform-specific manner. Moreover, the overexpression of a transcriptional repressor form of CrebB rescued free-running locomotor rhythms in Smg5-depleted flies. These data demonstrate that CrebB is a rate-limiting substrate of the genetic NMD pathway important for the behavioral output of circadian clocks in Drosophila.