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ABSTRACT: The molecular players of circadian clock oscillation have been identified and extensively characterized. The epigenetic mechanisms behind the circadian gene expression control has also been recently studied, although there are still details to be illucidated. In this review, we briefly summarize the current understanding of the mammalian clock. We also provide evidence for the lack of circadian oscillation in particular cell types. As the circadian clock has intimate interaction with the various cellular functions in different type of cells, it must have plasticity and specicity in its operation within different epigenetic environments. The lack of circadian oscillation in certain cells provide an unique opportunity to study the required epigenetic environment in the cell that permit circadian oscillation and to idenfify key influencing factors for proper clock function. How epigenetic mechansims, including DNA methylaiton and chromatin modifications, participate in control of clock oscillation still awaits future studies at the genomic scale.
Genetics research international. 01/2012; 2012:845429.
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ABSTRACT: The cellular circadian clock and systemic cues drive rhythmicity in the transcriptome of adult peripheral tissues. However, the oscillating status of the circadian clocks in fetal tissues, and their response to maternal cues, are less clear. Most clock genes do not cycle in fetal livers from mice and rats, although tissue level rhythms rapidly emerge when fetal mouse liver explants are cultured in vitro. Thus, in the fetal mouse liver, the circadian clock does not oscillate at the cellular level (but is induced to oscillate in culture). To gain a comprehensive overview of the clock status in the fetal liver during late gestation, we performed microarray analyses on fetal liver tissues. In the fetal liver we did not observe circadian rhythms of clock gene expression or many other transcripts known to be rhythmically expressed in the adult liver. Nevertheless, JTK_CYCLE analysis identified some transcripts in the fetal liver that were rhythmically expressed, albeit at low amplitudes. Upon data filtering by coefficient of variation, the expression levels for transcripts related to pancreatic exocrine enzymes and zymogen secretion were found to undergo synchronized daily fluctuations at high amplitudes. These results suggest that maternal cues influence the fetal liver, despite the fact that we did not detect circadian rhythms of canonical clock gene expression in the fetal liver. These results raise important questions on the role of the circadian clock, or lack thereof, during ontogeny.
PLoS ONE 01/2012; 7(2):e30781. · 4.09 Impact Factor
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ABSTRACT: Microarray transcriptome analyses of fetal mouse liver did not detect circadian expression rhythms of clock genes or clock-controlled genes, although some rhythmic transcripts that were likely not driven by endogenous cellular clocks were identified. This finding reveals a key distinction between the circadian oscillators in fetal and adult mouse livers. Thus, in this study, the transcriptomes of fetal and adult livers were systematically compared to identify differences in the gene expression profiles between these two developmental stages. Approximately 1000 transcripts were differentially enriched between the fetal and adult livers. These transcripts represent genes with cellular functions characteristic of distinct developmental stages. Clock genes were also differentially expressed between the fetal and adult livers. Developmental differences in liver gene expression might have contributed to the differences in oscillation status and functional states of the cellular circadian clock between fetal and adult livers.
PLoS ONE 01/2012; 7(2):e31292. · 4.09 Impact Factor