Essential and expendable features of the circadian timekeeping mechanism

Hardin, Paul E.

doi:10.1016/j.conb.2006.09.001

Cited by 74 publications

(55 citation statements)

References 48 publications

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“…The isolation of several additional clock genes has helped to refine this mechanism (for review, see Young and Kay 2001;Hardin 2006). For example, some of the more recently identified genes regulate the phosphorylation or dephosphorylation of PER and TIM, affecting PER/TIM subcellular localization and stability (Harms et al 2003;Bae and Edery 2006).…”

Section: Timeless and Temporal Delays In The Circadian Clockmentioning

confidence: 99%

A PER/TIM/DBT Interval Timer forDrosophila's Circadian Clock

Sáez¹,

Meyer²,

Young³

2007

Cold Spring Harbor Symposia on Quantitative Biology

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Circadian rhythms in Drosophila are supported by a negative feedback loop, in which PERIOD (PER) and Timeless (TIM) shut down their own transcription as they translocate once a day from the cytoplasm of clock-containing cells to the nucleus. Period length is partially determined by an interval of cytoplasmic retention of the TIM and PER proteins. To study this process, we examined PER/TIM/Doubletime (DBT) physical interactions and nuclear translocation by imaging individual cultured Drosophila cells. Using live cell video microscopy and green fluorescent protein (GFP) tags, we observed dynamic patterns of stability and localization for DBT, PER, and TIM that resembled those previously found in vivo. These studies suggest that a cytoplasmic interval timer regulates nuclear translocation of these proteins. The cultured cell assay provides a potent system to study interactions among new and known genes involved in the generation of circadian behavior.

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Section: Timeless and Temporal Delays In The Circadian Clockmentioning

confidence: 99%

A PER/TIM/DBT Interval Timer forDrosophila's Circadian Clock

Sáez¹,

Meyer²,

Young³

2007

Cold Spring Harbor Symposia on Quantitative Biology

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“…The current view of the clockwork is two interlocked transcriptional/posttranslational feedback loops comprising a battery of transcriptional activators and repressors (Hardin 2006;Ko and Takahashi 2006). A heterodimeric complex of BMAL1 and either CLOCK or NPAS2 activate the transcription of Period genes (Per1, Per2, and Per3) and Cryptochrome genes (Cry1 and Cry2) by recognizing E-box cis-regulatory elements in their promoters.…”

Section: Nrs Within the Core Clockworkmentioning

confidence: 99%

Nuclear Receptors, Metabolism, and the Circadian Clock

Yang¹,

Lamia²,

Evans³

2007

Cold Spring Harbor Symposia on Quantitative Biology

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As ligand-dependent transcription factors, the nuclear receptor superfamily governs a remarkable array of rhythmic physiologic processes such as metabolism and reproduction. To provide a "molecular blueprint" for nuclear receptor function in circadian biology, we established a diurnal expression profile of all mouse nuclear receptors in critical metabolic tissues. Our finding of broad expression and tissue-specific oscillation of nuclear receptors along with their key target genes suggests that diurnal nuclear receptor expression may contribute to established rhythms in metabolic physiology and that nuclear receptors may be involved in coupling peripheral circadian clocks to divergent metabolic outputs. Conversely, nuclear receptors may serve peripheral clock input pathways, integrating signals from the light-sensing central clock in the suprachiasmatic nucleus and other environmental cues, such as nutrients and xenobiotics. Interplay between the core circadian clock and nuclear receptors may define a large-scale signaling network that links biological timing to metabolic physiology.

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“…In Drosophila, CYC is a bHLH-PAS protein that plays a central role in regulating circadian rhythms via heterodimerization with another bHLH-PAS protein Clock (CLK) (15). In Aedes female mosquitoes, depletion of either CYC or MET by means of RNA interference (RNAi) impaired the circadian activation of Kr-h1 and Hairy genes.…”

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confidence: 99%

bHLH-PAS heterodimer of methoprene-tolerant and Cycle mediates circadian expression of juvenile hormone-induced mosquito genes

Shin

Zou

Saha

et al. 2012

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

114

108

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Juvenile hormone (JH) governs a great diversity of processes in insect development and reproduction. It plays a critical role in controlling the gonadotrophic cycles of female mosquitoes by preparing tissues for blood digestion and egg development. Here, we show that in female Aedes aegypti mosquitoes JH III control of gene expression is mediated by a heterodimer of two bHLH-PAS proteins-the JH receptor methoprene-tolerant (MET) and Cycle (CYC, AAEL002049). We identified Aedes CYC as a MET-interacting protein using yeast two-hybrid screening. Binding of CYC and MET required the presence of JH III. In newly eclosed female mosquitoes, the expression of two JH-responsive genes, Kr-h1 and Hairy, was dependent on both the ratio of light to dark periods and JH III. Their expression was compromised by in vivo RNA interference (RNAi) depletions of CYC, MET, and the steroid receptor coactivator SRC/FISC. Moreover, JH III was not effective in induction of Krh1 and Hairy gene expression in vitro in fat bodies of female mosquitoes with RNAi-depleted CYC, MET or SRC/FISC. A sequence containing an E-box-like motif from the Aedes Kr-h1 gene promoter specifically interacted with a protein complex, which included MET and CYC from the female mosquito fat body nuclear extract. These results indicate that a MET/CYC heterodimer mediates JH III activation of Kr-h1 and Hairy genes in the context of light-dependent circadian regulation in female mosquitoes during posteclosion development. This study provides an important insight into the understanding of the molecular basis of JH action.hormone receptor | insect hormone | transcriptional control M osquitoes serve as vectors of harmful human diseases because blood feeding is required for their egg development; disease pathogens use hematophagous female mosquitoes for obligatory stages of their life cycles. An insect-specific sesquiterpenoid juvenile hormone III (JH III) is essential for a newly eclosed female mosquito to reach a competence stage for blood feeding and egg maturation (1, 2). Although several aspects of the JH III-dependent development have been characterized (3-6), our understanding of molecular mechanisms underlying JH regulation of female mosquito posteclosion development is limited.Methoprene-tolerant (MET), which is a basic helix-loop-helix (bHLH)-Per-Arnt-Sim (PAS) protein, was discovered in Drosophila melanogaster (7), and its role in mediating a JH response has been established (8). MET binds to JH with a high affinity, suggesting that it is the JH receptor (9, 10). As a bHLH protein, MET requires either a homo-or heterodimer partner for its activity (11). Studies in Aedes aegypti, the beetle Tribolium castaneum, and the silkworm Bombyx mori have shown a bHLH-PAS domain-containing steroid receptor coactivator (SRC/FISC/ Taiman) to interact with MET (10,[12][13][14]. Whether, an additional bHLH transcription factor with DNA-binding properties is required as a Met partner remains to be established.Using yeast two-hybrid (Y2H) screening, we identified an Aedes ortholo...

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Essential and expendable features of the circadian timekeeping mechanism

Cited by 74 publications

References 48 publications

A PER/TIM/DBT Interval Timer forDrosophila's Circadian Clock

A PER/TIM/DBT Interval Timer forDrosophila's Circadian Clock

Nuclear Receptors, Metabolism, and the Circadian Clock

bHLH-PAS heterodimer of methoprene-tolerant and Cycle mediates circadian expression of juvenile hormone-induced mosquito genes

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