期刊论文详细信息
BioData Mining
Detection of changes in gene regulatory patterns, elicited by perturbations of the Hsp90 molecular chaperone complex, by visualizing multiple experiments with an animation
Pablo C Echeverría1  Fedor Forafonov1  Deo P Pandey2  Guillaume Mühlebach1  Didier Picard1 
[1] Département de Biologie Cellulaire, Université de Genève, Sciences 3, CH - 1211 Genève 4, Switzerland
[2] Biotech Research and Innovation Center (BRIC), University of Copenhagen, Ole Maaloes vej 5, 2200 Copenhagen, Denmark
关键词: gene deletion;    inhibitor;    Hsp90;    molecular chaperones;    stress response;    yeast;    visualization;    microarray analysis;    gene expression;   
Others  :  797343
DOI  :  10.1186/1756-0381-4-15
 received in 2011-03-08, accepted in 2011-06-14,  发布年份 2011
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【 摘 要 】

Background

To make sense out of gene expression profiles, such analyses must be pushed beyond the mere listing of affected genes. For example, if a group of genes persistently display similar changes in expression levels under particular experimental conditions, and the proteins encoded by these genes interact and function in the same cellular compartments, this could be taken as very strong indicators for co-regulated protein complexes. One of the key requirements is having appropriate tools to detect such regulatory patterns.

Results

We have analyzed the global adaptations in gene expression patterns in the budding yeast when the Hsp90 molecular chaperone complex is perturbed either pharmacologically or genetically. We integrated these results with publicly accessible expression, protein-protein interaction and intracellular localization data. But most importantly, all experimental conditions were simultaneously and dynamically visualized with an animation. This critically facilitated the detection of patterns of gene expression changes that suggested underlying regulatory networks that a standard analysis by pairwise comparison and clustering could not have revealed.

Conclusions

The results of the animation-assisted detection of changes in gene regulatory patterns make predictions about the potential roles of Hsp90 and its co-chaperone p23 in regulating whole sets of genes. The simultaneous dynamic visualization of microarray experiments, represented in networks built by integrating one's own experimental with publicly accessible data, represents a powerful discovery tool that allows the generation of new interpretations and hypotheses.

