Phenotypic consequences of promoter-mediated transcriptional noise

被引:465
作者
Blake, William J.
Balazsi, Gbor
Kohanski, Michael A.
Isaacs, Farren J.
Murphy, Kevin F.
Kuang, Yina
Cantor, Charles R.
Walt, David R.
Collins, James J. [1 ]
机构
[1] Boston Univ, Dept Biomed Engn, Boston, MA 02215 USA
[2] Boston Univ, Ctr BioDynam, Boston, MA 02215 USA
[3] Boston Univ, Ctr Adv Biotechnol, Boston, MA 02215 USA
[4] Boston Univ, Dept Biol, Boston, MA 02215 USA
[5] Boston Univ, Sch Med, Boston, MA 02118 USA
[6] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA
[7] Tufts Univ, Dept Chem, Medford, MA 02155 USA
基金
美国国家卫生研究院; 美国国家科学基金会;
关键词
D O I
10.1016/j.molcel.2006.11.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A more complete understanding of the causes and effects of cell-cell variability in gene expression is needed to elucidate whether the resulting phenotypes are disadvantageous or confer some adaptive advantage. Here we show that increased variability in gene expression, affected by the sequence of the TATA box, can be beneficial after an acute change in environmental conditions. We rationally introduce mutations within the TATA region of an engineered Saccharomyces cerevisiae GAL1 promoter and measure promoter responses that can be characterized as being either highly variable and rapid or steady and slow. We computationally illustrate how a stable transcription scaffold can result in "bursts" of gene expression, enabling rapid individual cell responses in the transient and increased cell-cell variability at steady state. We experimentally verify computational predictions that the rapid response and increased cell-cell variability enabled by TATA-containing promoters confer a clear benefit in the face of an acute environmental stress.
引用
收藏
页码:853 / 865
页数:13
相关论文
共 61 条
[1]   Enhancement of cellular memory by reducing stochastic transitions [J].
Acar, M ;
Becskei, A ;
van Oudenaarden, A .
NATURE, 2005, 435 (7039) :228-232
[2]  
Ausubel FM, 1995, SHORT PROTOCOLS MOL
[3]   Signals for TBP/TATA box recognition [J].
Bareket-Samish, A ;
Cohen, I ;
Haran, TE .
JOURNAL OF MOLECULAR BIOLOGY, 2000, 299 (04) :965-977
[4]   Identification and distinct regulation of yeast TATA box-containing genes [J].
Basehoar, AD ;
Zanton, SJ ;
Pugh, BF .
CELL, 2004, 116 (05) :699-709
[5]   Engineering stability in gene networks by autoregulation [J].
Becskei, A ;
Serrano, L .
NATURE, 2000, 405 (6786) :590-593
[6]   Contributions of low molecule number and chromosomal positioning to stochastic gene expression [J].
Becskei, A ;
Kaufmann, BB ;
van Oudenaarden, A .
NATURE GENETICS, 2005, 37 (09) :937-944
[7]   Positive feedback in eukaryotic gene networks:: cell differentiation by graded to binary response conversion [J].
Becskei, A ;
Séraphin, B ;
Serrano, L .
EMBO JOURNAL, 2001, 20 (10) :2528-2535
[8]  
BERDY J, 1980, AMINO ACID PEPTIDE A, P495
[9]   Noise in eukaryotic gene expression [J].
Blake, WJ ;
Kærn, M ;
Cantor, CR ;
Collins, JJ .
NATURE, 2003, 422 (6932) :633-637
[10]   Independent recruitment in vivo by Gal4 of two complexes required for transcription [J].
Bryant, GO ;
Ptashne, M .
MOLECULAR CELL, 2003, 11 (05) :1301-1309