switch genes


Summary: Genes that cause the epigenotype (i.e., the interrelated developmental pathways through which the adult organism is realized) to switch to an alternate cell lineage-related pathway. Switch complexes control the expression of normal functional development as well as oncogenic transformation.

Top Publications

  1. Lim H, van Oudenaarden A. A multistep epigenetic switch enables the stable inheritance of DNA methylation states. Nat Genet. 2007;39:269-75 pubmed
    ..This mechanism of generating multiple states is an alternative to feedback regulation, and its general principle should be applicable to the analysis of other epigenetic switches and the design of synthetic circuits. ..
  2. Tian T, Burrage K. Bistability and switching in the lysis/lysogeny genetic regulatory network of bacteriophage lambda. J Theor Biol. 2004;227:229-37 pubmed
    ..The approach in this paper represents an attempt to describe the regulatory mechanism in genetic regulatory network under the influence of intrinsic noise in the framework of continuous models. ..
  3. Dumitru R, Navarathna D, Semighini C, Elowsky C, Dumitru R, Dignard D, et al. In vivo and in vitro anaerobic mating in Candida albicans. Eukaryot Cell. 2007;6:465-72 pubmed
    ..These cells were true mating products because they were tetraploid, mononuclear, and prototrophic, and they contained the heterologous hisG marker from one of the parental strains. ..
  4. Srikantha T, Borneman A, Daniels K, Pujol C, Wu W, Seringhaus M, et al. TOS9 regulates white-opaque switching in Candida albicans. Eukaryot Cell. 2006;5:1674-87 pubmed
    ..TOS9 has also been referred to as EAP2 and WOR1. ..
  5. Hnisz D, Schwarzm├╝ller T, Kuchler K. Transcriptional loops meet chromatin: a dual-layer network controls white-opaque switching in Candida albicans. Mol Microbiol. 2009;74:1-15 pubmed publisher
    ..Our observations postulate that chromatin modifications may serve as a means to integrate environmental or host stimuli through the underlying transcriptional circuits to determine cell fate in C. albicans. ..
  6. Zordan R, Miller M, Galgoczy D, Tuch B, Johnson A. Interlocking transcriptional feedback loops control white-opaque switching in Candida albicans. PLoS Biol. 2007;5:e256 pubmed
    ..Our observations indicate that a key role of the interlocking feedback loop network is to stably maintain each epigenetic state through many cell divisions. ..
  7. Ruhela A, Verma M, Edwards J, Bhat P, Bhartiya S, Venkatesh K. Autoregulation of regulatory proteins is key for dynamic operation of GAL switch in Saccharomyces cerevisiae. FEBS Lett. 2004;576:119-26 pubmed
    ..The dynamic model was also used to obtain insights on the preculturing effect on the system behavior. ..
  8. Zordan R, Galgoczy D, Johnson A. Epigenetic properties of white-opaque switching in Candida albicans are based on a self-sustaining transcriptional feedback loop. Proc Natl Acad Sci U S A. 2006;103:12807-12 pubmed
    ..Thus, this simple model can account for both the heritability of the white and opaque states and the stochastic nature of the switching between them. ..
  9. Ertel A, Tozeren A. Switch-like genes populate cell communication pathways and are enriched for extracellular proteins. BMC Genomics. 2008;9:3 pubmed publisher
    ..Bimodal genes comprise a candidate set of biomarkers for a large number of disease states because their expressions are tightly regulated at the transcription level. ..

More Information


  1. Warren P, ten Wolde P. Enhancement of the stability of genetic switches by overlapping upstream regulatory domains. Phys Rev Lett. 2004;92:128101 pubmed
    ..Our results suggest that robustness against biochemical noise can provide a selection pressure that drives operons together in the course of evolution. ..
  2. Huang G, Wang H, Chou S, Nie X, Chen J, Liu H. Bistable expression of WOR1, a master regulator of white-opaque switching in Candida albicans. Proc Natl Acad Sci U S A. 2006;103:12813-8 pubmed
    ..We present genetic evidence for feedback regulation of WOR1 transcription. The feedback regulation explains the bistable and stochastic nature of white-opaque switching. ..
