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Regulator gene

January 24, 2023

A regulator gene, regulator, or regulatory gene is a gene involved in controlling the expression of one or more other genes. Regulatory sequences, which encode regulatory genes, are often at the five prime end (5') to the start site of transcription of the gene they regulate. In addition, these sequences can also be found at the three prime end (3') to the transcription start site. In both cases, whether the regulatory sequence occurs before (5') or after (3') the gene it regulates, the sequence is often many kilobases away from the transcription start site. A regulator gene may encode a protein, or it may work at the level of RNA, as in the case of genes encoding microRNAs. An example of a regulator gene is a gene that codes for a repressor protein that inhibits the activity of an operator (a gene which binds repressor proteins thus inhibiting the translation of RNA to protein via RNA polymerase).[1]

Gene regulatory pathway

In prokaryotes, regulator genes often code for repressor proteins. Repressor proteins bind to operators or promoters, preventing RNA polymerase from transcribing RNA. They are usually constantly expressed so the cell always has a supply of repressor molecules on hand.[2] Inducers cause repressor proteins to change shape or otherwise become unable to bind DNA, allowing RNA polymerase to continue transcription. Regulator genes can be located within an operon, adjacent to it, or far away from it.[3]

Other regulatory genes code for activator proteins. An activator binds to a site on the DNA molecule and causes an increase in transcription of a nearby gene. In prokaryotes, a well-known activator protein is the catabolite activator protein (CAP), involved in positive control of the lac operon.

In the regulation of gene expression, studied in evolutionary developmental biology (evo-devo), both activators and repressors play important roles.[4]

Regulatory genes can also be described as positive or negative regulators, based on the environmental conditions that surround the cell. Positive regulators are regulatory elements that permit RNA polymerase binding to the promoter region, thus allowing transcription to occur. In terms of the lac operon, the positive regulator would be the CRP-cAMP complex that must be bound close to the site of the start of transcription of the lac genes. The binding of this positive regulator allows RNA polymerase to bind successfully to the promoter of the lac gene sequence which advances the transcription of lac genes; lac Z, lac Y, and lac A. Negative regulators are regulatory elements which obstruct the binding of RNA polymerase to the promoter region, thus repressing transcription. In terms of the lac operon, the negative regulator would be the lac repressor which binds to the promoter in the same site that RNA polymerase normally binds. The binding of the lac repressor to RNA polymerase's binding site inhibits the transcription of the lac genes. Only when a corepressor is bound to the lac repressor will the binding site be free for RNA polymerase to carry out transcription of the lac genes.[5][6][7]

Gene regulatory elements

Promoters reside at the beginning of the gene and serve as the site where the transcription machinery assembles and transcription of the gene begins. Enhancers turn on the promoters at specific locations, times, and levels and can be simply defined as the “promoters of the promoter.” Silencers are thought to turn off gene expression at specific time points and locations. Insulators, also called boundary elements, are DNA sequences that create cis-regulatory boundaries that prevent the regulatory elements of one gene from affecting neighboring genes. The general dogma is that these regulatory elements get activated by the binding of transcription factors, proteins that bind to specific DNA sequences, and control mRNA transcription. There could be several transcription factors that need to bind to one regulatory element in order to activate it. In addition, several other proteins, called transcription cofactors, bind to the transcription factors themselves to control transcription.[8][9]

Negative regulators

Negative regulators act to prevent transcription or translation. Examples such as cFLIP suppress cell death mechanisms leading to pathological disorders like cancer, and thus play a crucial role in drug resistance. Circumvention of such actors is a challenge in cancer therapy.[10] Negative regulators of cell death in cancer include cFLIP, Bcl2 family, Survivin, HSP, IAP, NF-κB, Akt, mTOR, and FADD.[10]

Detection

There are several different techniques to detect regulatory genes, but of the many there are a certain few that are used more frequently than others. One of these select few is called ChIP-chip. ChIP-chip is an in vivo technique used to determine genomic binding sites for transcription factors in two component system response regulators. In vitro microarray based assay (DAP-chip) can be used to determine gene targets and functions of two component signal transduction systems. This assay takes advantage of the fact that response regulators can be phosphorylated and thus activated in vitro using small molecule donors like acetyl phosphate.[11][12]

Phylogenetic footprinting

Phylogenetic footprinting is a technique that utilizes multiple sequence alignments to determine locations of conserved sequences such as regulatory elements. Along with multiple sequence alignments, phylogenetic footprinting also requires statistical rates of conserved and non-conserved sequences. Using the information provided by multiple sequence alignments and statistical rates, one can identify the best conserved motifs in the orthologous regions of interest.[13][14]

