Regulation of Gene Expression

Regulation of Gene Expression tài liệu, giáo án, bài giảng , luận văn, luận án, đồ án, bài tập lớn về tất cả các lĩnh vự...

BioMed Central Page 1 of 9 (page number not for citation purposes) Virology Journal Open Access Research In vitro dynamics of HIV-1 BF intersubtype recombinants genomic regions involved in the regulation of gene expression Mauricio G Carobene* † , Christian Rodríguez Rodrígues † , Cristian A De Candia, Gabriela Turk and Horacio Salomón Address: National Reference Center for AIDS, Department of Microbiology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina Email: Mauricio G Carobene* - mcarobe@fmed.uba.ar; Christian Rodríguez Rodrígues - crodriguez@fmed.uba.ar; Cristian A De Candia - cristiandecandia@gmail.com; Gabriela Turk - gturk@fmed.uba.ar; Horacio Salomón - hsalomon@fmed.uba.ar * Corresponding author †Equal contributors Abstract HIV-1 intersubtype recombination is a very common phenomenon that has been shown to frequently affect different viral genomic regions. Vpr and Tat are viral proteins known to interact with viral promoter (LTR) during the replication cycle. This interaction is mainly involved in the regulation of viral gene expression, so, any structural changes in the LTR and/or these regulatory proteins may have an important impact on viral replication and spread. It has been reported that these genetic structures underwent recombination in BF variants widely spread in South America. To gain more insight of the consequences of the BF intersubtype recombination phenomenon on these different but functionally related genomic regions we designed and performed and in vitro study that allowed the detection and recovery of intersubtype recombinants sequences and its subsequent analysis. Our results indicate that recombination affects differentially these regions, showing evidence of a time-space relationship between the changes observed in the viral promoter and the ones observed in the Vpr/Tat coding region. This supports the idea of intersubtype recombination as a mechanism that promotes biological adaptation and compensates fitness variations. Background Recombination among retroviral genomes was first docu- mented in avian tumour viruses by Vogt et al in 1971 [1] and subsequently in other retroviruses [2,3]. This phe- nomenon occurs before integration at a high rate along the reverse transcription stage. It is dependent on co-pack- aging of two different viral genomes [4,5], and provides a powerful mechanism to rapidly increase viral sequence diversity [6-8]. It has now become evident that HIV recombination is a very common event and in areas with different circulating subtypes, recombinant viruses may even predominate. To date, more than 40 circulating recombinant forms (CRFs) have been described (Los Alamos HIV Database) reinforc- ing the idea that HIV-1 intersubtype recombination is a very effective way to augment variability and to improve viral fitness [9]. In previous studies, our results showed that the epidemic in Argentina is characterized by the high prevalence of a Published: 16 July 2009 Virology Journal 2009, 6:107 doi:10.1186/1743-422X-6-107 Received: 14 May 2009 Accepted: 16 July 2009 This article is available from: http://www.virologyj.com/content/6/1/107 © 2009 Carobene et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Virology Journal 2009, 6:107 http://www.virologyj.com/content/6/1/107 Page 2 of 9 (page number not for citation purposes) circulating recombinant form, CRF12_ BF and many related BF recombinant forms [10-13]. Molecular studies on these variants showed that recombination frequently affected genomic regions involved in regulating viral gene expression, replication, and interaction with the host immune system, eventually leading to remarkable func- tional consequences [14,15]. Transcriptional activation Regulation of Gene Expression Regulation of Gene Expression Bởi: OpenStaxCollege For a cell to function properly, necessary proteins must be synthesized at the proper time All cells control or regulate the synthesis of proteins from information encoded in their DNA The process of turning on a gene to produce RNA and protein is called gene expression Whether in a simple unicellular organism or a complex multi-cellular organism, each cell controls when and how its genes are expressed For this to occur, there must be a mechanism to control when a gene is expressed to make RNA and protein, how much of the protein is made, and when it is time to stop making that protein because it is no longer needed The regulation of gene expression conserves energy and space It would require a significant amount of energy for an organism to express every gene at all times, so it is more energy efficient to turn on the genes only when they are required In addition, only expressing a subset of genes in each cell saves