  3. Mandal M, Breaker R. Adenine riboswitches and gene activation by disruption of a transcription terminator. Nat Struct Mol Biol. 2004;11:29-35 pubmed
  4. Miller M, Johnson A. White-opaque switching in Candida albicans is controlled by mating-type locus homeodomain proteins and allows efficient mating. Cell. 2002;110:293-302 pubmed
    ..As white cells are generally more robust in a mammalian host than are opaque cells, this strategy allows the organism to survive the rigors of life within a mammalian host, yet generate mating-competent cells. ..
  5. Corbino K, Barrick J, Lim J, Welz R, Tucker B, Puskarz I, et al. Evidence for a second class of S-adenosylmethionine riboswitches and other regulatory RNA motifs in alpha-proteobacteria. Genome Biol. 2005;6:R70 pubmed
    ..The two SAM riboswitches might be 'RNA World' relics that were selectively retained in certain bacterial lineages or new motifs that have emerged since the divergence of the major bacterial groups. ..
  6. Gatton M, Peters J, Fowler E, Cheng Q. Switching rates of Plasmodium falciparum var genes: faster than we thought?. Trends Parasitol. 2003;19:202-8 pubmed
    ..The implications of the predicted switching rates are discussed. ..
  7. Sohanpal B, Kulasekara H, Bonnen A, Blomfield I. Orientational control of fimE expression in Escherichia coli. Mol Microbiol. 2001;42:483-94 pubmed
    ..Analysis of the fim switch reveals that it contains two inhibitory elements that exert orientational control independently. ..
  8. Burns L, Peterson C. Protein complexes for remodeling chromatin. Biochim Biophys Acta. 1997;1350:159-68 pubmed
  9. Banwait S, Galvan V, Zhang J, Gorostiza O, Ataie M, Huang W, et al. C-terminal cleavage of the amyloid-beta protein precursor at Asp664: a switch associated with Alzheimer's disease. J Alzheimers Dis. 2008;13:1-16 pubmed
  10. Fenton J, Pratt G, Rawstron A, Sibley K, Rothwell D, Yates Z, et al. Genomic characterization of the chromosomal breakpoints of t(4;14) of multiple myeloma suggests more than one possible aetiological mechanism. Oncogene. 2003;22:1103-13 pubmed
  11. Zhang S, Chen L, Goff S. Regulation of gene expression by small molecules in rice. Novartis Found Symp. 2001;236:85-95; discussion 95-6 pubmed
    ..The described gene switch system represents an important tool for situations requiring conditional gene expression in a monocot species. ..
  12. Zhu X, Yin L, Hood L, Ao P. Robustness, stability and efficiency of phage lambda genetic switch: dynamical structure analysis. J Bioinform Comput Biol. 2004;2:785-817 pubmed
  13. Zeiser S, Franz U, Wittich O, Liebscher V. Simulation of genetic networks modelled by piecewise deterministic Markov processes. IET Syst Biol. 2008;2:113-35 pubmed publisher
    ..It is shown that despite of the partial simplification of the mesoscopic nature of regulatory networks such processes are suitable to reveal the intrinsic noise effects because of the low copy numbers of genes. ..
  14. Tavva V, Palli S, Dinkins R, Collins G. Applications of EcR gene switch technology in functional genomics. Arch Insect Biochem Physiol. 2007;65:164-79 pubmed
  15. Hassan M, Saini S, Gordon J, Van Wijnen A, Montecino M, Stein J, et al. Molecular switches involving homeodomain proteins, HOXA10 and RUNX2 regulate osteoblastogenesis. Cells Tissues Organs. 2009;189:122-5 pubmed publisher
    ..These findings reveal the requirement for multiple levels of control for the appropriate timing of osteoblast-related gene expression. ..
  16. Lau A, Villeneuve N, Sun Z, Wong P, Zhang D. Dual roles of Nrf2 in cancer. Pharmacol Res. 2008;58:262-70 pubmed publisher
    ..This review is primarily focused on the role of Nrf2 in cancer, with emphasis on the recent findings indicating the cancer promoting function of Nrf2 and its role in acquired chemoresistance. ..
