ChIP-seq and In Vivo Transcriptome Analyses of the Aspergillus fumigatus SREBP SrbA Reveals a New Regulator of the Fungal Hypoxia Response and Virulence

PLoS Pathogens

Volumn 10, Issue 11, 2014, Pages

  Chung, Dawoon ^a   Barker, Bridget M ^b,f   Carey, Charles C ^b   Merriman, Brittney ^b   Werner, Ernst R ^c   Lechner, Beatrix E ^c   Dhingra, Sourabh ^a   Cheng, Chao ^a   Xu, Wenjie ^d   Blosser, Sara J ^b   Morohashi, Kengo ^e   Mazurie, Aurélien ^b   Mitchell, Thomas K ^e   Haas, Hubertus ^c   Mitchell, Aaron P ^d   Cramer, Robert A ^a  

^a DARTMOUTH MEDICAL SCHOOL   (United States)

^b MONTANA STATE UNIVERSITY   (United States)

^c INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^d CARNEGIE MELLON UNIVERSITY   (United States)

^e OHIO STATE UNIVERSITY   (United States)

^f NORTHERN ARIZONA UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR; STEROL REGULATORY ELEMENT BINDING PROTEIN; FUNGAL PROTEIN; TRANSCRIPTOME;

AMINO ACID SEQUENCE; ANTIFUNGAL RESISTANCE; ARTICLE; ASPERGILLUS FUMIGATUS; CARBOHYDRATE METABOLISM; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; DNA SEQUENCE; GENE CONTROL; GENE EXPRESSION; GENE TARGETING; GENETIC TRANSCRIPTION; HYPOXIA; IRON TRANSPORT; LIPID METABOLISM; LUNG ASPERGILLOSIS; NONHUMAN; POLYMERASE CHAIN REACTION; SEQUENCE ALIGNMENT; SEQUENCE ANALYSIS; SEQUENCE HOMOLOGY; TRANSCRIPTOMICS; VIRULENCE; BIOSYNTHESIS; GENETICS; HIGH THROUGHPUT SEQUENCING; METABOLISM; PATHOGENICITY;

ASPERGILLUS FUMIGATUS;

ASPERGILLUS FUMIGATUS; FUNGAL PROTEINS; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; STEROL REGULATORY ELEMENT BINDING PROTEINS; TRANSCRIPTOME;

EID: 84912121231     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1004487     Document Type: Article

References (92)