space because DNA must be unwound from its tightly coiled structure to transcribe and translate the DNA Cells would have to be enormous if every protein were expressed in every cell all the time The control of gene expression is extremely complex Malfunctions in this process are detrimental to the cell and can lead to the development of many diseases, including cancer Prokaryotic versus Eukaryotic Gene Expression To understand how gene expression is regulated, we must first understand how a gene codes for a functional protein in a cell The process occurs in both prokaryotic and eukaryotic cells, just in slightly different manners Prokaryotic organisms are single-celled organisms that lack a cell nucleus, and their DNA therefore floats freely in the cell cytoplasm To synthesize a protein, the processes of transcription and translation occur almost simultaneously When the resulting protein is no longer needed, transcription stops As a result, the primary method to control what type of protein and how much of each protein is expressed in a prokaryotic cell is the 1/5 Regulation of Gene Expression regulation of DNA transcription All of the subsequent steps occur automatically When more protein is required, more transcription occurs Therefore, in prokaryotic cells, the control of gene expression is mostly at the transcriptional level Eukaryotic cells, in contrast, have intracellular organelles that add to their complexity In eukaryotic cells, the DNA is contained inside the cell’s nucleus and there it is transcribed into RNA The newly synthesized RNA is then transported out of the nucleus into the cytoplasm, where ribosomes translate the RNA into protein The processes of transcription and translation are physically separated by the nuclear membrane; transcription occurs only within the nucleus, and translation occurs only outside the nucleus in the cytoplasm The regulation of gene expression can occur at all stages of the process ([link]) Regulation may occur when the DNA is uncoiled and loosened from nucleosomes to bind transcription factors (epigenetic level), when the RNA is transcribed (transcriptional level), when the RNA is processed and exported to the cytoplasm after it is transcribed (post-transcriptional level), when the RNA is translated into protein (translational level), or after the protein has been made (posttranslational level) Prokaryotic transcription and translation occur simultaneously in the cytoplasm, and regulation occurs at the transcriptional level Eukaryotic gene expression is regulated during transcription and RNA processing, which take place in the nucleus, and during protein translation, which takes place in the cytoplasm Further regulation may occur through post-translational modifications of proteins The differences in the regulation of gene expression between prokaryotes and eukaryotes are summarized in [link] The regulation of gene expression is discussed in detail in subsequent modules 2/5 Regulation of Gene Expression Differences in the Regulation of Gene Expression of Prokaryotic and Eukaryotic Organisms Prokaryotic organisms Eukaryotic organisms Lack nucleus Contain nucleus DNA is found in the cytoplasm DNA is confined to the nuclear compartment RNA transcription and protein formation occur almost simultaneously RNA transcription occurs prior to protein formation, and it takes place in the nucleus Translation of RNA to protein occurs in the cytoplasm Gene expression is regulated primarily at the transcriptional level Gene expression is regulated at many levels (epigenetic, transcriptional, nuclear shuttling, posttranscriptional, translational, and post-translational) Evolution Connection Evolution of Gene RegulationProkaryotic cells can only regulate gene expression by controlling the amount of transcription As eukaryotic cells evolved, the complexity of the control of gene expression increased For example, with the evolution of eukaryotic cells came compartmentalization of important ...BioMed Central Page 1 of 9 (page number not for citation purposes) Virology Journal Open Access Research In vitro dynamics of HIV-1 BF intersubtype recombinants genomic regions involved in the regulation of gene expression Mauricio G Carobene* † , Christian Rodríguez Rodrígues † , Cristian A De Candia, Gabriela Turk and Horacio Salomón Address: National Reference Center for AIDS, Department of Microbiology, School of Medicine, University of Buenos Aires, Buenos Aires, Argentina Email: Mauricio G Carobene* - mcarobe@fmed.uba.ar; Christian Rodríguez Rodrígues - crodriguez@fmed.uba.ar; Cristian A De Candia - cristiandecandia@gmail.com; Gabriela Turk - gturk@fmed.uba.ar; Horacio Salomón - hsalomon@fmed.uba.ar * Corresponding author †Equal contributors Abstract HIV-1 intersubtype recombination is a very common phenomenon that has been shown to frequently affect different viral genomic regions. Vpr