  17. Larrain J, Oelgeschlager M, Ketpura N, Reversade B, Zakin L, De Robertis E. Proteolytic cleavage of Chordin as a switch for the dual activities of Twisted gastrulation in BMP signaling. Development. 2001;128:4439-47 pubmed
  18. Gordon A, Halliday J, Blankschien M, Burns P, Yatagai F, Herman C. Transcriptional infidelity promotes heritable phenotypic change in a bistable gene network. PLoS Biol. 2009;7:e44 pubmed publisher
    ..Whereas DNA errors allow genetic space to be explored, RNA errors may allow epigenetic or expression space to be sampled. Thus, RNA infidelity should also be considered in the heritable origin of altered or aberrant cell behaviour. ..
  19. Hernday A, Braaten B, Broitman Maduro G, Engelberts P, Low D. Regulation of the pap epigenetic switch by CpxAR: phosphorylated CpxR inhibits transition to the phase ON state by competition with Lrp. Mol Cell. 2004;16:537-47 pubmed
    ..CpxAR-dependent repression of pap transcription is also observed in response to alkaline growth conditions. These results provide insight into a mechanism for environmental control of epigenetically regulated gene expression. ..
  20. Blomfield I, Calie P, Eberhardt K, McClain M, Eisenstein B. Lrp stimulates phase variation of type 1 fimbriation in Escherichia coli K-12. J Bacteriol. 1993;175:27-36 pubmed
    ..We believe that these alterations in fimB and fimE transcription alone are unlikely to account for the sharp reduction in switching found in lrp mutants. ..
  21. Algarte M, Kwon H, Genin P, Hiscott J. Identification by in vivo genomic footprinting of a transcriptional switch containing NF-kappaB and Sp1 that regulates the IkappaBalpha promoter. Mol Cell Biol. 1999;19:6140-53 pubmed
    ..These observations provide the first in vivo characterization of a promoter proximal transcriptional switch involving NF-kappaB and Sp1 that is essential for autoregulation of the IkappaBalpha promoter. ..
  22. Kim H, Pomeroy S, Whoriskey W, Pawlitzky I, Benowitz L, Sicinski P, et al. A developmentally regulated switch directs regenerative growth of Schwann cells through cyclin D1. Neuron. 2000;26:405-16 pubmed
    ..Even axonal regrowth into the distal zone of a nerve crush injury is not markedly impaired in cyclin D1-/- mice. ..
  23. Katsantoni E, Langeveld A, Wai A, Drabek D, Grosveld F, Anagnou N, et al. Persistent gamma-globin expression in adult transgenic mice is mediated by HPFH-2, HPFH-3, and HPFH-6 breakpoint sequences. Blood. 2003;102:3412-9 pubmed
    ..Thus, our observations provide support for a model whereby HPFH conditions arise from the juxtaposition of enhancers as well as permissive chromatin subdomains in the vicinity of the gamma-globin genes. ..
  24. Ham T, Lee S, Keasling J, Arkin A. A tightly regulated inducible expression system utilizing the fim inversion recombination switch. Biotechnol Bioeng. 2006;94:1-4 pubmed
    ..These characteristics make our system suitable for large-scale expression or for production of toxic proteins. ..
  25. Lou C, Yang X, Liu X, He B, Ouyang Q. A quantitative study of lambda-phage SWITCH and its components. Biophys J. 2007;92:2685-93 pubmed
    ..Furthermore, the model explains the weak role of Cro protein and probably sheds light on the evolution of lambda-Cro protein, which is known to be structurally distinct from the other Cros in lambdoid family members. ..
  26. Alexander M, Mlynarczyk Evans S, Royce Tolland M, Plocik A, Kalantry S, Magnuson T, et al. Differences between homologous alleles of olfactory receptor genes require the Polycomb Group protein Eed. J Cell Biol. 2007;179:269-76 pubmed
    ..These results suggest a common mechanism for random monoallelic expression on autosomes and the X chromosome, and implicate Eed in establishing differences between homologous OR loci before and after differentiation. ..
  27. Jia S, Yamada T, Grewal S. Heterochromatin regulates cell type-specific long-range chromatin interactions essential for directed recombination. Cell. 2004;119:469-80 pubmed
    ..Our analyses implicate heterochromatin in long-range regulatory interactions and suggest that heterochromatin imposes at the mating-type region structural organization that is important for the donor-choice mechanism. ..
  28. Andrecut M, Cloud D, Kauffman S. Monte Carlo simulation of a simple gene network yields new evolutionary insights. J Theor Biol. 2008;250:468-74 pubmed
  29. Toniatti C, Bujard H, Cortese R, Ciliberto G. Gene therapy progress and prospects: transcription regulatory systems. Gene Ther. 2004;11:649-57 pubmed
    ..The development of ligand-dependent transcription regulatory systems is thus of great importance. Here, we summarize the most recent progress in the field. ..
