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Mammalian circadian

Yingbin Zhong, Qiang Ye, Chengyan Chen, Mingyong Wang, Han Wang
EZH2 is a subunit of polycomb repressive complex 2 (PRC2) that silences gene transcription via H3K27me3 and was shown to be essential for mammalian liver circadian regulation and hematopoiesis through gene silencing. Much less, however, is known about how Ezh2 acts in live zebrafish. Here, we show that zebrafish ezh2 is regulated directly by the circadian clock via both E-box and RORE motif, while core circadian clock genes per1a, per1b, cry1aa and cry1ab are down-regulated in ezh2 null mutant and ezh2 morphant zebrafish, and either knockdown or overexpression of ezh2 alters locomotor rhythms, indicating that Ezh2 is required for zebrafish circadian regulation...
February 13, 2018: Nucleic Acids Research
Dorjsuren Battogtokh, Shihoko Kojima, John J Tyson
In recent years, it has become increasingly apparent that antisense transcription plays an important role in the regulation of gene expression. The circadian clock is no exception: an antisense transcript of the mammalian core-clock gene PERIOD2 (PER2), which we shall refer to as Per2AS RNA, oscillates with a circadian period and a nearly 12 h phase shift from the peak expression of Per2 mRNA. In this paper, we ask whether Per2AS plays a regulatory role in the mammalian circadian clock by studying in silico the potential effects of interactions between Per2 and Per2AS RNAs on circadian rhythms...
February 15, 2018: PLoS Computational Biology
Deborah A Hursh, Brian G Stultz
Zinc finger in the cerebellum (Zic) proteins are a family of transcription factors with multiple roles during development, particularly in neural tissues. The founding member of the Zic family is the Drosophila odd-paired (opa) gene. The Opa protein has a DNA binding domain containing five Cys2His2-type zinc fingers and has been shown to act as a sequence-specific DNA binding protein. Opa has significant homology to mammalian Zic1, Zic2, and Zic3 within the zinc finger domain and in two other conserved regions outside that domain...
2018: Advances in Experimental Medicine and Biology
Yong Hoon Kim, Sajid A Marhon, Yuxiang Zhang, David J Steger, Kyoung-Jae Won, Mitchell A Lazar
Mammalian physiology exhibits 24-hour cyclicity due to circadian rhythms of gene expression controlled by transcription factors (TF) that comprise molecular clocks. Core clock TFs bind to the genome at enhancer sequences to regulate circadian gene expression, but not all binding sites are equally functional. Here we demonstrate that circadian gene expression in mouse liver is controlled by rhythmic chromatin interactions between enhancers and promoters. Rev-erbα, a core repressive TF of the clock, opposes functional loop formation between Rev-erbα-regulated enhancers and circadian target gene promoters by recruitment of the NCoR-HDAC3 corepressor complex, histone deacetylation, and eviction of the elongation factor BRD4 and the looping factor MED1...
February 8, 2018: Science
Jingkui Wang, Laura Symul, Jake Yeung, Cédric Gobet, Jonathan Sobel, Sarah Lück, Pål O Westermark, Nacho Molina, Felix Naef
The mammalian circadian clock coordinates physiology with environmental cycles through the regulation of daily oscillations of gene expression. Thousands of transcripts exhibit rhythmic accumulations across mouse tissues, as determined by the balance of their synthesis and degradation. While diurnally rhythmic transcription regulation is well studied and often thought to be the main factor generating rhythmic mRNA accumulation, the extent of rhythmic posttranscriptional regulation is debated, and the kinetic parameters (e...
February 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jarrod Shilts, Guanhua Chen, Jacob J Hughey
The ubiquitous daily rhythms in mammalian physiology are guided by progression of the circadian clock. In mice, systemic disruption of the clock can promote tumor growth. In vitro, multiple oncogenes can disrupt the clock. However, due to the difficulties of studying circadian rhythms in solid tissues in humans, whether the clock is disrupted within human tumors has remained unknown. We sought to determine the state of the circadian clock in human cancer using publicly available transcriptome data. We developed a method, called the clock correlation distance (CCD), to infer circadian clock progression in a group of samples based on the co-expression of 12 clock genes...