and Tat are viral proteins known to interact with viral promoter (LTR) during the replication cycle. This interaction is mainly involved in the regulation of viral gene expression, so, any structural changes in the LTR and/or these regulatory proteins may have an important impact on viral replication and spread. It has been reported that these genetic structures underwent recombination in BF variants widely spread in South America. To gain more insight of the consequences of the BF intersubtype recombination phenomenon on these different but functionally related genomic regions we designed and performed and in vitro study that allowed the detection and recovery of intersubtype recombinants sequences and its subsequent analysis. Our results indicate that recombination affects differentially these regions, showing evidence of a time-space relationship between the changes observed in the viral promoter and the ones observed in the Vpr/Tat coding region. This supports the idea of intersubtype recombination as a mechanism that promotes biological adaptation and compensates fitness variations. Background Recombination among retroviral genomes was first docu- mented in avian tumour viruses by Vogt et al in 1971 [1] and subsequently in other retroviruses [2,3]. This phe- nomenon occurs before integration at a high rate along the reverse transcription stage. It is dependent on co-pack- aging of two different viral genomes [4,5], and provides a powerful mechanism to rapidly increase viral sequence diversity [6-8]. It has now become evident that HIV recombination is a very common event and in areas with different circulating subtypes, recombinant viruses may even predominate. To date, more than 40 circulating recombinant forms (CRFs) have been described (Los Alamos HIV Database) reinforc- ing the idea that HIV-1 intersubtype recombination is a very effective way to augment variability and to improve viral fitness [9]. In previous studies, our results showed that the epidemic in Argentina is characterized by the high prevalence of a Published: 16 July 2009 Virology Journal 2009, 6:107 doi:10.1186/1743-422X-6-107 Received: 14 May 2009 Accepted: 16 July 2009 This article is available from: http://www.virologyj.com/content/6/1/107 © 2009 Carobene et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0 ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Virology Journal 2009, 6:107 http://www.virologyj.com/content/6/1/107 Page 2 of 9 (page number not for citation purposes) circulating recombinant form, CRF12_ BF and many related BF recombinant forms [10-13]. Molecular studies on these variants showed that recombination frequently affected genomic regions involved in regulating viral gene expression, replication, and interaction with the host immune system, eventually leading to remarkable func- tional consequences [14,15]. Transcriptional activation Genome Biology 2007, 8:R189 Open Access 2007Coleet al.Volume 8, Issue 9, Article R189 Research Social regulation of gene expression in human leukocytes Steve W Cole *†‡ , Louise C Hawkley § , Jesusa M Arevalo * , Caroline Y Sung † , Robert M Rose ¶ and John T Cacioppo § Addresses: * Department of Medicine, Division of Hematology-Oncology, UCLA School of Medicine, Los Angeles CA 90095-1678, USA. † UCLA AIDS Institute, UCLA Molecular Biology Institute, Jonsson Comprehensive Cancer Center. ‡ Norman Cousins Center. § Department of Psychology, and Center for Cognitive and Social Neuroscience, University of Chicago. ¶ Institute for Medical Humanities, University of Texas Medical Branch at Galveston, and the John D and Catherine T MacArthur Foundation. Correspondence: Steve W Cole. Email: coles@ucla.edu © 2007 Cole et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Effects of loneliness on gene expression<p>Analysis of differentially expressed in circulating leukocytes from people who chronically experienced high versus low levels of subjec-tive social isolation (loneliness) revealed over-expression of some anti-inflammatory genes and under-expression of some pro-inflamma-tory genes.</p> Abstract Background: Social environmental influences on human health are well established in the epidemiology literature, but their functional genomic mechanisms are unclear. The present study analyzed genome-wide transcriptional activity in people who chronically experienced high versus low levels of subjective social isolation (loneliness) to assess alterations in the activity of transcription control pathways that might contribute to increased adverse health outcomes in social isolates. Results: DNA microarray analysis identified 209 genes that were differentially expressed in circulating leukocytes from 14 high- versus low-lonely individuals, including up-regulation of genes involved in immune activation, transcription control, and cell proliferation, and down-regulation of genes