1. Barron MA, Madinger NE, (2008) Opportunistic Fungal Infections, Part 2: Candida and Aspergillus. Infections in Medicine 25: 498–505.
2. Brown GD, Denning DW, Gow NA, Levitz SM, Netea MG, et al. (2012) Hidden killers: human fungal infections. Science translational medicine 4: 165rv113.
3. Brown GD, Denning DW, Levitz SM, (2012) Tackling human fungal infections. Science 336: 647.
4. Ben-Ami R, Lewis RE, Kontoyiannis DP, (2010) Enemy of the (immunosuppressed) state: an update on the pathogenesis of Aspergillus fumigatus infection. British Journal of Haematology 150: 406–417.
5. Steinbach WJ, (2013) Are We There Yet? Recent Progress in the Molecular Diagnosis and Novel Antifungal Targeting of Aspergillus fumigatus and Invasive Aspergillosis. PLoS Pathogens 9: e1003642.
6. Willger S, Grahl N, Cramer R, (2009) Aspergillus fumigatus metabolism: Clues to mechanisms of in vivo fungal growth and virulence. Medical Mycology 47: S72–S79.
7. Grahl N, Puttikamonkul S, Macdonald JM, Gamcsik MP, Ngo LY, et al. (2011) In vivo hypoxia and a fungal alcohol dehydrogenase influence the pathogenesis of invasive pulmonary aspergillosis. PLoS Pathogens 7: e1002145.
8. Tarrand JJ, Han XY, Kontoyiannis DP, May GS, (2005) Aspergillus hyphae in infected tissue: Evidence of physiologic adaptation and effect on culture recovery. Journal of Clinical Microbiology 43: 382–386.
9. Hall LA, Denning DW, (1994) Oxygen Requirements of Aspergillus Species. Journal of Medical Microbiology 41: 311–315.
10. Brock M, Jouvion G, Droin-Bergere S, Dussurget O, Nicola MA, et al. (2008) Bioluminescent Aspergillus fumigatus, a new tool for drug eficiency testing and in vivo monitoring of invasive aspergillosis. Applied and Environmental Microbiology 74: 7023–7035.
11. Brown JM, Wilson WR, (2004) Exploiting tumour hypoxia in cancer treatment. Nature reviews Cancer 4: 437–447.
12. Koeppen M, Eckle T, Eltzschig HK, (2011) The hypoxia-inflammation link and potential drug targets. Current opinion in anaesthesiology 24: 363–369.
13. Eltzschig HK, Carmeliet P, (2011) Hypoxia and inflammation. The New England Journal of Medicine 364: 656–665.
14. Moeller BJ, Richardson RA, Dewhirst MW, (2007) Hypoxia and radiotherapy: opportunities for improved outcomes in cancer treatment. Cancer Metastasis Reviews 26: 241–248.
15. Grahl N, Cramer RA, Jr (2010) Regulation of hypoxia adaptation: an overlooked virulence attribute of pathogenic fungi? Medical Mycology: Official Publication of the International Society for Human and Animal Mycology 48: 1–15.
16. Ernst JF, Tielker D, (2009) Responses to hypoxia in fungal pathogens. Cellular Microbiology 11: 183–190.
17. Hsu JL, Khan MA, Sobel RA, Jiang X, Clemons KV, et al. (2013) Aspergillus fumigatus invasion increases with progressive airway ischemia. PloS One 8: e77136.
18. Chun CD, Liu OW, Madhani HD, (2007) A link between virulence and homeostatic responses to hypoxia during infection by the human fungal pathogen Cryptococcus neoformans. PLoS Pathogens 3: e22.
19. Chang YC, Bien CM, Lee H, Espenshade PJ, Kwon-Chung KJ, (2007) Sre1p, a regulator of oxygen sensing and sterol homeostasis, is required for virulence in Cryptococcus neoformans. Molecular microbiology 64: 614–629.
20. Grahl N, Shepardson KM, Chung D, Cramer RA, (2012) Hypoxia and fungal pathogenesis: to air or not to air? Eukaryotic cell 11: 560–570.
21. Bien CM, Espenshade PJ, (2010) Sterol regulatory element binding proteins in fungi: hypoxic transcription factors linked to pathogenesis. Eukaryotic Cell 9: 352–359.
22. Hua X, Wu J, Goldstein JL, Brown MS, Hobbs HH, (1995) Structure of the human gene encoding sterol regulatory element binding protein-1 (SREBF1) and localization of SREBF1 and SREBF2 to chromosomes 17p11.2 and 22q13. Genomics 25: 667–673.
23. Horton JD, (2002) Sterol regulatory element-binding proteins: transcriptional activators of lipid synthesis. Biochemical Society transactions 30: 1091–1095.
24. Seo YK, Chong HK, Infante AM, Im SS, Xie X, et al. (2009) Genome-wide analysis of SREBP-1 binding in mouse liver chromatin reveals a preference for promoter proximal binding to a new motif. Proceedings of the National Academy of Sciences of the United States of America 106: 13765–13769.
25. Seo YK, Jeon TI, Chong HK, Biesinger J, Xie X, et al. (2011) Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy. Cell Metabolism 13: 367–375.