【 授权许可】

   
2011 Echeverría et al; licensee BioMed Central Ltd.

【 预 览 】
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Figure 5. 64KB Image download
Figure 4. 76KB Image download
Figure 3. 68KB Image download
Figure 2. 295KB Image download
Figure 1. 57KB Image download
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【 参考文献 】
  • [1]Ideker T, Ozier O, Schwikowski B, Siegel AF: Discovering regulatory and signalling circuits in molecular interaction networks. Bioinformatics 2002, 18(Suppl. 1):S233-240.
  • [2]Ulitsky I, Shamir R: Identification of functional modules using network topology and high-throughput data. BMC Syst Biol 2007, 1:8. BioMed Central Full Text
  • [3]Bernthaler A, Muhlberger I, Fechete R, Perco P, Lukas A, Mayer B: A dependency graph approach for the analysis of differential gene expression profiles. Mol Biosyst 2009, 5:1720-1731.
  • [4]Adler P, Reimand J, Janes J, Kolde R, Peterson H, Vilo J: KEGGanim: pathway animations for high-throughput data. Bioinformatics 2008, 24:588-590.
  • [5]Gehlenborg N, O'Donoghue SI, Baliga NS, Goesmann A, Hibbs MA, Kitano H, Kohlbacher O, Neuweger H, Schneider R, Tenenbaum D, Gavin AC: Visualization of omics data for systems biology. Nat Methods 2010, 7:S56-68.
  • [6]Fox P, Hendler J: Changing the equation on scientific data visualization. Science 2011, 331:705-708.
  • [7]Wong B: Points of View: Gestalt principles (Part 2). Nat Methods 2010, 7:941-941.
  • [8]Picard D: Heat-shock protein 90, a chaperone for folding and regulation. Cell Mol Life Sci 2002, 59:1640-1648.
  • [9]Caplan AJ: What is a co-chaperone? Cell Stress Chaperones 2003, 8:105-107.
  • [10]McLaughlin SH, Sobott F, Yao ZP, Zhang W, Nielsen PR, Grossmann JG, Laue ED, Robinson CV, Jackson SE: The co-chaperone p23 arrests the Hsp90 ATPase cycle to trap client proteins. J Mol Biol 2006, 356:746-758.
  • [11]Johnson JL, Beito TG, Krco CJ, Toft DO: Characterization of a novel 23-kilodalton protein of unactive progesterone receptor complexes. Mol Cell Biol 1994, 14:1956-1963.
  • [12]Felts SJ, Toft DO: p23, a simple protein with complex activities. Cell Stress Chaperones 2003, 8:108-113.
  • [13]Weaver AJ, Sullivan WP, Felts SJ, Owen BA, Toft DO: Crystal structure and activity of human p23, a heat shock protein 90 co-chaperone. J Biol Chem 2000, 275:23045-23052.
  • [14]Ali MM, Roe SM, Vaughan CK, Meyer P, Panaretou B, Piper PW, Prodromou C, Pearl LH: Crystal structure of an Hsp90-nucleotide-p23/Sba1 closed chaperone complex. Nature 2006, 440:1013-1017.
  • [15]Richter K, Walter S, Buchner J: The co-chaperone Sba1 connects the ATPase reaction of Hsp90 to the progression of the chaperone cycle. J Mol Biol 2004, 342:1403-1413.
  • [16]Sullivan WP, Owen BA, Toft DO: The influence of ATP and p23 on the conformation of hsp90. J Biol Chem 2002, 277:45942-45948.
  • [17]Johnson JL, Toft DO: Binding of p23 and hsp90 during assembly with the progesterone receptor. Mol Endocrinol 1995, 9:670-678.
  • [18]Kovacs JJ, Murphy PJ, Gaillard S, Zhao X, Wu JT, Nicchitta CV, Yoshida M, Toft DO, Pratt WB, Yao TP: HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell 2005, 18:601-607.
  • [19]Bohen SP: Genetic and biochemical analysis of p23 and ansamycin antibiotics in the function of Hsp90-dependent signaling proteins. Mol Cell Biol 1998, 18:3330-3339.
  • [20]Grad I, McKee TA, Ludwig SM, Hoyle GW, Ruiz P, Wurst W, Floss T, Miller CA III, Picard D: The Hsp90 co-chaperone p23 is essential for perinatal survival. Mol Cell Biol 2006, 26:8976-8983.
  • [21]Forafonov F, Toogun OA, Grad I, Suslova E, Freeman BC, Picard D: p23/Sba1p protects against Hsp90 inhibitors independently of its intrinsic chaperone activity. Mol Cell Biol 2008, 28:3446-3456.
  • [22]Pandey DP, Lappano R, Albanito L, Madeo A, Maggiolini M, Picard D: Estrogenic GPR30 signalling induces proliferation and migration of breast cancer cells through CTGF. EMBO J 2009, 28:523-532.
  • [23]Kralli A, Bohen SP, Yamamoto KR: LEM1, an ATP-binding-cassette transporter, selectively modulates the biological potency of steroid hormones. Proc Natl Acad Sci USA 1995, 92:4701-4705.
  • [24]Stanhill A, Schick N, Engelberg D: The yeast ras/cyclic AMP pathway induces invasive growth by suppressing the cellular stress response. Mol Cell Biol 1999, 19:7529-7538.
  • [25]Louvion JF, Havaux-Copf B, Picard D: Fusion of GAL4-VP16 to a steroid binding domain provides a tool for gratuitous induction of galactose-responsive genes in yeast. Gene 1993, 131:129-134.
