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{{Short description|Functional clusters of genes}}
[[File:Representation of a Genetic Regulatory Circuit.png|thumb|Example of a genetic regulatory circuit for ''Drosophila melanogaster's'' ''huckebein'' ''(hkb)'' gene's effects on gap gene expression.|300x300px]]
'''Genetic regulatory circuits''' (also referred to as '''transcriptional regulatory circuits''') is a concept that evolved from the [[Operon]] Model discovered by [[François Jacob]] and [[Jacques Monod]].<ref name=":3">{{Cite journal|last1=Tajbakhsh|first1=Shahragim|last2=Cavalli|first2=Giacomo|last3=Richet|first3=Evelyne|date=August 2011|title=Integrated Gene Regulatory Circuits: Celebrating the 50th Anniversary of the Operon Model|journal=Molecular Cell|volume=43|issue=4|pages=505–514|doi=10.1016/j.molcel.2011.08.003|pmid=21855791|issn=1097-2765|doi-access=free}}</ref> <ref>{{Cite journal|last1=Kelly|first1=Daniel P.|last2=Scarpulla|first2=Richard C.|date=2004-02-15|title=Transcriptional regulatory circuits controlling mitochondrial biogenesis and function|url=http://genesdev.cshlp.org/content/18/4/357|journal=Genes & Development|language=en|volume=18|issue=4|pages=357–368|doi=10.1101/gad.1177604|issn=0890-9369|pmid=15004004|doi-access=free}}</ref><ref>{{Cite journal|last1=Jacob|first1=François|last2=Monod|first2=Jacques|date=1961-06-01|title=Genetic regulatory mechanisms in the synthesis of proteins|url=http://www.sciencedirect.com/science/article/pii/S0022283661800727|journal=Journal of Molecular Biology|language=en|volume=3|issue=3|pages=318–356|doi=10.1016/S0022-2836(61)80072-7|pmid=13718526|issn=0022-2836|url-access=subscription}}</ref> They are functional clusters of [[gene]]s that impact each other's expression through inducible [[transcription factor]]s and [[cis-regulatory element]]s.<ref name=":0">{{Cite journal|last1=Kim|first1=Harold D.|last2=Shay|first2=Tal|last3=O'Shea|first3=Erin K.|last4=Regev|first4=Aviv|date=2009-07-24|title=Transcriptional Regulatory Circuits: Predicting Numbers from Alphabets|url= |journal=Science|language=en|volume=325|issue=5939|pages=429–432|doi=10.1126/science.1171347|issn=0036-8075|pmc=2745280|pmid=19628860|bibcode=2009Sci...325..429K}}</ref><ref name=":1">{{Cite journal|last1=Bintu|first1=Lacramioara|last2=Buchler|first2=Nicolas E|last3=Garcia|first3=Hernan G|last4=Gerland|first4=Ulrich|last5=Hwa|first5=Terence|last6=Kondev|first6=Jané|last7=Kuhlman|first7=Thomas|last8=Phillips|first8=Rob|date=2005-04-01|title=Transcriptional regulation by the numbers: applications|url= |journal=Current Opinion in Genetics & Development|series=Chromosomes and expression mechanisms|language=en|volume=15|issue=2|pages=125–135|doi=10.1016/j.gde.2005.02.006|issn=0959-437X|pmc=3462814|pmid=15797195}}</ref>