References

  1. ^ "Regulatory gene - Biology-Online Dictionary". www.biology-online.org. Retrieved 2016-02-06.
  2. ^ Campbell Biology—Concepts and Connections 7th Edition. Pearson Education. 2009. pp. 210–211.
  3. ^ Mayer, Gene. "BACTERIOLOGY - CHAPTER NINE GENETIC REGULATORY MECHANISMS". Microbiology and Immunology Online. University of South Carolina School of Medicine. Retrieved 30 December 2012.
  4. ^ Suzuki, David (2005). Introduction to Genetic Analysis. San Francisco: W.H. Freeman. ISBN 978-0-7167-4939-4.
  5. ^ Casadaban, Malcolm J. (1976-07-05). "Regulation of the regulatory gene for the arabinose pathway, araC". Journal of Molecular Biology. 104 (3): 557–566. doi:10.1016/0022-2836(76)90120-0. PMID 781294.
  6. ^ Wong, Oi Kwan; Guthold, Martin; Erie, Dorothy A; Gelles, Jeff (2008). "Interconvertible Lac Repressor–DNA Loops Revealed by Single-Molecule Experiments". PLOS Biology. 6 (9): e232. doi:10.1371/journal.pbio.0060232. PMC 2553838. PMID 18828671.
  7. ^ Jiang, Xiaofeng; Pan, Hui; Nabhan, Joseph F.; Krishnan, Ramaswamy; Koziol-White, Cynthia; Panettieri, Reynold A.; Lu, Quan (2012-05-01). "A novel EST-derived RNAi screen reveals a critical role for farnesyl diphosphate synthase in β2-adrenergic receptor internalization and down-regulation". The FASEB Journal. 26 (5): 1995–2007. doi:10.1096/fj.11-193870. ISSN 0892-6638. PMC 3336790. PMID 22278941.
  8. ^ Khan, Arshad H.; Lin, Andy; Smith, Desmond J. (2012-09-24). "Discovery and Characterization of Human Exonic Transcriptional Regulatory Elements". PLOS ONE. 7 (9): e46098. Bibcode:2012PLoSO...746098K. doi:10.1371/journal.pone.0046098. ISSN 1932-6203. PMC 3454335. PMID 23029400.
  9. ^ Ahituv, Nadav (2012). Ahituv, Nadav (ed.). Gene Regulatory Elements. Gene Regulatory Sequences and Human Disease (2012). doi:10.1007/978-1-4614-1683-8. ISBN 978-1-4614-1682-1. S2CID 40483427.
  10. ^ a b Razaghi, Ali; Heimann, Kirsten; Schaeffer, Patrick M.; Gibson, Spencer B. (2018-01-10). "Negative regulators of cell death pathways in cancer: perspective on biomarkers and targeted therapies". Apoptosis. 23 (2): 93–112. doi:10.1007/s10495-018-1440-4. ISSN 1360-8185. PMID 29322476. S2CID 3424489.
  11. ^ Kogelman, Lisette J A; Cirera, Susanna; Zhernakova, Daria V; Fredholm, Merete; Franke, Lude; Kadarmideen, Haja N (2014-09-30). "Identification of co-expression gene networks, regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model". BMC Medical Genomics. 7: 57. doi:10.1186/1755-8794-7-57. ISSN 1755-8794. PMC 4183073. PMID 25270054.
  12. ^ Rajeev, Lara; Luning, Eric G.; Mukhopadhyay, Aindrila (2014). "DNA-affinity-purified Chip (DAP-chip) Method to Determine Gene Targets for Bacterial Two component Regulatory Systems | Protocol". Journal of Visualized Experiments (89): e51715. doi:10.3791/51715. PMC 4233932. PMID 25079303. Retrieved 2016-04-08.
  13. ^ Satija, Rahul; Novák, Ádám; Miklós, István; Lyngsø, Rune; Hein, Jotun (2009-08-28). "BigFoot: Bayesian alignment and phylogenetic footprinting with MCMC". BMC Evolutionary Biology. 9: 217. doi:10.1186/1471-2148-9-217. ISSN 1471-2148. PMC 2744684. PMID 19715598.
  14. ^ Blanchette, Mathieu; Tompa, Martin (2002-05-01). "Discovery of Regulatory Elements by a Computational Method for Phylogenetic Footprinting". Genome Research. 12 (5): 739–748. doi:10.1101/gr.6902. ISSN 1088-9051. PMC 186562. PMID 11997340.