supporting mature B lymphocyte function and type I interferon response. Promoter-based bioinformatic analyses showed under-expression of genes bearing anti-inflammatory glucocorticoid response elements (GREs; p = 0.032) and over-expression of genes bearing response elements for pro-inflammatory NF-κB/Rel transcription factors (p = 0.011). This reciprocal shift in pro- and anti- inflammatory signaling was not attributable to differences in circulating cortisol levels, or to other demographic, psychological, or medical characteristics. Additional transcription control pathways showing differential activity in bioinformatic analyses included the CREB/ATF, JAK/STAT, IRF1, C/ EBP, Oct, and GATA pathways. Conclusion: These data provide the first indication that human genome-wide transcriptional activity is altered in association with a social epidemiological risk factor. Impaired transcription of glucocorticoid response genes and increased activity of pro-inflammatory transcription control pathways provide a functional genomic explanation for elevated risk of inflammatory disease in individuals who experience chronically high levels of subjective social isolation. Published: 13 September 2007 Genome Biology 2007, 8:R189 (doi:10.1186/gb-2007-8-9-r189) Received: 2 March 2007 Revised: 30 July 2007 Accepted: 13 September 2007 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2007/8/9/R189 R189.2 Genome Biology 2007, Volume 8, Issue 9, Article R189 Cole et al. http://genomebiology.com/2007/8/9/R189 Genome Biology 2007, 8:R189 Background A large body of epidemiological research has linked charac- teristics of the social environment to human Genome Biology 2004, 5:R91 comment reviews reports deposited research refereed research interactions information Open Access 2004Palencharet al.Volume 5, Issue 11, Article R91 Research Genome-wide patterns of carbon and nitrogen regulation of gene expression validate the combined carbon and nitrogen (CN)-signaling hypothesis in plants Peter M Palenchar * , Andrei Kouranov † , Laurence V Lejay ‡ and Gloria M Coruzzi § Addresses: * Department of Chemistry, Rutgers University, Camden, NJ 10003, USA. † Center for Bioinformatics, University of Pennsylvania, 423 Guardian Drive, Philadelphia, PA 19104, USA. ‡ Laboratoire de Biochimie et physiologie moleculaire des plantes, 2 Place Viala, 34060 Montpellier Cedex 1, France. § Department of Biology, New York University, 100 Washington Square East, New York, NY 10003, USA. Correspondence: Gloria M Coruzzi. E-mail: gloria.coruzzi@nyu.edu © 2004 Pelenchar et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Genome-wide patterns of carbon and nitrogen regulation of gene expression validate the combined carbon and nitrogen (CN)-signaling hypothesis in plants<p>Microarray analysis and the 'InterAct class' method were used to study interactions between carbon and nitrogen signaling in <it>Ara-bidopsis</it>.</p> Abstract Background: Carbon and nitrogen are two signals that influence plant growth and development. It is known that carbon- and nitrogen-signaling pathways influence one another to affect gene expression, but little is known about which genes are regulated by interactions between carbon and nitrogen signaling or the mechanisms by which the different pathways interact. Results: Microarray analysis was used to study global changes in mRNA levels due to carbon and nitrogen in Arabidopsis thaliana. An informatic analysis using InterAct Class enabled us to classify genes on the basis of their responses to carbon or nitrogen treatments. This analysis provides in vivo evidence supporting the hypothesis that plants have a carbon/nitrogen (CN)-sensing/regulatory mechanism, as we have identified over 300 genes whose response to combined CN treatment is different from that expected from expression values due to carbon and nitrogen treatments separately. Metabolism, energy and protein synthesis were found to be significantly affected by interactions between carbon and nitrogen signaling. Identified putative cis-acting regulatory elements involved in mediating CN-responsive gene expression suggest multiple mechanisms for CN responsiveness. One mechanism invokes the existence of a single CN-responsive cis element, while another invokes the existence of cis elements that promote nitrogen-responsive gene expression only when present in combination with a carbon-responsive cis element. Conclusion: This study has allowed us to identify genes and processes regulated by interactions between carbon and nitrogen signaling and take a first step in uncovering how carbon- and nitrogen-signaling pathways interact to regulate transcription. Background Carbon and nitrogen are two major macronutrients required for plant growth and development. Specific carbon and nitro- gen metabolites act as signals to regulate the transcription of genes encoding enzymes