26. Reed BD, Charos AE, Szekely AM, Weissman SM, Snyder M, (2008) Genome-wide occupancy of SREBP1 and its partners NFY and SP1 reveals novel functional roles and combinatorial regulation of distinct classes of genes. PLoS Genetics 4: e1000133.
27. Hughes AL, Todd BL, Espenshade PJ, (2005) SREBP pathway responds to sterols and functions as an oxygen sensor in fission yeast. Cell 120: 831–842.
28. Todd BL, Stewart EV, Burg JS, Hughes AL, Espenshade PJ, (2006) Sterol regulatory element binding protein is a principal regulator of anaerobic gene expression in fission yeast. Molecular and Cellular Biology 26: 2817–2831.
29. Porter JR, Burg JS, Espenshade PJ, Iglesias PA, (2010) Ergosterol regulates sterol regulatory element binding protein (SREBP) cleavage in fission yeast. The Journal of Biological Chemistry 285: 41051–41061.
30. Lloyd SJ, Raychaudhuri S, Espenshade PJ, (2013) Subunit architecture of the Golgi Dsc E3 ligase required for sterol regulatory element-binding protein (SREBP) cleavage in fission yeast. The Journal of Biological Chemistry 288: 21043–21054.
31. Cheung R, Espenshade PJ, (2013) Structural requirements for sterol regulatory element-binding protein (SREBP) cleavage in fission yeast. The Journal of Biological Chemistry 288: 20351–20360.
32. Porter JR, Lee CY, Espenshade PJ, Iglesias PA, (2012) Regulation of SREBP during hypoxia requires Ofd1-mediated control of both DNA binding and degradation. Molecular Biology of the Cell 23: 3764–3774.
33. Stewart EV, Lloyd SJ, Burg JS, Nwosu CC, Lintner RE, et al. (2012) Yeast sterol regulatory element-binding protein (SREBP) cleavage requires Cdc48 and Dsc5, a ubiquitin regulatory X domain-containing subunit of the Golgi Dsc E3 ligase. The Journal of Biological Chemistry 287: 672–681.
34. Hughes BT, Nwosu CC, Espenshade PJ, (2009) Degradation of sterol regulatory element-binding protein precursor requires the endoplasmic reticulum-associated degradation components Ubc7 and Hrd1 in fission yeast. The Journal of Biological Chemistry 284: 20512–20521.
35. Hughes BT, Espenshade PJ, (2008) Oxygen-regulated degradation of fission yeast SREBP by Ofd1, a prolyl hydroxylase family member. The EMBO Journal 27: 1491–1501.
36. Willger SD, Puttikamonkul S, Kim KH, Burritt JB, Grahl N, et al. (2008) A sterol-regulatory element binding protein is required for cell polarity, hypoxia adaptation, azole drug resistance, and virulence in Aspergillus fumigatus. PLoS Pathogens 4: e1000200.
37. Willger SD, Cornish EJ, Chung D, Fleming BA, Lehmann MM, et al. (2012) Dsc orthologs are required for hypoxia adaptation, triazole drug responses, and fungal virulence in Aspergillus fumigatus. Eukaryotic Cell 11: 1557–1567.
38. Blatzer M, Barker BM, Willger SD, Beckmann N, Blosser SJ, et al. (2011) SREBP coordinates iron and ergosterol homeostasis to mediate triazole drug and hypoxia responses in the human fungal pathogen Aspergillus fumigatus. PLoS Genetics 7: e1002374.
39. Chang YC, Ingavale SS, Bien C, Espenshade P, Kwon-Chung KJ, (2009) Conservation of the sterol regulatory element-binding protein pathway and its pathobiological importance in Cryptococcus neoformans. Eukaryotic Cell 8: 1770–1779.
40. Barker BM, Kroll K, Vodisch M, Mazurie A, Kniemeyer O, et al. (2012) Transcriptomic and proteomic analyses of the Aspergillus fumigatus hypoxia response using an oxygen-controlled fermenter. BMC genomics 13: 62.
41. Butler G, (2013) Hypoxia and gene expression in eukaryotic microbes. Annual Review of Microbiology 67: 291–312.
42. Sailsbery JK, Atchley WR, Dean RA, (2012) Phylogenetic analysis and classification of the fungal bHLH domain. Molecular Biology and Evolution 29: 1301–1318.
43. Davies BS, Rine J, (2006) A role for sterol levels in oxygen sensing in Saccharomyces cerevisiae. Genetics 174: 191–201.
44. Losada L, Barker BM, Pakala S, Joardar V, Zafar N, et al. (2014) Large-scale transcriptional response to hypoxia in Aspergillus fumigatus observed using RNAseq identifies a novel hypoxia regulated ncRNA. Mycopathologia [Epub ahead of print].
45. Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, et al. (2008) Model-based analysis of ChIP-Seq (MACS). Genome Biology 9: R137.
46. Grant CE, Bailey TL, Noble WS, (2011) FIMO: scanning for occurrences of a given motif. Bioinformatics 27: 1017–1018.
47. Linde J, Hortschansky P, Fazius E, Brakhage AA, Guthke R, et al. (2012) Regulatory interactions for iron homeostasis in Aspergillus fumigatus inferred by a Systems Biology approach. BMC Systems Biology 6: 6.