External links

January 24, 2023
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A regulator gene regulator or regulatory gene is a gene involved in controlling the expression of one or more other genes Regulatory sequences which encode regulatory genes are often at the five prime end 5 to the start site of transcription of the gene they regulate In addition these sequences can also be found at the three prime end 3 to the transcription start site In both cases whether the regulatory sequence occurs before 5 or after 3 the gene it regulates the sequence is often many kilobases away from the transcription start site A regulator gene may encode a protein or it may work at the level of RNA as in the case of genes encoding microRNAs An example of a regulator gene is a gene that codes for a repressor protein that inhibits the activity of an operator a gene which binds repressor proteins thus inhibiting the translation of RNA to protein via RNA polymerase 1 Gene regulatory pathway In prokaryotes regulator genes often code for repressor proteins Repressor proteins bind to operators or promoters preventing RNA polymerase from transcribing RNA They are usually constantly expressed so the cell always has a supply of repressor molecules on hand 2 Inducers cause repressor proteins to change shape or otherwise become unable to bind DNA allowing RNA polymerase to continue transcription Regulator genes can be located within an operon adjacent to it or far away from it 3 Other regulatory genes code for activator proteins An activator binds to a site on the DNA molecule and causes an increase in transcription of a nearby gene In prokaryotes a well known activator protein is the catabolite activator protein CAP involved in positive control of the lac operon In the regulation of gene expression studied in evolutionary developmental biology evo devo both activators and repressors play important roles 4 Regulatory genes can also be described as positive or negative regulators based on the environmental conditions that surround the cell Positive regulators are regulatory elements that permit RNA polymerase binding to the promoter region thus allowing transcription to occur In terms of the lac operon the positive regulator would be the CRP cAMP complex that must be bound close to the site of the start of transcription of the lac genes The binding of this positive regulator allows RNA polymerase to bind successfully to the promoter of the lac gene sequence which advances the transcription of lac genes lac Z lac Y and lac A Negative regulators are regulatory elements which obstruct the binding of RNA polymerase to the promoter region thus repressing transcription In terms of the lac operon the negative regulator would be the lac repressor which binds to the promoter in the same site that RNA polymerase normally binds The binding of the lac repressor to RNA polymerase s binding site inhibits the transcription of the lac genes Only when a corepressor is bound to the lac repressor will the binding site be free for RNA polymerase to carry out transcription of the lac genes 5 6 7 Contents 1 Gene regulatory elements 2 Negative regulators 3 Detection 4 Phylogenetic footprinting 5 References 6 External linksGene regulatory elements EditPromoters reside at the beginning of the gene and serve as the site where the transcription machinery assembles and transcription of the gene begins Enhancers turn on the promoters at specific locations times and levels and can be simply defined as the promoters of the promoter Silencers are thought to turn off gene expression at specific time points and locations Insulators also called boundary elements are DNA sequences that create cis regulatory boundaries that prevent the regulatory elements of one gene from affecting neighboring genes The general dogma is that these regulatory elements get activated by the binding of transcription factors proteins that bind to specific DNA sequences and control mRNA transcription There could be several transcription factors that need to bind to one regulatory element in order to activate it In addition several other proteins called transcription cofactors bind to the transcription factors themselves to control transcription 8 9 Negative regulators EditNegative regulators act to prevent transcription or translation Examples such as cFLIP suppress cell death mechanisms leading to pathological disorders like cancer and thus play a crucial role in drug resistance Circumvention of such actors is a challenge in cancer therapy 10 Negative regulators of cell death in cancer include cFLIP Bcl2 family Survivin HSP IAP NF kB Akt mTOR and FADD 10 Detection EditThere are several different techniques to detect regulatory genes but