  • [26]Cline MS, Smoot M, Cerami E, Kuchinsky A, Landys N, Workman C, Christmas R, Avila-Campilo I, Creech M, Gross B, Hanspers K, Isserlin R, Kelley R, Killcoyne S, Lotia S, Maere S, Morris J, Ono K, Pavlovic V, Pico AR, Vailaya A, Wang PL, Adler A, Conklin BR, Hood L, Kuiper M, Sander C, Schmulevich I, Schwikowski B, Warner GJ, Ideker T, Bader GD: Integration of biological networks and gene expression data using Cytoscape. Nat Protoc 2007, 2:2366-2382.
  • [27]Barsky A, Gardy JL, Hancock RE, Munzner T: Cerebral: a Cytoscape plugin for layout of and interaction with biological networks using subcellular localization annotation. Bioinformatics 2007, 23:1040-1042.
  • [28]Ki SW, Ishigami K, Kitahara T, Kasahara K, Yoshida M, Horinouchi S: Radicicol binds and inhibits mammalian ATP citrate lyase. J Biol Chem 2000, 275:39231-39236.
  • [29]Besant PG, Lasker MV, Bui CD, Turck CW: Inhibition of branched-chain α-keto acid dehydrogenase kinase and Sln1 yeast histidine kinase by the antifungal antibiotic radicicol. Mol Pharmacol 2002, 62:289-296.
  • [30]Gadelle D, Bocs C, Graille M, Forterre P: Inhibition of archaeal growth and DNA topoisomerase VI activities by the Hsp90 inhibitor radicicol. Nucleic Acids Res 2005, 33:2310-2317.
  • [31]Breitkreutz BJ, Stark C, Reguly T, Boucher L, Breitkreutz A, Livstone M, Oughtred R, Lackner DH, Bahler J, Wood V, Dolinski K, Tyers M: The BioGRID Interaction Database: 2008 update. Nucleic Acids Res 2008, 36:D637-640.
  • [32]Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G: Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 2000, 25:25-29.
  • [33]Wandinger SK, Suhre MH, Wegele H, Buchner J: The phosphatase Ppt1 is a dedicated regulator of the molecular chaperone Hsp90. EMBO J 2006, 25:367-376.
  • [34]Estruch F: Stress-controlled transcription factors, stress-induced genes and stress tolerance in budding yeast. FEMS Microbiol Rev 2000, 24:469-486.
  • [35]Martinez-Pastor MT, Marchler G, Schuller C, Marchler-Bauer A, Ruis H, Estruch F: The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). EMBO J 1996, 15:2227-2235.
  • [36]Boy-Marcotte E, Lagniel G, Perrot M, Bussereau F, Boudsocq A, Jacquet M, Labarre J: The heat shock response in yeast: differential regulations and contributions of the Msn2p/Msn4p and Hsf1p regulons. Mol Microbiol 1999, 33:274-283.
  • [37]Ferguson SB, Anderson ES, Harshaw RB, Thate T, Craig NL, Nelson HC: Protein kinase A regulates constitutive expression of small heat-shock genes in an Msn2/4p-independent and Hsf1p-dependent manner in Saccharomyces cerevisiae. Genetics 2005, 169:1203-1214.
  • [38]Ptacek J, Devgan G, Michaud G, Zhu H, Zhu X, Fasolo J, Guo H, Jona G, Breitkreutz A, Sopko R, McCartney RR, Schmidt MC, Rachidi N, Lee SJ, Mah AS, Meng L, Stark MJ, Stern DF, De Virgilio C, Tyers M, Andrews B, Gerstein M, Schweitzer B, Predki PF, Snyder M: Global analysis of protein phosphorylation in yeast. Nature 2005, 438:679-684.
  • [39]Mandal AK, Lee P, Chen JA, Nillegoda N, Heller A, DiStasio S, Oen H, Victor J, Nair DM, Brodsky JL, Caplan AJ: Cdc37 has distinct roles in protein kinase quality control that protect nascent chains from degradation and promote posttranslational maturation. J Cell Biol 2007, 176:319-328.
  • [40]Geymonat M, Wang L, Garreau H, Jacquet M: Ssa1p chaperone interacts with the guanine nucleotide exchange factor of ras Cdc25p and controls the cAMP pathway in Saccharomyces cerevisiae. Mol Microbiol 1998, 30:855-864.
  • [41]Thevelein JM, de Winde JH: Novel sensing mechanisms and targets for the cAMP-protein kinase A pathway in the yeast Saccharomyces cerevisiae. Mol Microbiol 1999, 33:904-918.
  • [42]Zarzov P, Boucherie H, Mann C: A yeast heat shock transcription factor (Hsf1) mutant is defective in both Hsc82/Hsp82 synthesis and spindle pole body duplication. J Cell Sci 1997, 110:1879-1891.
  • [43]Erkine AM, Adams CC, Gao M, Gross DS: Multiple protein-DNA interactions over the yeast HSC82 heat shock gene promoter. Nucleic Acids Res 1995, 23:1822-1829.
  • [44]Duina AA, Kalton HM, Gaber RF: Requirement for Hsp90 and a CyP-40-type cyclophilin in negative regulation of the heat shock response. J Biol Chem 1998, 273:18974-18978.
  • [45]Stavreva DA, Wiench M, John S, Conway-Campbell BL, McKenna MA, Pooley JR, Johnson TA, Voss TC, Lightman SL, Hager GL: Ultradian hormone stimulation induces glucocorticoid receptor-mediated pulses of gene transcription. Nat Cell Biol 2009, 11:1093-1102.
  • [46]Toogun OA, Dezwaan DC, Freeman BC: The hsp90 molecular chaperone modulates multiple telomerase activities. Mol Cell Biol 2008, 28:457-467.
  • [47]Echeverría PC, Picard D: Molecular chaperones, essential partners of steroid hormone receptors for activity and mobility. Biochim Biophys Acta 2010, 1803:641-649.
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