Rhythmic Expression of
            <i>timeless</i>
            : A Basis for Promoting Circadian Cycles in
            <i>period</i>
            Gene Autoregulation

Sehgal, Amita; Rothenfluh, Adrian; Hunter-Ensor, Melissa; Chen, Yifeng; Myers, Michael P.; Young, Michael W.

doi:10.1126/science.270.5237.808

Cited by 326 publications

(207 citation statements)

References 19 publications

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“…3B, group I). This distribution also is similar to the phases of the classical core circadian genes (10,26,(30)(31)(32)(33)(34), which are under transcriptional regulation and all present within group I. The nascent and mRNA cycling phases of individual group I genes also are essentially identical ( Fig.…”

Section: Resultssupporting

confidence: 50%

Nascent-Seq analysis of Drosophila cycling gene expression

Rodriguez

Tang

Khodor

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

100

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Rhythmic mRNA expression is a hallmark of circadian biology and has been described in numerous experimental systems including mammals. A small number of core clock gene mRNAs and a much larger number of output mRNAs are under circadian control. The rhythmic expression of core clock genes is regulated at the transcriptional level, and this regulation is important for the timekeeping mechanism. However, the relative contribution of transcriptional and posttranscriptional regulation to global circadian mRNA oscillations is unknown. To address this issue in Drosophila, we isolated nascent RNA from adult fly heads collected at different time points and subjected it to high-throughput sequencing. mRNA was isolated and sequenced in parallel. Some genes had cycling nascent RNAs with no cycling mRNA, caused, most likely, by light-mediated read-through transcription. Most genes with cycling mRNAs had significant nascent RNA cycling amplitudes, indicating a prominent role for circadian transcriptional regulation. However, a considerable fraction had higher mRNA amplitudes than nascent RNA amplitudes. The same comparison for core clock gene mRNAs gives rise to a qualitatively similar conclusion. The data therefore indicate a significant quantitative contribution of posttranscriptional regulation to mRNA cycling.Nas-seq | chromatin dynamics T he circadian clock controls the rhythmic expression of thousands of genes. These mRNAs mediate the oscillation of numerous biochemical, physiological, and behavioral functions. Although inconsistency among microarray datasets has made it difficult to identify a definitive set of mRNA cyclers in Drosophila, there is good agreement on a small number of robust cycling mRNAs (see below). Moreover, it appears that a much larger number of cycling mRNAs exist within circadian neurons (1), and thousands of mRNAs have been shown to oscillate within individual tissues in mammals (2-5).Cycling mRNAs are dependent on a functional pacemaker (6, 7), but most probably are regulated only indirectly by the core circadian clock (8). In flies, this mechanism consists of the CLOCK and CYCLE heterodimer (CLK/CYC), which drives the rhythmic transcription of its repressor protein genes period and timeless (9). After translation, the proteins PER and TIM decrease their own transcription by inhibiting the activity of CLK/ CYC (10-12). A set of largely orthologous proteins (CLK, BMAL1, PER, and CRYPTOCHROME) functions similarly in mammals. Although posttranslational regulation of these transcription factors makes a major contribution to core clock function (13-19), there is evidence that transcriptional regulation also is important for circadian timing. For example, flies with enhanced CLK/CYC-mediated transcription have unusually high levels of per mRNA and significantly shorter periods (20).The core clock model drives the assumption that the large population of cycling mRNAs-the hundreds or thousands of output mRNAs under circadian regulation-is also under transcriptional regulation. However, it is not known w...

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Section: Resultssupporting

confidence: 50%

Nascent-Seq analysis of Drosophila cycling gene expression

Rodriguez

Tang

Khodor

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

100

View full text Add to dashboard Cite

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“…Genes per and tim are transcriptionally regulated in a cyclic manner. Transcripts of both genes are present early in the day but the highest levels are found late in the day and at the beginning of the night [35][36][37]. PER and TIM proteins accumulate during the night and form a heterodimer that moves into the nucleus to bind to transcription factors Clock (CLK) and Cycle (CYC).…”

Section: Case Studies In the Conservation Of Gene Function In Behaviourmentioning

confidence: 99%

Conservation of gene function in behaviour

Reaume

Sokolowski

2011

Phil. Trans. R. Soc. B

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Behaviour genetic research has shown that a given gene or gene pathway can influence categorically similar behaviours in different species. Questions about the conservation of gene function in behaviour are increasingly tractable. This is owing to the surge of DNA and 'omics data, bioinformatic tools, as well as advances in technologies for behavioural phenotyping. Here, we discuss how gene function, as a hierarchical biological phenomenon, can be used to examine behavioural homology across species. The question can be addressed independently using different levels of investigation including the DNA sequence, the gene's position in a genetic pathway, spatial-temporal tissue expression and neural circuitry. Selected examples from the literature are used to illustrate this point. We will also discuss how qualitative and quantitative comparisons of the behavioural phenotype, its function and the importance of environmental and social context should be used in cross-species comparisons. We conclude that (i) there are homologous behaviours, (ii) they are hard to define and (iii) neurogenetics and genomics investigations should help in this endeavour.

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“…Two most intensely studied clock genes in D. melanogaster are period (per) and timeless (tim). Both genes encode RNAs that cycle with a circadian rhythm, such that RNA levels are high at the end of the day/beginning of the night (Hardin et al 1990;Sehgal et al 1995). The per and tim gene products, proteins PER and TIM, also cycle and begin accumulating in the middle of the night.…”

Section: The Molecular Components Of Circadian Clocksmentioning

confidence: 99%

Peripheral clocks and their role in circadian timing: insights from insects

Giebułtowicz

2001

Phil. Trans. R. Soc. Lond. B

104

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Impressive advances have been made recently in our understanding of the molecular basis of the cellautonomous circadian feedback loop; however, much less is known about the overall organization of the circadian systems. How many clocks tick in a multicellular animal, such as an insect, and what are their roles and the relationships between them? Most attempts to locate clock-containing tissues were based on the analysis of behavioural rhythms and identi¢ed brain-located timing centres in a variety of animals. Characterization of several essential clock genes and analysis of their expression patterns revealed that molecular components of the clock are active not only in the brain, but also in many peripheral organs of Drosophila and other insects as well as in vertebrates. Subsequent experiments have shown that isolated peripheral organs can maintain self-sustained and light sensitive cycling of clock genes in vitro. This, together with earlier demonstrations that physiological output rhythms persist in isolated organs and tissues, provide strong evidence for the existence of functionally autonomous local circadian clocks in insects and other animals. Circadian systems in complex animals may include many peripheral clocks with tissue-speci¢c functions and a varying degree of autonomy, which seems to be correlated with their sensitivity to external entraining signals.

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Rhythmic Expression of timeless : A Basis for Promoting Circadian Cycles in period Gene Autoregulation

Cited by 326 publications

References 19 publications

Nascent-Seq analysis of Drosophila cycling gene expression

Nascent-Seq analysis of Drosophila cycling gene expression

Conservation of gene function in behaviour

Peripheral clocks and their role in circadian timing: insights from insects

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