Mammalian Genes Are Transcribed with Widely Different Bursting Kinetics

被引:679
作者
Suter, David M. [1 ,2 ]
Molina, Nacho [3 ,4 ]
Gatfield, David [1 ,2 ,5 ]
Schneider, Kim [1 ,2 ]
Schibler, Ueli [1 ,2 ]
Naef, Felix [3 ,4 ]
机构
[1] Univ Geneva, Dept Mol Biol, CH-1211 Geneva, Switzerland
[2] Natl Ctr Competence Res Frontiers Genet, CH-1211 Geneva, Switzerland
[3] Ecole Polytech Fed Lausanne, Sch Life Sci, Inst Bioengn, CH-1015 Lausanne, Switzerland
[4] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland
[5] Univ Lausanne, Ctr Integrat Genom, CH-1015 Lausanne, Switzerland
基金
瑞士国家科学基金会; 欧洲研究理事会;
关键词
EXPRESSION; CELLS; TIME;
D O I
10.1126/science.1198817
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
In prokaryotes and eukaryotes, most genes appear to be transcribed during short periods called transcriptional bursts, interspersed by silent intervals. We describe how such bursts generate gene-specific temporal patterns of messenger RNA (mRNA) synthesis in mammalian cells. To monitor transcription at high temporal resolution, we established various gene trap cell lines and transgenic cell lines expressing a short-lived luciferase protein from an unstable mRNA, and recorded bioluminescence in real time in single cells. Mathematical modeling identified gene-specific on-and off-switching rates in transcriptional activity and mean numbers of mRNAs produced during the bursts. Transcriptional kinetics were markedly altered by cis-regulatory DNA elements. Our analysis demonstrated that bursting kinetics are highly gene-specific, reflecting refractory periods during which genes stay inactive for a certain time before switching on again.
引用
收藏
页码:472 / 474
页数:3
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