Genetic regulatory circuits are analogous in many ways to [[electronic circuits]] in how they use signal inputs and outputs to determine [[Regulation of gene expression|gene regulation]].<ref name=":0" /><ref name=":1"/> Like electronic circuits, their organization determines their efficiency, and this has been demonstrated in circuits working in series to have a greater sensitivity of gene regulation.<ref name=":0" /><ref>{{Cite journal|last1=Hooshangi|first1=Sara|last2=Thiberge|first2=Stephan|last3=Weiss|first3=Ron|date=2005-03-08|title=Ultrasensitivity and noise propagation in a synthetic transcriptional cascade|journal=Proceedings of the National Academy of Sciences|language=en|volume=102|issue=10|pages=3581–3586|doi=10.1073/pnas.0408507102|issn=0027-8424|pmc=552778|pmid=15738412|bibcode=2005PNAS..102.3581H|doi-access=free }}</ref> They also use inputs such as trans and cis sequence regulators of genes, and outputs such as [[gene expression]] level.<ref name=":0" /><ref name=":1" /> Depending on the type of circuit, they respond constantly to outside signals, such as sugars and hormone levels, that determine how the circuit will return to its fixed point or periodic equilibrium state.<ref name=":4">{{Cite journal|last1=Payne|first1=Joshua L.|last2=Wagner|first2=Andreas|date=2015-08-20|title=Function does not follow form in gene regulatory circuits|url= |journal=Scientific Reports|language=en|volume=5|issue=1|article-number=13015|doi=10.1038/srep13015|issn=2045-2322|pmc=4542331|pmid=26290154|bibcode=2015NatSR...513015P}}</ref> Genetic regulatory circuits also have an ability to be evolutionarily rewired without the loss of the original transcriptional output level.<ref name=":2">{{Cite journal|last1=Dalal|first1=Chiraj K.|last2=Johnson|first2=Alexander D.|date=2017-07-15|title=How transcription circuits explore alternative architectures while maintaining overall circuit output|url=http://genesdev.cshlp.org/content/31/14/1397|journal=Genes & Development|language=en|volume=31|issue=14|pages=1397–1405|doi=10.1101/gad.303362.117|issn=0890-9369|pmc=5588923|pmid=28860157}}</ref><ref>{{Cite journal|last1=Hare|first1=Emily E.|last2=Peterson|first2=Brant K.|last3=Iyer|first3=Venky N.|last4=Meier|first4=Rudolf|last5=Eisen|first5=Michael B.|date=2008-06-27|title=Sepsid even-skipped Enhancers Are Functionally Conserved in Drosophila Despite Lack of Sequence Conservation|journal=PLOS Genetics|language=en|volume=4|issue=6|article-number=e1000106|doi=10.1371/journal.pgen.1000106|issn=1553-7404|pmc=2430619|pmid=18584029 |doi-access=free }}</ref> This rewiring is defined by the change in regulatory-target gene interactions, while there is still conservation of regulatory factors and target genes.<ref name=":2" /><ref>{{Cite journal|last1=Martchenko|first1=Mikhail|last2=Levitin|first2=Anastasia|last3=Hogues|first3=Herve|last4=Nantel|first4=Andre|last5=Whiteway|first5=Malcolm|date=June 2007|title=Transcriptional Rewiring of Fungal Galactose-Metabolism Circuitry|url= |journal=Current Biology|volume=17|issue=12|pages=1007–1013|doi=10.1016/j.cub.2007.05.017|issn=0960-9822|pmc=3842258|pmid=17540568|bibcode=2007CBio...17.1007M }}</ref>

== In-silico application ==
These circuits can be modelled [[in silico]] to predict the dynamics of a genetic system.<ref name=":2" /><ref>{{Cite journal|last1=Ciliberti|first1=Stefano|last2=Martin|first2=Olivier C.|last3=Wagner|first3=Andreas|date=2007-02-02|title=Robustness Can Evolve Gradually in Complex Regulatory Gene Networks with Varying Topology|journal=PLOS Computational Biology|language=en|volume=3|issue=2|article-number=e15|doi=10.1371/journal.pcbi.0030015|issn=1553-7358|pmc=1794322|pmid=17274682|bibcode=2007PLSCB...3...15C |doi-access=free }}</ref> Having constructed a [[computational model]] of the natural circuit of interest, one can use the model to make testable predictions about circuit performance.<ref name=":5">{{Citation|last1=Porter|first1=Joshua R.|title=Using Computational Modeling and Experimental Synthetic Perturbations to Probe Biological Circuits|date=2015|url= |work=Computational Methods in Synthetic Biology|pages=259–276|editor-last=Marchisio|editor-first=Mario Andrea|series=Methods in Molecular Biology|place=New York, NY|publisher=Springer|language=en|doi=10.1007/978-1-4939-1878-2_12|isbn=978-1-4939-1878-2|pmc=6311997|pmid=25487101|last2=Batchelor|first2=Eric|volume=1244}}</ref><ref>{{Cite journal|last1=Toettcher|first1=J. E.|last2=Mock|first2=C.|last3=Batchelor|first3=E.|last4=Loewer|first4=A.|last5=Lahav|first5=G.|date=2010-09-28|title=A synthetic-natural hybrid oscillator in human cells|journal=Proceedings of the National Academy of Sciences|language=en|volume=107|issue=39|pages=17047–17052|doi=10.1073/pnas.1005615107|issn=0027-8424|pmc=2947868|pmid=20837528|bibcode=2010PNAS..10717047T|doi-access=free }}</ref> When designing a synthetic circuit for a specific engineering task, a model is useful for identifying necessary connections and parameter operating regimes that give rise to a desired functional output. Similarly, when studying a natural circuit, one can use the model to identify the parts or parameter values necessary for a desired biological outcome.<ref name=":5" /><ref name=":6">{{Cite journal|last1=Elowitz|first1=Michael B.|last2=Leibler|first2=Stanislas|date=January 2000|title=A synthetic oscillatory network of transcriptional regulators|url=http://www.nature.com/articles/35002125|journal=Nature|language=en|volume=403|issue=6767|pages=335–338|doi=10.1038/35002125|pmid=10659856|bibcode=2000Natur.403..335E|s2cid=41632754|issn=0028-0836|url-access=subscription}}</ref> In other words, computational modelling and experimental synthetic perturbations can be used to probe biological circuits.<ref name=":5" /><ref name=":6" /> However, the structure of the circuits have shown to not be a reliable indicator of the function that the regulatory circuit provides for the larger cellular regulatory network.<ref name=":4" />

