Gene regulatory circuit

Example of a genetic regulatory circuit for Drosophila melanogaster's huckebein (hkb) gene's effects on gap gene expression.

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.[1] [2][3] They are functional clusters of genes that impact each other's expression through inducible transcription factors and cis-regulatory elements.[4][5]

Genetic regulatory circuits are analogous in many ways to electronic circuits in how they use signal inputs and outputs to determine gene regulation.[4][5] 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.[4][6] They also use inputs such as trans and cis sequence regulators of genes, and outputs such as gene expression level.[4][5] 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.[7] Genetic regulatory circuits also have an ability to be evolutionarily rewired without the loss of the original transcriptional output level.[8][9] This rewiring is defined by the change in regulatory-target gene interactions, while there is still conservation of regulatory factors and target genes.[8][10]

  1. ^ Tajbakhsh, Shahragim; Cavalli, Giacomo; Richet, Evelyne (August 2011). "Integrated Gene Regulatory Circuits: Celebrating the 50th Anniversary of the Operon Model". Molecular Cell. 43 (4): 505–514. doi:10.1016/j.molcel.2011.08.003. ISSN 1097-2765. PMID 21855791.
  2. ^ Kelly, Daniel P.; Scarpulla, Richard C. (2004-02-15). "Transcriptional regulatory circuits controlling mitochondrial biogenesis and function". Genes & Development. 18 (4): 357–368. doi:10.1101/gad.1177604. ISSN 0890-9369. PMID 15004004.
  3. ^ Jacob, François; Monod, Jacques (1961-06-01). "Genetic regulatory mechanisms in the synthesis of proteins". Journal of Molecular Biology. 3 (3): 318–356. doi:10.1016/S0022-2836(61)80072-7. ISSN 0022-2836. PMID 13718526.
  4. ^ a b c d Kim, Harold D.; Shay, Tal; O’Shea, Erin K.; Regev, Aviv (2009-07-24). "Transcriptional Regulatory Circuits: Predicting Numbers from Alphabets". Science. 325 (5939): 429–432. Bibcode:2009Sci...325..429K. doi:10.1126/science.1171347. ISSN 0036-8075. PMC 2745280. PMID 19628860.
  5. ^ a b c Bintu, Lacramioara; Buchler, Nicolas E; Garcia, Hernan G; Gerland, Ulrich; Hwa, Terence; Kondev, Jané; Kuhlman, Thomas; Phillips, Rob (2005-04-01). "Transcriptional regulation by the numbers: applications". Current Opinion in Genetics & Development. Chromosomes and expression mechanisms. 15 (2): 125–135. doi:10.1016/j.gde.2005.02.006. ISSN 0959-437X. PMC 3462814. PMID 15797195.
  6. ^ Hooshangi, Sara; Thiberge, Stephan; Weiss, Ron (2005-03-08). "Ultrasensitivity and noise propagation in a synthetic transcriptional cascade". Proceedings of the National Academy of Sciences. 102 (10): 3581–3586. Bibcode:2005PNAS..102.3581H. doi:10.1073/pnas.0408507102. ISSN 0027-8424. PMC 552778. PMID 15738412.
  7. ^ Payne, Joshua L.; Wagner, Andreas (2015-08-20). "Function does not follow form in gene regulatory circuits". Scientific Reports. 5 (1): 13015. Bibcode:2015NatSR...513015P. doi:10.1038/srep13015. ISSN 2045-2322. PMC 4542331. PMID 26290154.
  8. ^ a b Dalal, Chiraj K.; Johnson, Alexander D. (2017-07-15). "How transcription circuits explore alternative architectures while maintaining overall circuit output". Genes & Development. 31 (14): 1397–1405. doi:10.1101/gad.303362.117. ISSN 0890-9369. PMC 5588923. PMID 28860157.
  9. ^ Hare, Emily E.; Peterson, Brant K.; Iyer, Venky N.; Meier, Rudolf; Eisen, Michael B. (2008-06-27). "Sepsid even-skipped Enhancers Are Functionally Conserved in Drosophila Despite Lack of Sequence Conservation". PLOS Genetics. 4 (6): e1000106. doi:10.1371/journal.pgen.1000106. ISSN 1553-7404. PMC 2430619. PMID 18584029.
  10. ^ Martchenko, Mikhail; Levitin, Anastasia; Hogues, Herve; Nantel, Andre; Whiteway, Malcolm (June 2007). "Transcriptional Rewiring of Fungal Galactose-Metabolism Circuitry". Current Biology. 17 (12): 1007–1013. Bibcode:2007CBio...17.1007M. doi:10.1016/j.cub.2007.05.017. ISSN 0960-9822. PMC 3842258. PMID 17540568.