CLOCK and NPAS2 have overlapping roles in the circadian oscillation of arylalkylamineN-acetyltransferase mRNA in chicken cone photoreceptors (original) (raw)
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Molecular biological approach to the circadian clock mechanism
Neuroscience Research the Official Journal of the Japan Neuroscience Society, 1995
Many circadian phenomena have been described in a diverse range of species, from single cellular organisms to higher species of plants and animals. From several lines of evidence from Drosophila and Neurospora, the oscillation of the circadian clock seems to involve cycling gene expression. Although a great deal of information concerning the anatomy, neurophysiology and neurochemistry of circadian pacemakers has been obtained over the last decade, molecular and cellular approaches to this problem have only just begun. I will summarize recent progress of the molecular biological approach to the circadian clock mechanism. Finally, the importance of' transcription factors to envision the common mechanism of circadian clock in the diverged species will be discussed considering with the existence of a hypothetical 'Time Box'.
Animal clocks: a multitude of molecular mechanisms for circadian timekeeping
Wiley Interdisciplinary Reviews: RNA, 2011
Studies in various model organisms reveal that the expression level of a substantial part of the transcriptome and the proteome exhibits regular daily oscillations. These oscillations are translated to physiological and behavioral rhythms allowing organisms to efficiently anticipate and respond to the daily and seasonally changing environment (e.g., temperature and light). A rather small subset of evolutionary conserved genes drives these oscillations and constitutes the core molecular circadian clock. Here, we review the multiple mechanisms that coexist at various molecular and cellular levels and are involved in the metazoan circadian clock, including transcription/translation negative feedback loops, post-transcriptional and post-translational modifications, intracellular translocation, and intercellular signaling.
Molecular components of the mammalian circadian clock
Human Molecular Genetics, 2006
Circadian rhythms are 24-h oscillations in behavior and physiology, which are internally generated and function to anticipate the environmental changes associated with the solar day. A conserved transcriptional -translational autoregulatory loop generates molecular oscillations of 'clock genes' at the cellular level. In mammals, the circadian system is organized in a hierarchical manner, in which a master pacemaker in the suprachiasmatic nucleus (SCN) regulates downstream oscillators in peripheral tissues. Recent findings have revealed that the clock is cell-autonomous and self-sustained not only in a central pacemaker, the SCN, but also in peripheral tissues and in dissociated cultured cells. It is becoming evident that specific contribution of each clock component and interactions among the components vary in a tissue-specific manner. Here, we review the general mechanisms of the circadian clockwork, describe recent findings that elucidate tissue-specific expression patterns of the clock genes and address the importance of circadian regulation in peripheral tissues for an organism's overall well-being.
Journal of Neurochemistry, 2003
The molecular core of the vertebrate circadian clock is a set of clock genes, whose products interact to control circadian changes in physiology. These clock genes are expressed in all tissues known to possess an endogenous self-sustaining clock, and many are also found in peripheral tissues. In the present study, the expression patterns of two clock genes, cBmal1 and cMOP4, were examined in the chicken, a useful model for analysis of the avian circadian system. In two tissues which contain endogenous clocks -the pineal gland and retina -circadian fluctuations of both cBmal1 and cMOP4 mRNAs were observed to be synchronous; highest levels occurred at Zeitgeber time 12. Expression of these genes is also rhythmic in several peripheral tissues; however, the phases of these rhythms differ from those in the pineal gland and retina: in the liver the peaks of cMOP4 and cBmal1 mRNAs are delayed 4-8 h and in the heart they are advanced by 4 h, relative to those in the pineal gland and retina. These results provide the first temporal characterization of cBmal1 and cMOP4 mRNAs in avian tissues: their presence in avian peripheral tissues indicates they may influence temporal features of daily rhythms in biochemical, physiological, and behavioral functions at these sites. helix-loop-helix PER-ARNT-SIM; Bmal1, brain and muscle ARNT-like protein 1; LD, light-dark; MOP4, member of the PAS super family protein 4; NPAS2, neuronal PAS domain protein 2; RT-PCR, reverse transcription-polymerase chain reaction; SCN, suprachiasmatic nucleus; ZT, Zeitgeber time.
