dorsal/arxiv
View SchemaSimulation of Drosophila Circadian Oscillations, Mutations, and Light Responses by a Model with VRI, PDP-1, and CLK
| Authors | Paul Smolen, Paul E. Hardin, Brian S. Lo, Douglas A. Baxter, John H. Byrne |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0401031 |
| URL | https://arxiv.org/abs/q-bio/0401031 |
| DOI | 10.1016/S0006-3495(04)74332-5 |
Abstract
A model of Drosophila circadian rhythm generation was developed to represent feedback loops based on transcriptional regulation of per, Clk (dclock), Pdp-1, and vri (vrille). The model postulates that histone acetylation kinetics make transcriptional activation a nonlinear function of [CLK]. Such a nonlinearity is essential to simulate robust circadian oscillations of transcription in our model and in previous models. Simulations suggest two positive feedback loops involving Clk are not essential for oscillations, because oscillations of [PER] were preserved when Clk, vri, or Pdp-1 expression was fixed. Eliminating the negative feedback loop in which PER represses per expression abolished oscillations. Simulations of per or Clk null mutations and of vri, Clk, or Pdp-1 heterozygous null mutations altered model behavior in ways similar to experimental data. The model simulated a photic phase-response curve resembling experimental curves, and oscillations entrained to simulated light-dark cycles. The model makes experimental predictions, some of which could be tested in transgenic Drosophila.
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"abstract": "A model of Drosophila circadian rhythm generation was developed to represent\nfeedback loops based on transcriptional regulation of per, Clk (dclock), Pdp-1,\nand vri (vrille). The model postulates that histone acetylation kinetics make\ntranscriptional activation a nonlinear function of [CLK]. Such a nonlinearity\nis essential to simulate robust circadian oscillations of transcription in our\nmodel and in previous models. Simulations suggest two positive feedback loops\ninvolving Clk are not essential for oscillations, because oscillations of [PER]\nwere preserved when Clk, vri, or Pdp-1 expression was fixed. Eliminating the\nnegative feedback loop in which PER represses per expression abolished\noscillations. Simulations of per or Clk null mutations and of vri, Clk, or\nPdp-1 heterozygous null mutations altered model behavior in ways similar to\nexperimental data. The model simulated a photic phase-response curve resembling\nexperimental curves, and oscillations entrained to simulated light-dark cycles.\nThe model makes experimental predictions, some of which could be tested in\ntransgenic Drosophila.",
"arxiv_id": "q-bio/0401031",
"authors": [
"Paul Smolen",
"Paul E. Hardin",
"Brian S. Lo",
"Douglas A. Baxter",
"John H. Byrne"
],
"categories": [
"q-bio.MN",
"q-bio.SC"
],
"doi": "10.1016/S0006-3495(04)74332-5",
"title": "Simulation of Drosophila Circadian Oscillations, Mutations, and Light Responses by a Model with VRI, PDP-1, and CLK",
"url": "https://arxiv.org/abs/q-bio/0401031"
},
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