stochastic modeling for the expression of a gene regulated by competing transcription factors随机建模为一个基因的表达受转录因子竞争.pdfVIP

Stochastic Modeling for the Expression of a Gene Regulated by Competing Transcription Factors Hsih-Te Yang, Minoru S. H. Ko* Developmental Genomics and Aging Section, Laboratory of Genetics, National Institute on Aging, National Institutes of Health (NIH), Baltimore, Maryland, United States of America Abstract It is widely accepted that gene expression regulation is a stochastic event. The common approach for its computer simulation requires detailed information on the interactions of individual molecules, which is often not available for the analyses of biological experiments. As an alternative approach, we employed a more intuitive model to simulate the experimental result, the Markov-chain model, in which a gene is regulated by activators and repressors, which bind the same site in a mutually exclusive manner. Our stochastic simulation in the presence of both activators and repressors predicted a Hill-coefficient of the dose-response curve closer to the experimentally observed value than the calculated value based on the simple additive effects of activators alone and repressors alone. The simulation also reproduced the heterogeneity of gene expression levels among individual cells observed by Fluorescence Activated Cell Sorting analysis. Therefore, our approach may help to apply stochastic simulations to broader experimental data. Citation: Yang H-T, Ko MSH (2012) Stochastic Modeling for the Expression of a Gene Regulated by Competing Transcription Factors. PLoS ONE 7(3): e32376. doi:10.1371/journal.pone.0032376 Editor: Anna Tramontano, University of Rome, Italy Received August 3, 2011; Accepted January 28, 2012; Published March 14, 2012 This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or oth