2018: PeerJ
Narin Ozturk, Dilek Ozturk, Zeliha Pala-Kara, Engin Kaptan, Serap Sancar-Bas, Nurten Ozsoy, Suzan Cinar, Gunnur Deniz, Xiao-Mei Li, Sylvie Giacchetti, Francis Lévi, Alper Okyar
The circadian timing system controls many biological functions in mammals including xenobiotic metabolism, detoxification, cell proliferation, apoptosis and immune functions. Everolimus is a mammalian target of rapamycin inhibitor, whose immunosuppressant properties are both desired in transplant patients and unwanted in cancer patients, where it is indicated for its antiproliferative efficacy. Here we sought whether everolimus circadian timing would predictably modify its immunosuppressive effects so as to optimize this drug through timing...
February 5, 2018: Chronobiology International
Mino D C Belle, Casey O Diekman
Neuronal oscillations of the brain, such as those observed in the cortices and hippocampi of behaving animals and humans, span across wide frequency bands, from slow delta waves (0.1 Hz) to ultra-fast ripples (600 Hz). Here, we focus on ultra-slow neuronal oscillators in the hypothalamic suprachiasmatic nuclei (SCN), the master daily clock that operates on interlocking transcription-translation feedback loops to produce circadian rhythms in clock gene expression with a period of near 24 hours (<0.001 Hz)...
February 3, 2018: European Journal of Neuroscience
Kelin Wheaton, Sydney Aten, Lucas Sales Queiroz, Kyle Sullivan, John Oberdick, Kari R Hoyt, Karl Obrietan
The circadian timing system influences the functional properties of most, if not all, physiological processes. Central to the mammalian timing system is the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN functions as a 'master clock' that sets the phasing of ancillary circadian oscillator populations found throughout the body. Further, via an entraining input from the retina, the SCN ensures that the clock oscillators are synchronized to the daily light/dark cycle. A critical component of the SCN timing and entrainment systems is the p44/42 mitogen-activated protein kinase (ERK/MAPK) pathway...
January 31, 2018: European Journal of Neuroscience
Charles S Goldsmith, Sam Moon Kim, Nirmala Karunarathna, Nichole Neuendorff, L Gerard Toussaint, David J Earnest, Deborah Bell-Pedersen
BACKGROUND: The circadian clock is the basis for biological time keeping in eukaryotic organisms. The clock mechanism relies on biochemical signaling pathways to detect environmental stimuli and to regulate the expression of clock-controlled genes throughout the body. MAPK signaling pathways function in both circadian input and output pathways in mammals depending on the tissue; however, little is known about the role of p38 MAPK, an established tumor suppressor, in the mammalian circadian system...
January 10, 2018: BMC Cancer
Min Yi, Hekai Li, Zhiye Wu, Jianyun Yan, Qicai Liu, Caiwen Ou, Minsheng Chen
Human neuropeptide Y (hNPY) is one of the most widely expressed neurotransmitters in the human central and peripheral nervous systems. It consists of 36 highly conserved amino acid residues, and was first isolated from the porcine hypothalamus in 1982. While it is the most recently discovered member of the pancreatic polypeptide family (which includes neuropeptide Y, gut-derived hormone peptide YY, and pancreatic polypeptide), NPY is the most abundant peptide found in the mammalian brain. In order to exert particular functions, NPY needs to bind to the NPY receptor to activate specific signaling pathways...
2018: Cellular Physiology and Biochemistry
Teruya Tamaru, Ken Takamatsu
Circadian clocks dictate various physiological functions by brain SCN (a central clock) -orchestrating the temporal harmony of peripheral clocks of tissues/organs in the whole body, with adaptability to environments by resetting their timings. Dysfunction of this circadian adaptation system (CAS) occasionally causes/exacerbates diseases. CAS is based on cell-autonomous molecular clocks, which oscillate via a core transcriptional/translational feedback loop with clock genes/proteins, e.g., BMAL1: CLOCK circadian transcription driver and CRY1/2 and PER1/2 suppressors, and is modulated by various regulatory loops including clock protein modifications...
January 3, 2018: Neurochemistry International
Alexandra J Trott, Jerome S Menet
The mammalian circadian clock relies on the transcription factor CLOCK:BMAL1 to coordinate the rhythmic expression of 15% of the transcriptome and control the daily regulation of biological functions. The recent characterization of CLOCK:BMAL1 cistrome revealed that although CLOCK:BMAL1 binds synchronously to all of its target genes, its transcriptional output is highly heterogeneous. By performing a meta-analysis of several independent genome-wide datasets, we found that the binding of other transcription factors at CLOCK:BMAL1 enhancers likely contribute to the heterogeneity of CLOCK:BMAL1 transcriptional output...
