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===Negative auto-regulation (NAR)===

===Negative auto-regulation (NAR)===

[[Image:Autoregulation motif.png|thumb|Schematic representation of an auto-regulation motif]]

[[Image:Autoregulation motif.png|thumb|Schematic representation of an auto-regulation motif]]

One of simplest and most abundant network motifs in ''[[Escherichia coli|E. coli]]'' is negative auto-regulation in which a transcription factor (TF) represses its own transcription. This motif was shown to perform two important functions. The first function is response acceleration. NAR was shown to speed-up the response to signals both theoretically <ref name="zab1">{{cite journal |doi=10.1016/j.jtbi.2011.06.021 |author=Zabet NR |title=Negative feedback and physical limits of genes |journal=Journal of Theoretical Biology |volume= 284|issue=1 |pages=82–91 |date=September 2011 |pmid=21723295 |arxiv=1408.1869 |citeseerx=10.1.1.759.5418 }}</ref> and experimentally. This was first shown in a synthetic transcription network<ref name="ros1">{{cite journal |doi=10.1016/S0022-2836(02)00994-4 |vauthors=Rosenfeld N, Elowitz MB, Alon U |title=Negative autoregulation speeds the response times of transcription networks |journal=J. Mol. Biol. |volume=323 |issue=5 |pages=785–93 |date=November 2002 |pmid=12417193 |citeseerx=10.1.1.126.2604 }}</ref> and later on in the natural context in the SOS DNA repair system of E .coli.<ref name="cam1">{{cite journal |vauthors=Camas FM, Blázquez J, Poyatos JF |title=Autogenous and nonautogenous control of response in a genetic network |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=103 |issue=34 |pages=12718–23 |date=August 2006 |pmid=16908855 |pmc=1568915 |doi=10.1073/pnas.0602119103 |bibcode=2006PNAS..10312718C }}</ref> The second function is increased stability of the auto-regulated gene product concentration against stochastic noise, thus reducing variations in protein levels between different cells.<ref name="bec1">{{cite journal |vauthors=Becskei A, Serrano L |title=Engineering stability in gene networks by autoregulation |journal=Nature |volume=405 |issue=6786 |pages=590–3 |date=June 2000 |pmid=10850721 |doi=10.1038/35014651}}</ref><ref name="dub1">{{cite journal |vauthors=Dublanche Y, Michalodimitrakis K, Kümmerer N, Foglierini M, Serrano L |title=Noise in transcription negative feedback loops: simulation and experimental analysis |journal=Mol. Syst. Biol. |volume=2 |pages=41 |year=2006 |pmid=16883354 |pmc=1681513 |doi=10.1038/msb4100081 |issue=1}}</ref><ref name="shi1">{{cite journal |vauthors=Shimoga V, White J, Li Y, Sontag E, Bleris L |title= Synthetic mammalian transgene negative autoregulation |journal=Mol. Syst. Biol. |volume=9 |pages=670 |year=2013|doi=10.1038/msb.2013.27|pmid= 23736683 |pmc= 3964311 }}</ref>

One of simplest and most abundant network motifs in ''[[Escherichia coli|E. coli]]'' is negative auto-regulation in which a transcription factor (TF) represses its own transcription. This motif was shown to perform two important functions. The first function is response acceleration. NAR was shown to speed-up the response to signals both theoretically <ref name="zab1">{{cite journal |doi=10.1016/j.jtbi.2011.06.021 |author=Zabet NR |title=Negative feedback and physical limits of genes |journal=Journal of Theoretical Biology |volume= 284|issue=1 |pages=82–91 |date=September 2011 |pmid=21723295 |arxiv=1408.1869 |citeseerx=10.1.1.759.5418 }}</ref> and experimentally. This was first shown in a synthetic transcription network<ref name="ros1">{{cite journal |doi=10.1016/S0022-2836(02)00994-4 |vauthors=Rosenfeld N, Elowitz MB, Alon U |title=Negative autoregulation speeds the response times of transcription networks |journal=J. Mol. Biol. |volume=323 |issue=5 |pages=785–93 |date=November 2002 |pmid=12417193 |citeseerx=10.1.1.126.2604 }}</ref> and later on in the natural context in the SOS DNA repair system of E .coli.<ref name="cam1">{{cite journal |vauthors=Camas FM, Blázquez J, Poyatos JF |title=Autogenous and nonautogenous control of response in a genetic network |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=103 |issue=34 |pages=12718–23 |date=August 2006 |pmid=16908855 |pmc=1568915 |doi=10.1073/pnas.0602119103 |bibcode=2006PNAS..10312718C }}</ref> The second function is increased stability of the auto-regulated gene product concentration against stochastic noise, thus reducing variations in protein levels between different cells.<ref name="bec1">{{cite journal |vauthors=Becskei A, Serrano L |title=Engineering stability in gene networks by autoregulation |journal=Nature |volume=405 |issue=6786 |pages=590–3 |date=June 2000 |pmid=10850721 |doi=10.1038/35014651}}</ref><ref name="dub1">{{cite journal |vauthors=Dublanche Y, Michalodimitrakis K, Kümmerer N, Foglierini M, Serrano L |title=Noise in transcription negative feedback loops: simulation and experimental analysis |journal=Mol. Syst. Biol. |volume=2 |pages=41 |year=2006 |pmid=16883354 |pmc=1681513 |doi=10.1038/msb4100081 |issue=1}}</ref><ref name="shi1">{{cite journal |vauthors=Shimoga V, White J, Li Y, Sontag E, Bleris L |title= Synthetic mammalian transgene negative autoregulation |journal=Mol. Syst. Biol. |volume=9 |pages=670 |year=2013|doi=10.1038/msb.2013.27|pmid= 23736683 |pmc= 3964311 }}</ref>