dorsal/arxiv
View SchemaStochastic model of transcription factor-regulated gene expression
| Authors | Rajesh Karmakar, Indrani Bose |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0602006 |
| URL | https://arxiv.org/abs/q-bio/0602006 |
| DOI | 10.1088/1478-3975/3/3/005 |
Abstract
We consider a stochastic model of transcription factor (TF)-regulated gene expression. The model describes two genes: Gene A and Gene B which synthesize the TFs and the target gene proteins respectively. We show through analytic calculations that the TF fluctuations have a significant effect on the distribution of the target gene protein levels when the mean TF level falls in the highest sensitive region of the dose-response curve. We further study the effect of reducing the copy number of Gene A from two to one. The enhanced TF fluctuations yield results different from those in the deterministic case. The probability that the target gene protein level exceeds a threshold value is calculated with a knowledge of the probability density functions associated with the TF and target gene protein levels. Numerical simulation results for a more detailed stochastic model are shown to be in agreement with those obtained through analytic calculations. The relevance of these results in the context of the genetic disorder haploinsufficiency is pointed out. Some experimental observations on the haploinsufficiency of the tumour suppressor gene, Nkx3.1, are explained with the help of the stochastic model of TF-regulated gene expression.
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"abstract": "We consider a stochastic model of transcription factor (TF)-regulated gene\nexpression. The model describes two genes: Gene A and Gene B which synthesize\nthe TFs and the target gene proteins respectively. We show through analytic\ncalculations that the TF fluctuations have a significant effect on the\ndistribution of the target gene protein levels when the mean TF level falls in\nthe highest sensitive region of the dose-response curve. We further study the\neffect of reducing the copy number of Gene A from two to one. The enhanced TF\nfluctuations yield results different from those in the deterministic case. The\nprobability that the target gene protein level exceeds a threshold value is\ncalculated with a knowledge of the probability density functions associated\nwith the TF and target gene protein levels. Numerical simulation results for a\nmore detailed stochastic model are shown to be in agreement with those obtained\nthrough analytic calculations. The relevance of these results in the context of\nthe genetic disorder haploinsufficiency is pointed out. Some experimental\nobservations on the haploinsufficiency of the tumour suppressor gene, Nkx3.1,\nare explained with the help of the stochastic model of TF-regulated gene\nexpression.",
"arxiv_id": "q-bio/0602006",
"authors": [
"Rajesh Karmakar",
"Indrani Bose"
],
"categories": [
"q-bio.QM",
"cond-mat.stat-mech"
],
"doi": "10.1088/1478-3975/3/3/005",
"title": "Stochastic model of transcription factor-regulated gene expression",
"url": "https://arxiv.org/abs/q-bio/0602006"
},
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