  30. Gherardi G, Whitney C, Facklam R, Beall B. Major related sets of antibiotic-resistant Pneumococci in the United States as determined by pulsed-field gel electrophoresis and pbp1a-pbp2b-pbp2x-dhf restriction profiles. J Infect Dis. 2000;181:216-29 pubmed publisher
    ..Divergent capsular types among isolates with identical PBP gene-dhf profiles and related PFGE types indicated several instances of capsular serotype switching...
  31. Yamada Inagawa T, Klar A, Dalgaard J. Schizosaccharomyces pombe switches mating type by the synthesis-dependent strand-annealing mechanism. Genetics. 2007;177:255-65 pubmed
    ..We show that in such strains wild-type P-cassette DNA is efficiently generated at mat1 through heteroduplex DNA formation and repair. The present data provide an in vivo genetic test of the proposed molecular recombination mechanism. ..
  32. Diep C, Tao X, Pilauri V, Losiewicz M, Blank T, Hopper J. Genetic evidence for sites of interaction between the Gal3 and Gal80 proteins of the Saccharomyces cerevisiae GAL gene switch. Genetics. 2008;178:725-36 pubmed publisher
    ..The striking colocalization of intergenic suppressor residues and Gal80 nonbinder residues identifies a Gal3 surface that likely interacts with Gal80. ..
  33. Zhou D, Liu K, Sun C, Pawlik K, Townes T. KLF1 regulates BCL11A expression and gamma- to beta-globin gene switching. Nat Genet. 2010;42:742-4 pubmed publisher
    ..Controlled knockdown of KLF1 in adult erythroid progenitors may provide a method to activate fetal hemoglobin expression in individuals with beta-thalassemia or sickle cell disease. ..
  34. Foley K, Engel J. Individual stage selector element mutations lead to reciprocal changes in beta- vs. epsilon-globin gene transcription: genetic confirmation of promoter competition during globin gene switching. Genes Dev. 1992;6:730-44 pubmed
  35. Weber W, Fussenegger M. Novel gene switches. Handb Exp Pharmacol. 2007;:73-105 pubmed
    ..This article will conclude with an overview of how the different gene switches have been applied in gene therapy studies, bioengineering and drug discovery. ..
  36. Guntas G, Mansell T, Kim J, Ostermeier M. Directed evolution of protein switches and their application to the creation of ligand-binding proteins. Proc Natl Acad Sci U S A. 2005;102:11224-9 pubmed
    ..The transplantation of these mutations into wild-type MBP converted MBP into a "sucrose-binding protein," illustrating the switches potential as a tool to rapidly identify ligand-binding proteins. ..
  37. Klar A, Bonaduce M. swi6, a gene required for mating-type switching, prohibits meiotic recombination in the mat2-mat3 "cold spot" of fission yeast. Genetics. 1991;129:1033-42 pubmed
    ..This finding, combined with the additional result that switching primarily occurs intrachromosomally, suggests that the donor loci are made accessible for switching by folding them onto mat1, thus causing the cold spot of recombination. ..
  38. Kay J, Baier H. Out-foxing fate; molecular switches create neuronal diversity in the retina. Neuron. 2004;43:759-60 pubmed
    ..Two reports in this issue of Neuron reveal two transcription factors (Foxn4 and Bhlhb4) that contribute to the development of this remarkable cellular diversity. ..
  39. Grewal S, Han B, Johnstone K. Identification and characterization of a locus which regulates multiple functions in Pseudomonas tolaasii, the cause of brown blotch disease of Agaricus bisporus. J Bacteriol. 1995;177:4658-68 pubmed
    ..Analysis of pheN expression with a pheN::lacZ fusion demonstrated that expression is regulated by environmental factors. These results are related to a model for control for phenotypic variation in P. tolaasii. ..
  40. Thorsted P, Shah D, Macartney D, Kostelidou K, Thomas C. Conservation of the genetic switch between replication and transfer genes of IncP plasmids but divergence of the replication functions which are major host-range determinants. Plasmid. 1996;36:95-111 pubmed
    ..aeruginosa at 37 degrees C, although it did establish itself inefficiently at lower temperatures, underlining the importance of this region in the adaptation of the plasmid to the host. ..