== Engineering and synthetic biology ==
Understanding of genetic regulatory circuits are key in the field of [[synthetic biology]], where disparate genetic elements are combined to produce novel [[biological function]]s.<ref name=":3" /><ref name=":5" /> These biological gene circuits can be used synthetically to act as physical models for studying regulatory function.<ref>{{Cite journal|last1=Bashor|first1=Caleb J.|last2=Collins|first2=James J.|date=2018-05-20|title=Understanding Biological Regulation Through Synthetic Biology|url=https://www.annualreviews.org/doi/10.1146/annurev-biophys-070816-033903|journal=Annual Review of Biophysics|volume=47|issue=1|pages=399–423|doi=10.1146/annurev-biophys-070816-033903|pmid=29547341|issn=1936-122X|hdl=1721.1/119222|s2cid=3888755 |hdl-access=free}}</ref><ref>{{Cite journal|last1=Jones|first1=Daniel L.|last2=Brewster|first2=Robert C.|last3=Phillips|first3=Rob|date=2014-12-19|title=Promoter architecture dictates cell-to-cell variability in gene expression|url= |journal=Science|language=en|volume=346|issue=6216|pages=1533–1536|doi=10.1126/science.1255301|issn=0036-8075|pmc=4388425|pmid=25525251|bibcode=2014Sci...346.1533J}}</ref>

By engineering genetic regulatory circuits, cells can be modified to take information from their environment, such as nutrient availability and developmental signals, and react in accordance to changes in their surroundings<ref>{{Cite book|last=Myers|first=Chris|title=Engineering Genetic Circuits|publisher=CRC Press|year=2018|isbn=978-0-429-19305-7|location=New York|page=39}}</ref><ref name=":7">{{Cite journal|last1=Kassaw|first1=Tessema K.|last2=Donayre-Torres|first2=Alberto J.|last3=Antunes|first3=Mauricio S.|last4=Morey|first4=Kevin J.|last5=Medford|first5=June I.|date=2018-08-01|title=Engineering synthetic regulatory circuits in plants|journal=Plant Science|series=Synthetic Biology Meets Plant Metabolism|language=en|volume=273|pages=13–22|doi=10.1016/j.plantsci.2018.04.005|pmid=29907304|s2cid=49222385 |issn=0168-9452|doi-access=free|bibcode=2018PlnSc.273...13K }}</ref> .<ref>{{Cite journal|last1=Yokobayashi|first1=Y.|last2=Weiss|first2=R.|last3=Arnold|first3=F. H.|date=2002-12-24|title=Directed evolution of a genetic circuit|journal=Proceedings of the National Academy of Sciences|language=en|volume=99|issue=26|pages=16587–16591|doi=10.1073/pnas.252535999|issn=0027-8424|pmc=139187|pmid=12451174|doi-access=free }}</ref><ref>{{Cite journal|last1=Sprinzak|first1=David|last2=Elowitz|first2=Michael B.|date=2005-11-24|title=Reconstruction of genetic circuits|url=http://www.nature.com/articles/nature04335|journal=Nature|language=en|volume=438|issue=7067|pages=443–448|doi=10.1038/nature04335|pmid=16306982|bibcode=2005Natur.438..443S|s2cid=11916084|issn=0028-0836|url-access=subscription}}</ref> In plant synthetic biology, genetic regulatory circuits can be used to program traits to increase crop plant efficiency by increasing their robustness to environmental stressors.<ref name=":7" /><ref name=":8">{{Cite journal|last1=Julve Parreño|first1=Jose Manuel|last2=Huet|first2=Estefanía|last3=Fernández-del-Carmen|first3=Asun|last4=Segura|first4=Alvaro|last5=Venturi|first5=Micol|last6=Gandía|first6=Antoni|last7=Pan|first7=Wei-song|last8=Albaladejo|first8=Irene|last9=Forment|first9=Javier|last10=Pla|first10=Davinia|last11=Wigdorovitz|first11=Andrés|date=March 2018|title=A synthetic biology approach for consistent production of plant-made recombinant polyclonal antibodies against snake venom toxins|url= |journal=Plant Biotechnology Journal|language=en|volume=16|issue=3|pages=727–736|doi=10.1111/pbi.12823|pmc=5814581|pmid=28850773 |bibcode=2018PBioJ..16..727J }}</ref> Additionally, they are used to produce [[biopharmaceutical]]s for medical intervention.<ref name=":7" /><ref name=":8" />

== References ==
{{Reflist}}

[[Category:Genetics]]
[[Category:Gene expression]]
[[Category:Systems biology]]

Gene regulatory circuit - История изменений

Admin: 1 версия импортирована

ru>Citation bot: Added bibcode. | Use this bot. Report bugs. | Suggested by Abductive | Category:Gene expression | #UCB_Category 123/400