Pre-dispositions and epigenetic inheritance in the Escherichia coli lactose operon bistable switch.
The lactose operon regulation in Escherichia coli is a primary model of phenotypic switching, reminiscent of cell fate determination in higher organisms. Under conditions of bistability, an isogenic cell population partitions into two subpopulations, with the operon's genes turned on or remaining off. It is generally hypothesized that the final state of a cell depends solely on stochastic fluctuations of the network's protein concentrations, particularly on bursts of lactose permease expression. Nevertheless, the mechanisms underlying the cell switching decision are not fully understood. We designed a microfluidic system to follow the formation of a transiently bimodal population within growing microcolonies. The analysis of genealogy and cell history revealed the existence of pre-disposing factors for switching that are epigenetically inherited. Both the pre-induction expression stochasticity of the lactose operon repressor LacI and the cellular growth rate are predictive factors of the cell's response upon induction, with low LacI concentration and slow growth correlating with higher switching probability. Thus, stochasticity at the local level of the network and global physiology are synergistically involved in cell response determination.
Robert
Lydia
L
INSERM, and Faculty of Medicine, Paris Descartes University, 24 Rue de Faubourg St Jacques, Paris, France.
Paul
Gregory
G
Chen
Yong
Y
Taddei
François
F
Baigl
Damien
D
Lindner
Ariel B
AB
D044127:Epigenesis, Genetic; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development; D007763:Lac Operon; D046210:Microfluidic Analytical Techniques; D008856:Microscopy, Fluorescence; D013269:Stochastic Processes; D049490:Systems Biology / Q000379:methods*
PLoS One. 2006 Dec 20;1:e49
17183678
Science. 2008 Dec 5;322(5907):1511-6
19023046
Mol Microbiol. 2006 Aug;61(3):564-72
16879639
Proc Natl Acad Sci U S A. 1957 Jul 15;43(7):553-66
16590055
PLoS Biol. 2007 Sep;5(9):e239
17803359
Phys Biol. 2008 Nov 07;5(4):046001
18997273
Nature. 2004 Feb 19;427(6976):737-40
14973486
EMBO J. 2001 May 15;20(10):2528-35
11350942
Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4393-8
18326026
Science. 2002 Aug 16;297(5584):1183-6
12183631
J Cell Biol. 2003 May 12;161(3):471-6
12743100
Science. 2007 Jul 27;317(5837):526-9
17569828
Cell. 2008 Oct 17;135(2):216-26
18957198
Science. 2008 Oct 17;322(5900):442-6
18927393
Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20245-50
19073937
Nature. 2005 Jul 28;436(7050):588-92
16049495
Cold Spring Harb Symp Quant Biol. 1961;26:389-401
14475415
Proc Natl Acad Sci U S A. 2008 Feb 26;105(8):3076-81
18287048
PLoS Biol. 2009 Feb 24;7(2):e44
19243224
Science. 2004 May 14;304(5673):983-7
15087506
Science. 2008 Apr 4;320(5872):65-8
18388284
PLoS Comput Biol. 2007 Jun;3(6):e111
17590077
Genetics. 2004 May;167(1):523-30
15166174
Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12449-54
16099833
J Theor Biol. 1999 Nov 7;201(1):25-36
10534433
Annu Rev Biochem. 1984;53:75-117
6206783
Nature. 2000 Jun 1;405(6786):590-3
10850721
Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20705-10
19098103
Science. 2005 Sep 23;309(5743):2075-8
16123265
Nucleic Acids Res. 1997 Mar 15;25(6):1203-10
9092630
PLoS Biol. 2005 Feb;3(2):e45
15685293