48. Yokoyama C, Wang X, Briggs MR, Admon A, Wu J, et al. (1993) SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene. Cell 75: 187–197.
49. Kim JB, Spotts GD, Halvorsen YD, Shih HM, Ellenberger T, et al. (1995) Dual DNA binding specificity of ADD1/SREBP1 controlled by a single amino acid in the basic helix-loop-helix domain. Molecular and Cellular Biology 15: 2582–2588.
50. Perez JC, Kumamoto CA, Johnson AD, (2013) Candida albicans commensalism and pathogenicity are intertwined traits directed by a tightly knit transcriptional regulatory circuit. PLoS Biology 11: e1001510.
51. Priebe S, Linde J, Albrecht D, Guthke R, Brakhage AA, (2011) FungiFun: a web-based application for functional categorization of fungal genes and proteins. Fungal Genetics and Biology 48: 353–358.
52. Geiss GK, Bumgarner RE, Birditt B, Dahl T, Dowidar N, et al. (2008) Direct multiplexed measurement of gene expression with color-coded probe pairs. Nature Biotechnology 26: 317–325.
53. Malkov VA, Serikawa KA, Balantac N, Watters J, Geiss G, et al. (2009) Multiplexed measurements of gene signatures in different analytes using the Nanostring nCounter Assay System. BMC Research Notes 2: 80.
54. Schrettl M, Kim HS, Eisendle M, Kragl C, Nierman WC, et al. (2008) SreA-mediated iron regulation in Aspergillus fumigatus. Molecular Microbiology 70: 27–43.
55. Znaidi S, Nesseir A, Chauvel M, Rossignol T, d'Enfert C, (2013) A comprehensive functional portrait of two heat shock factor-type transcriptional regulators involved in Candida albicans morphogenesis and virulence. PLoS Pathogens 9: e1003519.
56. Zagorec M, Buhler JM, Treich I, Keng T, Guarente L, et al. (1988) Isolation, sequence, and regulation by oxygen of the yeast HEM13 gene coding for coproporphyrinogen oxidase. The Journal of Biological Chemistry 263: 9718–9724.
57. Keng T, (1992) HAP1 and ROX1 form a regulatory pathway in the repression of HEM13 transcription in Saccharomyces cerevisiae. Molecular and Cellular Biology 12: 2616–2623.
58. Soriani FM, Malavazi I, Ferreira MED, Savoldi M, Kress MRV, et al. (2008) Functional characterization of the Aspergillus fumigatus CRZ1 homologue, CrzA. Molecular Microbiology 67: 1274–1291.
59. Blosser SJ, Merriman B, Grahl N, Chung D, Cramer RA, (2014) Two C4-sterol methyl oxidases (Erg25) catalyze ergosterol intermediate demethylation and impact environmental stress adaptation in Aspergillus fumigatus. Microbiology DOI: 10.1099/mic.0.080440-0
60. Zhou S, Fushinobu S, Kim SW, Nakanishi Y, Maruyama J, et al. (2011) Functional analysis and subcellular location of two flavohemoglobins from Aspergillus oryzae. Fungal Genetics and Biology 48: 200–207.
61. Li H, Barker BM, Grahl N, Puttikamonkul S, Bell JD, et al. (2011) The small GTPase RacA mediates intracellular reactive oxygen species production, polarized growth, and virulence in the human fungal pathogen Aspergillus fumigatus. Eukaryotic Cell 10: 174–186.
62. Borneman AR, Gianoulis TA, Zhang ZD, Yu H, Rozowsky J, et al. (2007) Divergence of transcription factor binding sites across related yeast species. Science 317: 815–819.
63. Odom DT, Dowell RD, Jacobsen ES, Gordon W, Danford TW, et al. (2007) Tissue-specific transcriptional regulation has diverged significantly between human and mouse. Nature Genetics 39: 730–732.
64. Schmidt D, Wilson MD, Ballester B, Schwalie PC, Brown GD, et al. (2010) Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science 328: 1036–1040.
65. Tuch BB, Galgoczy DJ, Hernday AD, Li H, Johnson AD, (2008) The evolution of combinatorial gene regulation in fungi. PLoS Biology 6: e38.
66. Hughes TR, de Boer CG, (2013) Mapping yeast transcriptional networks. Genetics 195: 9–36.
67. Zitomer RS, Lowry CV, (1992) Regulation of gene expression by oxygen in Saccharomyces cerevisiae. Microbiological Reviews 56: 1–11.
68. Hon T, Dodd A, Dirmeier R, Gorman N, Sinclair PR, et al. (2003) A mechanism of oxygen sensing in yeast. Multiple oxygen-responsive steps in the heme biosynthetic pathway affect Hap1 activity. The Journal of Biological Chemistry 278: 50771–50780.
69. Hickman MJ, Winston F, (2007) Heme levels switch the function of Hap1 of Saccharomyces cerevisiae between transcriptional activator and transcriptional repressor. Molecular and Cellular Biology 27: 7414–7424.