of the many there are a certain few that are used more frequently than others One of these select few is called ChIP chip ChIP chip is an in vivo technique used to determine genomic binding sites for transcription factors in two component system response regulators In vitro microarray based assay DAP chip can be used to determine gene targets and functions of two component signal transduction systems This assay takes advantage of the fact that response regulators can be phosphorylated and thus activated in vitro using small molecule donors like acetyl phosphate 11 12 Phylogenetic footprinting EditPhylogenetic footprinting is a technique that utilizes multiple sequence alignments to determine locations of conserved sequences such as regulatory elements Along with multiple sequence alignments phylogenetic footprinting also requires statistical rates of conserved and non conserved sequences Using the information provided by multiple sequence alignments and statistical rates one can identify the best conserved motifs in the orthologous regions of interest 13 14 References Edit Regulatory gene Biology Online Dictionary www biology online org Retrieved 2016 02 06 Campbell Biology Concepts and Connections 7th Edition Pearson Education 2009 pp 210 211 Mayer Gene BACTERIOLOGY CHAPTER NINE GENETIC REGULATORY MECHANISMS Microbiology and Immunology Online University of South Carolina School of Medicine Retrieved 30 December 2012 Suzuki David 2005 Introduction to Genetic Analysis San Francisco W H Freeman ISBN 978 0 7167 4939 4 Casadaban Malcolm J 1976 07 05 Regulation of the regulatory gene for the arabinose pathway araC Journal of Molecular Biology 104 3 557 566 doi 10 1016 0022 2836 76 90120 0 PMID 781294 Wong Oi Kwan Guthold Martin Erie Dorothy A Gelles Jeff 2008 Interconvertible Lac Repressor DNA Loops Revealed by Single Molecule Experiments PLOS Biology 6 9 e232 doi 10 1371 journal pbio 0060232 PMC 2553838 PMID 18828671 Jiang Xiaofeng Pan Hui Nabhan Joseph F Krishnan Ramaswamy Koziol White Cynthia Panettieri Reynold A Lu Quan 2012 05 01 A novel EST derived RNAi screen reveals a critical role for farnesyl diphosphate synthase in b2 adrenergic receptor internalization and down regulation The FASEB Journal 26 5 1995 2007 doi 10 1096 fj 11 193870 ISSN 0892 6638 PMC 3336790 PMID 22278941 Khan Arshad H Lin Andy Smith Desmond J 2012 09 24 Discovery and Characterization of Human Exonic Transcriptional Regulatory Elements PLOS ONE 7 9 e46098 Bibcode 2012PLoSO 746098K doi 10 1371 journal pone 0046098 ISSN 1932 6203 PMC 3454335 PMID 23029400 Ahituv Nadav 2012 Ahituv Nadav ed Gene Regulatory Elements Gene Regulatory Sequences and Human Disease 2012 doi 10 1007 978 1 4614 1683 8 ISBN 978 1 4614 1682 1 S2CID 40483427 a b Razaghi Ali Heimann Kirsten Schaeffer Patrick M Gibson Spencer B 2018 01 10 Negative regulators of cell death pathways in cancer perspective on biomarkers and targeted therapies Apoptosis 23 2 93 112 doi 10 1007 s10495 018 1440 4 ISSN 1360 8185 PMID 29322476 S2CID 3424489 Kogelman Lisette J A Cirera Susanna Zhernakova Daria V Fredholm Merete Franke Lude Kadarmideen Haja N 2014 09 30 Identification of co expression gene networks regulatory genes and pathways for obesity based on adipose tissue RNA Sequencing in a porcine model BMC Medical Genomics 7 57 doi 10 1186 1755 8794 7 57 ISSN 1755 8794 PMC 4183073 PMID 25270054 Rajeev Lara Luning Eric G Mukhopadhyay Aindrila 2014 DNA affinity purified Chip DAP chip Method to Determine Gene Targets for Bacterial Two component Regulatory Systems Protocol Journal of Visualized Experiments 89 e51715 doi 10 3791 51715 PMC 4233932 PMID 25079303 Retrieved 2016 04 08 Satija Rahul Novak Adam Miklos Istvan Lyngso Rune Hein Jotun 2009 08 28 BigFoot Bayesian alignment and phylogenetic footprinting with MCMC BMC Evolutionary Biology 9 217 doi 10 1186 1471 2148 9 217 ISSN 1471 2148 PMC 2744684 PMID 19715598 Blanchette Mathieu Tompa Martin 2002 05 01 Discovery of Regulatory Elements by a Computational Method for Phylogenetic Footprinting Genome Research 12 5 739 748 doi 10 1101 gr 6902 ISSN 1088 9051 PMC 186562 PMID 11997340 External links EditPlant Transcription Factor Database Regulator Gene at the US National Library of Medicine Medical Subject Headings MeSH http www news medical net life sciences Gene Expression Techniques aspx http www britannica com science regulator gene https www boundless com biology textbooks boundless biology textbook gene expression 16 regulation of gene expression 111 prokaryotic versus eukaryotic gene expression 453 11678 Retrieved from https en wikipedia org w index php title Regulator gene amp oldid 1077129471, wikipedia, wiki, book, books, library,

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