Photoperiodic Modulation of Clock Gene Expression in the Avian Premammillary Nucleus
Journal of Neuroendocrinology, 2010
The seasonal rhythms of endocrine and metabolic physiological processes in breeding birds are known to be synchronised by the perception of environmental cues such as day length (1, 2). The timing of neuroendocrine events important for avian reproduction is set by internal clocks and by deep brain photoreceptors that receive and integrate this photoperiodic information (3, 4). Shifts in timing as a result of input from these structures will result in the modulation of endocrine-related gene expression, which will drive the function of the reproductive organs.
The systemic control of circadian gene expression
Diabetes, Obesity and Metabolism, 2015
The mammalian circadian timing system consists of a central pacemaker in the brain's suprachiasmatic nucleus (SCN) and subsidiary oscillators in nearly all body cells. The SCN clock, which is adjusted to geophysical time by the photoperiod, synchronizes peripheral clocks through a wide variety of systemic cues. The latter include signals depending on feeding cycles, glucocorticoid hormones, rhythmic blood-borne signals eliciting daily changes in actin dynamics and serum response factor (SRF) activity, and sensors of body temperature rhythms, such as heat shock transcription factors and the cold-inducible RNA-binding protein CIRP. To study these systemic signalling pathways, we designed and engineered a novel, highly photosensitive apparatus, dubbed RT-Biolumicorder. This device enables us to record circadian luciferase reporter gene expression in the liver and other organs of freely moving mice over months in real time. Owing to the multitude of systemic signalling pathway involved in the phase resetting of peripheral clocks the disruption of any particular one has only minor effects on the steady state phase of circadian gene expression in organs such as the liver. Nonetheless, the implication of specific pathways in the synchronization of clock gene expression can readily be assessed by monitoring the phase-shifting kinetics using the RT-Biolumicorder.
Timing of circadian genes in mammalian tissues
Scientific Reports, 2014
Circadian clocks are endogenous oscillators driving daily rhythms in physiology. The cell-autonomous clock is governed by an interlocked network of transcriptional feedback loops. Hundreds of clock-controlled genes (CCGs) regulate tissue specific functions. Transcriptome studies reveal that different organs (e.g. liver, heart, adrenal gland) feature substantially varying sets of CCGs with different peak phase distributions. To study the phase variability of CCGs in mammalian peripheral tissues, we develop a core clock model for mouse liver and adrenal gland based on expression profiles and known cis-regulatory sites. 'Modulation factors' associated with E-boxes, ROR-elements, and D-boxes can explain variable rhythms of CCGs, which is demonstrated for differential regulation of cytochromes P450 and 12 h harmonics. By varying model parameters we explore how tissue-specific peak phase distributions can be generated. The central role of E-boxes and ROR-elements is confirmed by analysing ChIP-seq data of BMAL1 and REV-ERB transcription factors.
Genetics of Circadian Rhythms in Mammalian Model Organisms
Genetics of Circadian Rhythms, 2011
The mammalian circadian system is a complex hierarchical temporal network which is organized around an ensemble of uniquely coupled cells comprising the principal circadian pacemaker in the suprachiasmatic nucleus of the hypothalamus. This central pacemaker is entrained each day by the environmental light/dark cycle and transmits synchronizing cues to cell-autonomous oscillators in tissues throughout the body. Within cells of the central pacemaker and the peripheral tissues, the underlying molecular mechanism by which oscillations in gene expression occur involves interconnected feedback loops of transcription and translation. Over the past 10 years we have learned much regarding the genetics of this system, including how it is particularly resilient when challenged by single-gene mutations, how accessory transcriptional loops enhance the robustness of oscillations, how epigenetic mechanisms contribute to the control of circadian gene expression, and how, from coupled neuronal networks, emergent clock properties arise. Here we will explore the genetics of the mammalian circadian system from cell-autonomous molecular oscillations, to interactions among central and peripheral oscillators and ultimately, to the daily rhythms of behavior observed in the animal.