involved in many essential proc- esses, including photosynthesis, carbon metabolism, Published: 29 October 2004 Genome Biology 2004, 5:R91 Received: 7 July 2004 Revised: 31 August 2004 Accepted: 23 September 2004 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2004/5/11/R91 R91.2 Genome Biology 2004, Volume 5, Issue 11, Article R91 Palenchar et al. http://genomebiology.com/2004/5/11/R91 Genome Genome Biology 2004, 5:359 comment reviews reports deposited research interactions information refereed research Meeting report Translational regulation of gene expression Stephanie Kervestin and Nadia Amrani Address: Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655-0122, USA. Correspondence: Nadia Amrani. E-mail: nadia.amrani@umassmed.edu Published: 25 November 2004 Genome Biology 2004, 5:359 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2004/5/12/359 © 2004 BioMed Central Ltd A report on the Cold Spring Harbor Laboratory meeting ‘Translational Control’, Cold Spring Harbor, USA, 7-12 September 2004. There have been major breakthroughs in recent years in understanding both the mechanism of mRNA translation and its control. High-resolution structures have revealed the ribosome’s role in the decoding process and the ribozyme activity of its peptidyl transferase center. The importance of post-transcriptional mechanisms in the regulation of gene expression is also much better appreciated today. The 2004 Cold Spring Harbor ‘Translational Control’ meeting addressed a variety of these mechanisms and provided new insights into the regulatory roles of RNA elements and RNA- binding protein complexes. Ribosomal structure and the mechanism of translation The crystal structures of ribosomes published in the past few years have revolutionized our understanding of the struc- tural basis of tRNA selection and the peptide-bond-forming activity of the ribosome. The precise mechanisms of the dis- tinct steps of protein synthesis are still unknown, however. This issue was addressed by several speakers, including Venki Ramakrishnan (MRC Laboratory of Molecular Biology, Cambridge, UK), who presented his recent work showing that the ribosome promotes accurate tRNA selec- tion at the ribosomal A site and that recognition of cognate codon-anticodon interaction induces the 30S ribosome subunit to adopt a closed conformation. This movement most probably accelerates the rate of GTP hydrolysis and the following accommodation step, observed by other groups from kinetic analysis. Other presentations focused on struc- tural rearrangements of the ribosome during elongation and translocation and, together, these structural data highlighted the dynamic nature of ribosome structure during the differ- ent steps of translation and prompted the audience to ponder which conformational changes are rate-limiting during translation. Structural analysis of the eukaryotic ribosome when associ- ated with translation factors has also brought new insights. In eukaryotes, initiation of translation is generally depen- dent on the presence of a 5Ј cap structure on the messenger RNA. Cap-dependent translation initiation is a complex process, facilitated by a large number of initiation factors (eIFs) that form a complicated network of cooperative inter- actions with the 40S ribosomal subunit. John McCarthy (Manchester Interdisciplinary Biocentre, UK) reported cryo- electron microscopy (cryo-EM) reconstructions, which indi- cate that binding of eIF1A to the 40S ribosomal subunit induces significant conformational changes in the subunit. These movements may create a recruitment-competent state of the 40S subunit that mediates the cooperative binding of other eIFs to form the 43S initiation complex. Moreover, the structure of the 43S complex indicates that the 40S to 43S transition involves a large rotation of the head of the small subunit; this is thought to reflect the opening of the mRNA channel which, in turn, may facilitate mRNA binding and subsequent scanning. The cap-independent pathway of translation initiation, uti- lized by both viral and cellular mRNAs, exploits highly struc- tured translation-initiation regions on mRNAs dubbed internal ribosome entry sites (IRESs). The IRES from the cricket paralysis virus (CrPV) directly assembles ... summarized in [link] The regulation of gene expression is discussed in detail in subsequent modules 2/5 Regulation of Gene Expression Differences in the Regulation of Gene Expression of Prokaryotic and... Evolution of Gene RegulationProkaryotic cells can only regulate gene expression by controlling the amount of transcription As eukaryotic cells evolved, the complexity of the control of gene expression. .. express a subset of the DNA that is encoded in any given cell In each cell type, the type and amount of 3/5 Regulation of Gene Expression protein is regulated by controlling gene expression To express