  41. Brazhnik P, Tyson J. Cell cycle control in bacteria and yeast: a case of convergent evolution?. Cell Cycle. 2006;5:522-9 pubmed
  42. Fleck O, Michael H, Heim L. The swi4+ gene of Schizosaccharomyces pombe encodes a homologue of mismatch repair enzymes. Nucleic Acids Res. 1992;20:2271-8 pubmed
    ..A strain with a disrupted swi4+ gene was constructed and analysed with respect to the switching process. As in swi4 mutants duplications occur in the mating-type region of the swi4 (null) strain, reducing the efficiency of switching. ..
  43. Kosik K, Orecchio L, Bakalis S, Neve R. Developmentally regulated expression of specific tau sequences. Neuron. 1989;2:1389-97 pubmed
    ..Comparison of the developmentally expressed tau sequences with those sequences obtained directly from Alzheimer paired helical filaments revealed the presence of both the mature and the immature tau mRNA sequences. ..
  44. Ghim C, Almaas E. Genetic noise control via protein oligomerization. BMC Syst Biol. 2008;2:94 pubmed publisher
    ..Our results also suggest possible avenues for the design of synthetic gene circuits with tunable robustness for a wide range of engineering purposes. ..
  45. Marzi S, Fechter P, Chevalier C, Romby P, Geissmann T. RNA switches regulate initiation of translation in bacteria. Biol Chem. 2008;389:585-98 pubmed
    ..These RNA switches can temporally regulate translation, leading either to repression or to activation of protein synthesis. ..
  46. Nguyen V, Sil A. Temperature-induced switch to the pathogenic yeast form of Histoplasma capsulatum requires Ryp1, a conserved transcriptional regulator. Proc Natl Acad Sci U S A. 2008;105:4880-5 pubmed publisher
    ..Thus, Ryp1 appears to be a critical transcriptional regulator of a temperature-regulated morphologic switch in H. capsulatum. ..
  47. Broccardo C, Billings R, Andersen M, Hanneman W. Probing the control elements of the CYP1A1 switching module in H4IIE hepatoma cells. Toxicol Sci. 2005;88:82-94 pubmed
    ..Additional studies are planned to further investigate the role of PKC in the switch-like response to PCB 126. ..
  48. Pallesen L, Madsen O, Klemm P. Regulation of the phase switch controlling expression of type 1 fimbriae in Escherichia coli. Mol Microbiol. 1989;3:925-31 pubmed
    ..This suggests a regulatory mechanism, since the resulting transcript would be anti-sense to the fimE transcript. ..
  49. Honjo T, Kinoshita K, Muramatsu M. Molecular mechanism of class switch recombination: linkage with somatic hypermutation. Annu Rev Immunol. 2002;20:165-96 pubmed
    ..Mismatched bases will be corrected or fixed by mismatch repair enzymes. CSR ends are then ligated by the NHEJ system while SHM nicks are repaired by another ligation system. ..
  50. Yang Y, Pace B. Pharmacologic induction of fetal hemoglobin synthesis: cellular and molecular mechanisms. Pediatr Pathol Mol Med. 2001;20:87-106 pubmed
    ..Identifying the proteins involved in gamma gene activation by various compounds may offer a new strategy for gene therapy to cure hemoglobinopathy disorders. ..
  51. Leung B, Waddell S. Four-dimensional gene expression control: memories on the fly. Trends Neurosci. 2004;27:511-3 pubmed
    ..Two recent papers describe implementation of different but related technologies that now provide this missing element in fly behavioral research. ..
  52. Guntas G, Mitchell S, Ostermeier M. A molecular switch created by in vitro recombination of nonhomologous genes. Chem Biol. 2004;11:1483-7 pubmed
    ..The modularity of RG13 was demonstrated by increasing maltose affinity while preserving switching activity. RG13 gave rise to a novel cellular phenotype, illustrating the potential of molecular switches to rewire the cellular circuitry. ..
  53. Kashimada K, Koopman P. Sry: the master switch in mammalian sex determination. Development. 2010;137:3921-30 pubmed publisher
    ..Here, we discuss the cascade of events triggered by SRY and the mechanisms that reinforce the differentiation of the testes in males while actively inhibiting ovarian development. ..