January 4, 2018: PLoS Genetics
Robert L Spencer, Lauren E Chun, Matthew J Hartsock, Elizabeth R Woodruff
Glucocorticoid hormones are a powerful mammalian systemic hormonal signal that exerts regulatory effects on almost every cell and system of the body. Glucocorticoids act in a circadian and stress-directed manner to aid in adaptation to an ever-changing environment. Circadian glucocorticoid secretion provides for a daily waxing and waning influence on target cell function. In addition, the daily circadian peak of glucocorticoid secretion serves as a timing signal that helps entrain intrinsic molecular clock phase in tissue cells distributed throughout the body...
December 26, 2017: Frontiers in Neuroendocrinology
Motoki Nose, Atsushi Tokuoka, Tetsuya Bando, Kenji Tomioka
The timeless2 (tim2) gene is an insect orthologue of the mammalian clock gene Timeless (mTim). Although its functional role has been extensively studied in mammals, little is known regarding its role in insects. In the present study, we obtained tim2 cDNA (Gb'tim2) from the cricket Gryllus bimaculatus and characterized its functional role in embryonic development, egg production, and circadian rhythms. Gb'tim2 gave rise to a 1432 amino acid protein, and showed approximately 65% homology to that of Drosophila melanogaster...
December 26, 2017: Journal of Insect Physiology
Motomi Tainaka, Masao Doi, Yuichi Inoue, Iori Murai, Hitoshi Okamura
It is not known whether the endogenous mammalian core clock proteins sustain measurable oscillations in cells in culture where de novo translation is pharmacologically inhibited. We studied here the mammalian core clock protein PER2, which undergoes robust circadian oscillations in both abundance and phosphorylation. With a newly developed antibody that enables tracing the endogenous PER2 protein oscillations over circadian cycles with cultured mouse embryonic fibroblast cells, we provide evidence that PER2 does not persist noticeable circadian rhythms when translation is inhibited...
December 28, 2017: Chronobiology International
Charna Dibner, Ueli Schibler
Already in 1729 Jean-Jacques d'Ortous de Mairan, a French astronomer, noticed that the mimosa plants in his backyard opened and closed their leaves at similar times during the day. Intriguingly, these daily cycles of leaf movements persisted in plants kept in nearly constant darkness, and de Mairan thus concluded that they must be driven by endogenous clocks rather than environmental light-dark cycles. In the meantime self-sustained circadian oscillators have been found in nearly all light-sensitive organisms from cyanobacteria to mammals...
December 28, 2017: Acta Physiologica
Min Yue, Yu Yang, Gai Li Guo, Xi Ming Qin
The circadian clocks are vital to many organisms for their survival and adaption to the surrounding environment. More and more people are interested in the circadian clock and related researches. One of the key characteristics of this endogenous clock is its periodicity. Mechanisms underlying the mammalian circadian rhythms with ~24 h periodicity involve interlocked transcriptional and translational feedback loops. The circadian clock system in mammals consists of hierarchical structures, with the suprachiasmatic nucleus (SCN) as the central pacemaker and peripheral oscillators in other organs...
December 20, 2017: Yi Chuan, Hereditas
Chaojuan Zhu, Yunyun Xu, Yonghong Duan, Wei Li, Li Zhang, Yang Huang, Wei Zhao, Yutong Wang, Junjie Li, Ting Feng, Xiaomei Li, Xuehui Hu, Wen Yin
Melatonin is an important hormone for regulating mammalian circadian biology and cellular homeostasis. Recent evidence has shown that melatonin exerts anti-nociception effects in both animals and humans. However, according to clinical trials, the anti-nociception effects of melatonin are still controversial. The aim of this meta-analysis was to investigate the anti-nociception effects of melatonin premedication. The primary outcome was the effects of melatonin on pain intensity. The secondary outcomes included the number of patients with analgesic requirements, total analgesic consumption, and brain-derived neurotrophic factor (BDNF) levels...
November 21, 2017: Oncotarget
Kun-Ruey Shieh, Rong-Jie Chen, Shu-Chuan Yang
The diurnal rhythm is the common event in nature and specially shows in the behavioral patterns. Using the infrared sensor or photo beam detector to detect this 24-h rhythmicity in behaviors of mammalian, including in the rats and mice, is also the common way. The photo-sensory detecting mean is friendly and its advantage is unrestricted by light density and light-dark transition. However, this kind of equipment is cost-expensive and uneasy to fit for home cage in rodents. In this study, we tried to use the video-tracking system to detect the rhythmic activity of rats in their home cages...
December 15, 2017: Chinese Journal of Physiology
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