Stimulus-induced modulation of transcriptional bursting in a single mammalian gene

被引：112
作者：
Molina, Nacho [1 ]
Suter, David M. [2 ]
Cannavo, Rosamaria [1 ]
Zoller, Benjamin [1 ]
Gotic, Ivana [2 ]
Naef, Felix [1 ]
机构：
[1] Ecole Polytech Fed Lausanne, Swiss Inst Bioinformat, Sch Life Sci, Inst Bioengn, CH-1015 Lausanne, Switzerland
[2] Univ Geneva, Natl Ctr Competence Res Frontiers Genet, Dept Mol Biol, CH-1211 Geneva, Switzerland
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2013年 / 110卷 / 51期
基金：
瑞士国家科学基金会; 欧洲研究理事会;
关键词：
stochastic gene expression; single-cell dynamics; computational modeling; SERUM RESPONSE FACTOR; ANGIOGENESIS IN-VIVO; GLUCOCORTICOID-RECEPTOR; DIGITAL ACTIVATION; LIVING CELLS; DYNAMICS; EXPRESSION; RNA; MIGRATION; YEAST;
D O I：
10.1073/pnas.1312310110
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Mammalian genes are often transcribed discontinuously as short bursts of RNA synthesis followed by longer silent periods. However, how these "on" and "off" transitions, together with the burst sizes, are modulated in single cells to increase gene expression upon stimulation is poorly characterized. By combining single-cell time-lapse luminescence imaging with stochastic modeling of the time traces, we quantified the transcriptional responses of the endogenous connective tissue growth factor gene to different physiological stimuli: serum and TGF-beta 1. Both stimuli caused a rapid and acute increase in burst sizes. Whereas TGF-beta 1 showed prolonged transcriptional activation mediated by an increase of transcription rate, serum stimulation resulted in a large and temporally tight first transcriptional burst, followed by a refractory period in the range of hours. Our study thus reveals how different physiological stimuli can trigger kinetically distinct transcriptional responses of the same gene.
引用
收藏
页码：20563 / 20568
页数：6
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