[1]杨喜艳,周天寿.一个多ON基因系统的表达动力学分析[J].江西师范大学学报(自然科学版),2016,40(01):5-14.
 YANG Xiyan,ZHOU Tianshou.The Analysis of Expression Dynamics in a Multi-On Gene System[J].Journal of Jiangxi Normal University:Natural Science Edition,2016,40(01):5-14.
点击复制

一个多ON基因系统的表达动力学分析()
分享到:

《江西师范大学学报》(自然科学版)[ISSN:1006-6977/CN:61-1281/TN]

卷:
40
期数:
2016年01期
页码:
5-14
栏目:
出版日期:
2016-01-25

文章信息/Info

Title:
The Analysis of Expression Dynamics in a Multi-On Gene System
作者:
杨喜艳;周天寿
1.广东金融学院应用数学系,广东 广州 510521; 2.中山大学数学与计算科学学院,广东 广州 510275
Author(s):
YANG Xiyan ZHOU Tianshou
1.Department of Applied Mathematics,Guangdong University of Finance,Guangzhou Guangdong 510521,China; 2.School of Mathematics and Computational Science,Sun Yat-Sen University,Guangzhou Guangdong 510275,China
关键词:
多ON基因系统 总作用效能 mRNA分布 表达噪声 爆发动力学
Keywords:
multi-on model total interaction efficiency mRNA distribution expression noise bursting kinetics
分类号:
O 242; Q 141; Q 332
文献标志码:
A
摘要:
研究了一个转录水平上的基因表达模型,它不仅考虑了启动子的复杂性,而且考虑了相互作用转录因子的调控效果.假定启动子区域有2个调控位点,启动子有1个失活态和2个激活态(即2个不同的转录出口),并考虑了绑定到不同调控位点的转录因子之间相互作用的3种代表性机制:招募机制,稳定机制和混合机制.理论分析和数值模拟结果显示:不同的转录出口能够导致mRNA分布峰的多样性; 3种机制下的平均表达水平和平均爆发频率都相同,但稳定机制诱导最大的表达噪声和平均爆发规模,而招募机制诱导最小的表达噪声和平均爆发规模.这些结果表明:细胞表型的产生源是复杂的,既与启动子结构有关也与调控机制有关.
Abstract:
The relationship between cellular phenotype across a genetically identical population and gene expression difference has being a very active topic.Here,a gene expression model at the transcription level is studied,considering not only complexity of promoter structure but also interactive effect between transcription factors.The promoter region is assumed to contain two regulatory sites and the promoter has one inactive state and two active states(i.e.,two different transcription exits).In addition,based on interaction between transcription factors binding to the different regulatory sites,three representative mechanisms are considered,including recruitment mechanism,stabilization mechanism and mixture mechanism.Theoretical analysis and numerical simulation results show that different transcription exits can lead to mRNA distribution peaks of different modes; the mRNA mean level and mean burst frequency are identical under these three mechanisms,but stabilization mechanism induces the highest expression noise and the largest mean burst size,and recruitment mechanism induces the lowest expression noise and the smallest mean burst size.These results indicate that the source of cellular phenotype is complex,which is related to both promoter structure and regulation mechanisms.

参考文献/References:

[1] Kussell E,Leibler S.Phenotypic diversity,population growth and information in fluctuating environments [J].Science,2005,309(5743):2075-2078.
[2] Acar M,Mettetal J T,van Oudenaarden A.Stochastic switching as a survival strategy in fluctuating environments [J].Nat Genet,2008,40(4):471-475.
[3] Fraser D,Kærn M.A chance at survival:gene expression noise and phenotypic diversification strategies [J].Mol Microbiol,2009,71(6):1333-1340.
[4] Lehner B.Selection to minimise noise in living systems and its implications for the evolution of gene expression [J].Mol Sys Biol,2008,4(1):170.
[5] Hung M,Chang E,Hussein R,et al.Modulating the frequency and bias of stochastic switching to control phenotypic variation [J].Nat Commun,2014,5:4574.
[6] Eldar A,Elowitz M B.Functional roles for noise in genetic circuits [J].Nature,2010,467(7312):167-173.
[7] Kærn M,Elston T C,Blake W J,et al.Stochasticity in gene expression:from theories to phenotypes [J].Nat Rev Gen,2005,6(6):451-464.
[8] Raj A,Peskin C S,Tranchina D,et al.Stochastic mRNA synthesis in mammalian cells [J].PloS Biol,2006,4(10):1707-1719.
[9] Spiller D G,Wood C D,Rand D A,et al.Measurement of single-cell dynamics [J].Nature,2010,465(7299):736-745.
[10] Sanchez A,Choubey S,Kondev J.Noise and robustness in prokaryotic regulatory networks [J].Annu Rev Microbiol,2010,64(64):257-275.
[11] Cai Long,Friedman N,Xie X Sunney.Stochastic protein expression in individual cells at the single molecule level [J].Nature,2006,440(7082):358-362.
[12] Suter D M,Molina N,Gatfield D,et al.Mammalian genes are transcribed with widely different bursting kinetics [J].Science,2011,332(6028):472-474.
[13] Larson D R,Zenklusen D,Wu Bin,et al.Real-time observation of transcription i[J]nitiation and elongation on an endogenous yeast gene [J].Science,2011,332(6028):475-478.
[14] Yunger S,Rosenfeld L,Garini Y,et al.Single-allele analysis of transcription kinetics in living mammalian cells [J].Nat Methods,2010,7(8):631-633.
[15] Ko M S H.A stochastic model for gene induction [J].J Theor Biol,1991,153(2):181-194.
[16] Kepler T B,Elston T C.Stochasticity in transcriptional regulation:origins,consequences,and mathematical representations [J].Biophys J,2001,81(6):3116-3136.
[17] Paulsson J.Models of stochastic gene expression [J].Phys Life Rev,2005,2(2):157-175.
[18] Zhang Jiajun,Chen Luonan,Zhou Tianshou.Analytical distribution and tunability of noise in a model of promoter progress [J].Biophys J,2012,102(6):1247-1257.
[19] Zhang Jiajun,Nie Qing,He Miao,et al.An effective method for computing the noise in biochemical networks [J].J Chem Phys,2013,138(8):1843-1852.
[20] Zhang Jiajun,Zhou Tianshou.Promoter-mediated transcriptional dynamics [J].Biophys J,2014,106(2):479-488.
[21] Huang Lifang,Yuan Zhanjiang,Liu Peijiang,et al.Feedback-induced counterintuitive correlations of gene expression noise with bursting kinetics [J].Phys Rev E,2014,90(5):052702.
[22] Liu Peijiang,Yuan Zhanjiang,Huang Lifang,et al.Roles of factorial noise in inducing bimodal gene expression [J].Phys Rev E,2015,91(6):062706.
[23] Saiz L,Vilar J M G.Stochastic dynamics of macromolecular-assembly networks [J].Mol Syst Biol,2006,2(1):2006.0028.
[24] Ptashne M.A genetic switch:gene control and phage lambda [M].New York:Cold Spring Harbor Laboratory Press,2004.
[25] Joung J K,Koepp D M,Hochschild A.Synergistic activation of transcription by bacteriophage-lambda cI-protein and E.coli cAMP receptor protein [J].Science,1994,265(5180):1863-1866.
[26] Bintu L,Buchler N E,Garcia H G,et al.Transcriptional regulation by the numbers:applications [J].Curr Opin Genet Dev,2005,15(2):125-135.
[27] Ochab-Marcinek A,Tabaka M.Bimodal gene expression in noncooperative regulatory systems [J].Proc Natl Acad Sci USA,2010,107(51):22096-22101.
[28] Becskei A,Serrano L.Engineering stability in gene networks by autoregulation [J].Nature,2000,405(6786):590-593.
[29] Zhang Jiajun,Yuan Zhanjiang,Zhou Tianshou.Physical limits of feedback noise-suppression in biological networks [J].Phys Biol,2009,6(4):1100-1106.
[30] Carey L B,van Dijk D,Sloot P M A,et al.Promoter sequence determines the relationship between expression level and noise [J].PloS Biol,2013,11(4):e1001528.
[31] Stekel D J,Jenkins D J.Strong negative self regulation of prokaryotic transcription factors increases the intrinsic noise of protein expression [J].Bmc Syst Biol,2008,2(2):147-154.
[32] Paulsson J.Summing up the noise in gene networks [J].Nature,2004,427(6973):415-418.
[33] Friedman N,Cai Long,Xie X Sunny.Linking stochastic dynamics to population distribution:an analytical framework of gene expression [J].Phys Rev Lett,2006,97(16):168302.
[34] Dar R D,Razooky B S,Singh A,et al.Transcriptional burst frequency and burst size are equally modulated across the human genome [J].Proc Natl Acad Sci USA,2012,109(43):17454-17459.
[35] Blake W J,Balázsi G,Kohanski M A,et al.Phenotypic consequences of promoter-mediated transcriptional noise [J].Mol Cell,2006,24(6):853-865.
[36] Dellarole M,Sánchez I E,de Prat Gay G.Thermodynamics of cooperative DNA recognition at a replication origin and transcription regulatory site [J].Biochemistry,2010,49(48):10277-10286.
[37] Gutierrez P S,Monteoliva D,Diambra L.Role of cooperative binding on noise expression [J].Phys Rev E,2009,80(1):1274-1287.
[38] Gutierrez P S,Monteoliva D,Diambra L.Cooperative binding of transcription factors promotes bimodal gene expression response [J].PloS One,2012,7(9):e44812.
[39] 周天寿.基因表达模型的研究进展:概率分布 [J].江西师范大学学报:自然科学版,2012,36(3):221-229.
[40] 周天寿.概率主方程的研究综述 [J].江西师范大学学报:自然科学版,2015,39(1):1-6.
[41] 雷锦誌.生化反应系统的建模与分析 [J].江西师范大学学报:自然科学版,2015,39(3):230-239.
[42] McAdams H H,Arkin A.Stochastic mechanisms in gene expression [J].Proc Natl Acad Sci USA,1997,94(3):814-819.
[43] Ozbudak E M,Thattai M,Kurtser I,et al.Regulation of noise in the expression of a single gene [J].Nat Genet,2002,31(1):69-73.
[44] Hansen A S,O'Shea E K.Promoter decoding of transcription factor dynamics involves a trade-off between noise and control of gene expression [J].Mol Sys Biol,2013,9(1):953.
[45] Gillespie D T.Exact stochastic simulation of coupled chemical reactions [J].J Chem Phys,1977,81(25):2340-2361.
[46] Wang Qianliang,Zhou Tianshou.Alternative-splicing-mediated gene expression [J].Phys Rev E,2014,89(1):390-400.
[47] Kallehauge T B,Robert M C,Bertrand E,et al.Nuclear retention prevents premature cytoplasmic appearance of mRNA [J].Mol Cell,2012,48(1):145-152.

备注/Memo

备注/Memo:
基金项目:国家自然科学基金(91230204,11005162,11475273,11526058,2014CB964703),2015年广东省教育厅青年创新人才类(2015KQNCX103)和2015年广东金融学院“创新强校工程”(高校重大科研成果培育计划类)资助项目.
更新日期/Last Update: 1900-01-01