Functional Role of CREB-Binding Protein in the Circadian Clock System of <i>Drosophila melanogaster</i>

Lim, Chunghun; Lee, Jong Bin; Choi, Changtaek; Kim, Juwon; Doh, Eunjin; Choe, Joonho

doi:10.1128/mcb.02155-06

Cited by 52 publications

(60 citation statements)

References 61 publications

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“…Consistent with our results, a parallel study by Lim et al (34) found a role for nej in the Drosophila circadian clock. From the finding of low expression levels of CLK⅐CYC-dependent genes after constitutive overexpression of nej it was concluded that NEJ acted as a repressor on CLK⅐CYC function.…”

Section: Q7supporting

confidence: 82%

Circadian Transcription Depends on Limiting Amounts of the Transcription Co-activator nejire/CBP

Hung

Maurer

Kay

et al. 2007

Journal of Biological Chemistry

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The circadian clock orchestrates physiological and behavioral activities, including metabolism, neuronal activity, and cell proliferation in synchrony with the environmental cycle of day and night. Here we show that the Drosophila ortholog of the CBP/ p300 family of transcription co-activators, nejire (nej), is an intrinsic component of the circadian clock that performs regulatory functions for circadian controlled transcription. Screening of overexpression mutants revealed that gain of nej function was associated with a loss of behavioral and molecular rhythms. Overexpression of NEJ suppresses the long period phenotype of a mutation in the clock gene period (per). NEJ physically interacts through two binding sites with CLOCK and the CLOCK⅐CYCLE (CLK⅐CYC) complex. Induction of CLK⅐CYC-dependent transcripts upon induction of nej expression from a heat-shock promoter showed that NEJ is limiting. Reduced CLK⅐CYC-mediated transcription in a nej hypomorphic mutant indicates an essential function of NEJ/CBP for CLK⅐CYC activity and a regulation of circadian transcription by availability of the co-activator. Competition for recruitment of NEJ/CBP provides a potential mechanism for cross-talk between circadian transcription and other CBP-dependent physiological processes.The circadian clock controls genome wide transcription of many key regulatory components in a diverse selection of vital pathways (1-3) that ultimately allow a coordination of physiological and behavioral activities and their synchronization with the environmental cycles of day and night. The analogous and homologous clock mechanisms in Drosophila and mammals are based on two interconnected feedback loops (4, 5). In Drosophila, the heterodimeric complex of transcription factors CLOCK (CLK) 3 and CYCLE (CYC) (BMAL1 in mammals) activates expression of its own inhibitors PERIOD (PER) and TIME-LESS (TIM) forming the first feedback loop. This loop is interconnected with CLK⅐CYC-mediated expression of the transcription repressor vrille (vri) and the activator par-domain protein 1 (pdp1). VRI and PDP1 control the rhythmic transcription of Clk and contribute to the robustness of molecular oscillations (6, 7). Oscillations in cyclic nucleotide, calcium, and MAPK signaling (8 -10) likely contribute to a circadian control of physiological processes such as cell proliferation (11) and the sleep/wake cycle, which is important for memory formation (12). However, these pathways also feedback on the molecular oscillator at least in part through control of CLK⅐CYC activity (13). Cross-talk between circadian and cell signaling may increase the robustness of circadian oscillations and allow a coordination of circadian transcription with physiological requirements. Previous studies showed that recruitment of the CREB-binding protein (CBP) from a limiting cellular pool mediates cross-talk between the transcription factors E2F, JAK/STAT, AP1, and nuclear hormone receptors (14 -16) that control e.g. entry into the cell cycle and the immune response. Here we show that CLK⅐CYC-...

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Section: Q7supporting

confidence: 82%

Circadian Transcription Depends on Limiting Amounts of the Transcription Co-activator nejire/CBP

Hung

Maurer

Kay

et al. 2007

Journal of Biological Chemistry

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“…One HAT shown to interact with CLK is the CBP ortholog NEJIRE (22,29). In one case NEJIRE/CBP was found to act as a transcriptional coactivator (22), but other evidence shows that overexpression of NEJIRE has a negative effect on CLK-CYC-mediated transcription (29). It is possible that the reduced levels of CLK-CYC-dependent gene expression observed after nejire overexpression are due to circadian feedback compensation and that nejire/CBP is indeed a coactivator (22).…”

mentioning

confidence: 99%

“…Another possibility is that CLK interacts with other HATs. One HAT shown to interact with CLK is the CBP ortholog NEJIRE (22,29). In one case NEJIRE/CBP was found to act as a transcriptional coactivator (22), but other evidence shows that overexpression of NEJIRE has a negative effect on CLK-CYC-mediated transcription (29).…”

mentioning

confidence: 99%

Rhythmic E-Box Binding by CLK-CYC Controls Daily Cycles in per and tim Transcription and Chromatin Modifications

Taylor

Hardin

2008

Molecular and Cellular Biology

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The Drosophila melanogaster circadian oscillator comprises interlocked per/tim and Clk transcriptional feedback loops. In the per/tim loop, CLK-CYC-dependent transcriptional activation is rhythmically repressed by PER or PER-TIM to control circadian gene expression that peaks around dusk. Here we show that rhythmic transcription of per and tim involves time-of-day-specific binding of CLK-CYC and associated cycles in chromatin modifications. Activation of per and tim transcription occurs in concert with CLK-CYC binding to upstream and/or intronic E-boxes, acetylation of histone H3-K9, and trimethylation of histone H3-K4. These events are associated with RNA polymerase II (Pol II) binding to the tim promoter and transcriptional elongation by Pol II that is constitutively bound to the per promoter. Repression of per and tim transcription is associated with PER-dependent reversal of these events. Rhythms in H3-K9 acetylation and H3-K4 trimethylation are also associated with CLOCK-BMAL1-dependent transcription in mammals, indicating that the mechanism that controls rhythmic transcription is a conserved feature of the circadian clock even though feedback repression is mediated by different proteins.

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“…Ectopic expression of Clock induces the expression of tim, and sometimes per in individual S2 cell lines (see Fig. 1) (McDonald and Rosbash 2001;Lim et al 2007). …”

Section: S2 Cells and Nuclear Translocation Of Per And Timmentioning

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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Functional Role of CREB-Binding Protein in the Circadian Clock System of Drosophila melanogaster

Cited by 52 publications

References 61 publications

Circadian Transcription Depends on Limiting Amounts of the Transcription Co-activator nejire/CBP

Circadian Transcription Depends on Limiting Amounts of the Transcription Co-activator nejire/CBP

Rhythmic E-Box Binding by CLK-CYC Controls Daily Cycles in per and tim Transcription and Chromatin Modifications

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

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