70. Thorsness M, Schafer W, D'Ari L, Rine J, (1989) Positive and negative transcriptional control by heme of genes encoding 3-hydroxy-3-methylglutaryl coenzyme A reductase in Saccharomyces cerevisiae. Molecular and Cellular Biology 9: 5702–5712.
71. Jin FJ, Takahashi T, Matsushima K, Hara S, Shinohara Y, et al. (2011) SclR, a basic helix-loop-helix transcription factor, regulates hyphal morphology and promotes sclerotial formation in Aspergillus oryzae. Eukaryotic cell 10: 945–955.
72. Rosenbach A, Dignard D, Pierce JV, Whiteway M, Kumamoto CA, (2010) Adaptations of Candida albicans for growth in the mammalian intestinal tract. Eukaryotic Cell 9: 1075–1086.
73. Nobile CJ, Fox EP, Nett JE, Sorrells TR, Mitrovich QM, et al. (2012) A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell 148: 126–138.
74. Nett JE, Lepak AJ, Marchillo K, Andes DR, (2009) Time course global gene expression analysis of an in vivo Candida biofilm. The Journal of Infectious Diseases 200: 307–313.
75. Lane S, Zhou S, Pan T, Dai Q, Liu H, (2001) The basic helix-loop-helix transcription factor Cph2 regulates hyphal development in Candida albicans partly via TEC1. Molecular and Biology 21: 6418–6428.
76. Sellam A, van het Hoog M, Tebbji F, Beaurepaire C, Whiteway M, et al. (2014) Modeling the transcriptional regulatory network that controls the early hypoxic response in Candida albicans. Eukaryot Cell 13: 675–690.
77. Datta S, Osborne TF, (2005) Activation domains from both monomers contribute to transcriptional stimulation by sterol regulatory element-binding protein dimers. The Journal of Biological Chemistry 280: 3338–3345.
78. Zoumi A, Datta S, Liaw LH, Wu CJ, Manthripragada G, et al. (2005) Spatial distribution and function of sterol regulatory element-binding protein 1a and 2 homo- and heterodimers by in vivo two-photon imaging and spectroscopy fluorescence resonance energy transfer. Molecular and Cellular Biology 25: 2946–2956.
79. Robinson KA, Lopes JM, (2000) SURVEY AND SUMMARY: Saccharomyces cerevisiae basic helix-loop-helix proteins regulate diverse biological processes. Nucleic Acids Research 28: 1499–1505.
80. Shao W, Espenshade PJ, (2012) Expanding roles for SREBP in metabolism. Cell Metabolism 16: 414–419.
81. Shimizu K, Keller NP, (2001) Genetic involvement of a cAMP-dependent protein kinase in a g protein signaling pathway regulating morphological and chemical transitions in Aspergillus nidulans. Genetics 157: 591–600.
82. Yu JH, Hamari Z, Han KH, Seo JA, Reyes-Dominguez Y, et al. (2004) Double-joint PCR: a PCR-based molecular tool for gene manipulations in filamentous fungi. Fungal genetics and biology 41: 973–981.
83. Quail MA, Kozarewa I, Smith F, Scally A, Stephens PJ, et al. (2008) A large genome center's improvements to the Illumina sequencing system. Nature Methods 5: 1005–1010.
84. Lohse M, Bolger AM, Nagel A, Fernie AR, Lunn JE, et al. (2012) RobiNA: a user-friendly, integrated software solution for RNA-Seq-based transcriptomics. Nucleic Acids Research 40: W622–627.
85. Langmead B, Trapnell C, Pop M, Salzberg SL, (2009) Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biology 10: R25.
86. Bailey TL, Elkan C, (1994) Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proceedings/International Conference on Intelligent Systems for Molecular Biology; ISMB International Conference on Intelligent Systems for Molecular Biology 2: 28–36.
87. Carlson JM, Chakravarty A, DeZiel CE, Gross RH, (2007) SCOPE: a web server for practical de novo motif discovery. Nucleic Acids Research 35: W259–264.
88. Pavesi G, Mereghetti P, Mauri G, Pesole G, (2004) Weeder Web: discovery of transcription factor binding sites in a set of sequences from co-regulated genes. Nucleic Acids Research 32: W199–203.
89. Roberts A, Trapnell C, Donaghey J, Rinn JL, Pachter L, (2011) Improving RNA-Seq expression estimates by correcting for fragment bias. Genome Biology 12: R22.
90. Kim D, Pertea G, Trapnell C, Pimentel H, Kelley R, et al. (2013) TopHat2: accurate alignment of transcriptomes in the presence of insertions, deletions and gene fusions. Genome Biology 14: R36.
91. RDevelopmentCoreTeam (2011) R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing.
92. Bonkovsky HL, Wood SG, Howell SK, Sinclair PR, Lincoln B, et al. (1986) High-performance liquid chromatographic separation and quantitation of tetrapyrroles from biological materials. Anal Biochem 155: 56–64.