Analysis of coexpressed genes in response to different perturbations at the genome-level can provide new insight into global regulatory structures. Here we performed integrated data analysis for a crossspecies comparative investigation by exploring genomes and transcriptional coexpression profiles in Aspergillus oryzae and Aspergillus niger. Based on our analysis of conserved coexpressed genes, fatty acid catabolism via beta-oxidation, fatty acid transport, the glyoxylate bypass, and peroxisomal biogenesis were identified as core coevolved pathways between the two species. The occurrence of coexpression patterns, allowed for identification of DNA regulatory motifs and putative corresponding transcription factors, and we hereby show that comparative transcriptome analysis between two closely related fungi allows for identification of how genes involved in the utilization of fatty acids, peroxisomal biogenesis, and the glyoxylate bypass are regulated. Interestingly, “CCTCGG” was identified as a core binding site for the putative FarA and FarB transcription factors that govern the underlined biological processes. Phylogeny and domain architecture analysis of amino acid sequences of FarA and FarB in eight species of aspergilli, clearly indicate that these proteins are evolutionarily conserved across Aspergillus species as well as they are conserved in other fungi.
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References
1.
AlterO., BrownP.O., BotsteinD.2000. Singular value decomposition for genome-wide expression data processing and modeling. Proc Natl Acad Sci USA, 97:10101–10106.
AndersenM.R., NielsenM.L., NielsenJ.2008a. Metabolic model integration of the bibliome, genome, metabolome and reactome of Aspergillus niger. Mol Syst Biol, 4:178.
5.
AndersenM.R., VongsangnakW., PanagiotouG., MargaritaP.S., LehmannL., NielsenJ.2008b. A tri-species Aspergillus microarray—advancing comparative transcriptomics. Proc Natl Acad Sci USA, 105:4387–4392.
6.
BembomO., KelesS., van der LaanM.2007. Supervised detection of conserved motifs in DNA sequences with cosmo. Stat Appl Genet Mol Biol, 6Article 8.
7.
BrazmaA., JonassenI., ViloJ., UkkonenE.1998. Predicting gene regulatory elements in silico on a genomic scale. Genome Res, 8:1202–1215.
8.
BrentR.2000. Genomic biology. Cell, 100:169–183.
9.
Chamalaun-HusseyN.1996. Characterization of DNA-binding by the CreA protein of Aspergillus nidulans. PhD thesis, The university of Adelaide: Department of Genetics.
10.
DavidH., HofmannG., OliveiraA.P., JarmerH., NielsenJ.2006. Metabolic network driven analysis of genome-wide transcription data from Aspergillus nidulans. Genome Biol, 7.
11.
DowzerC.E., KellyJ.M.1989. Cloning of the creA gene from Aspergillus nidulans: a gene involved in carbon catabolite repression. Curr Genet, 15:457–459.
12.
DowzerC.E., KellyJ.M.1991. Analysis of the creA gene, a regulator of carbon catabolite repression in Aspergillus nidulans. Mol Cell Biol, 11:5701–5709.
13.
DudoitS., GendemanR.C., QuackenbushJ.2003. Open source software for the analysis of microarray data. Biotechniques Suppl, 45–51.
14.
FedorovaN., KhaldiN., JoardarV., MaitiR., AmedeoP., AndersonM.J.et al.2008. Genomic islands in the pathogenic filamentous fungus Aspergillus fumigatus. PLoS Genet, 4.
15.
FelsensteinJ.1985. Confidence limits on phylogenies: an approach using the bootstrap. Evolution, 39:783–791.
16.
GalaganJ.E., CalvoS.E., CuomoC., MaL., WortmanJ.R., BatzoglouS.et al.2005. Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae. Nature, 438:1105–1115.
17.
GautierL., CopeL., BolstadB.M., IrizarryR.A.2004. affy—analysis of Affymetrix GeneChip data at the probe level. Bioinformatics, 20:307–315.
18.
GentlemanR.C., CareyV.J., BatesD.M., BolstadB., DettlingM., DudoitS.et al.2004. Bioconductor: open software development for computational biology and bioinformatics. Genome Biol, 5.
19.
GielkensM.M., DekkersE., VisserJ., de GraaffL.H.1999. Two cellobiohydrolase-encoding genes from Aspergillus niger require D-xylose and the xylanolytic transcriptional activator XlnR for their expression. Appl Environ Microbiol, 65:4340–4345.
20.
GrotkjaerT., WintherO., RegenbergB., NielsenJ., HansenL. K.2006. Robust multi-scale clustering of large DNA microarray datasets with the consensus algorithm. Bioinformatics, 22:58–67.
21.
HieterP., BoguskiM.1997. Functional genomics: it's all how you read it. Science, 278:601–602.
22.
HynesM.J., MurrayS.L., DuncanA., KhewG.S., DavisM.A.2006. Regulatory genes controlling fatty acid catabolism and peroxisomal functions in the filamentous fungus Aspergillus nidulans. Eukaryotic Cell, 5:794–805.
23.
KielJ., van der KleiI.J.2009. Proteins involved in microbody biogenesis and degradation in Aspergillus nidulans. Fungal Genet Biol, 46:S62–S71.
24.
MachidaM., AsaiK., SanoM., TanakaT., KumagaiT., TeraiG.et al.2005. Genome sequencing and analysis of Aspergillus oryzae. Nature, 438:1157–1161.
25.
MaruiJ., KitamotoN., KatoM., KobayashiT., TsukagoshiN.2002a. Transcriptional activator, AoXlnR, mediates cellulose-inductive expression of the xylanolytic and cellulolytic genes in Aspergillus oryzae. FEBS Lett, 528:279–282.
26.
MaruiJ., TanakaA., MimuraS., de GraaffL.H., VisserJ., KitamotoN.et al.2002b. A transcriptional activator, AoXlnR, controls the expression of genes encoding xylanolytic enzymes in Aspergillus oryzae. Fungal Genet Biol, 35:157–169.
27.
NiermanW.C., PainA., AndersonM.J., WortmanJ.R., KimH.S., ArroyoJ.et al.2005. Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature, 438:1151–1156.
28.
OldhamM.C., HorvathS., GeschwindD.H.2006. Conservation and evolution of gene colexpression networks in human and chimpanzee brains. Proc Natl Acad Sci USA, 103:17973–17978.
29.
OliveiraA.P., PatilK.R., NielsenJ.2008. Architecture of transcriptional regulatory circuits is knitted over the topology of bio-molecular interaction networks. BMC Syst Biol, 2:17.
30.
PelH.J., de WindeJ.H., ArcherD.B., DyerP.S., HofmannG., SchaapP.J.et al.2007. Genome sequencing and analysis of the versatile cell factory Aspergillus niger CBS 513.88. Nat Biotechnol, 25:221–231.
31.
PayneG.A., NiermanW.C., WortmanJ.R., PritchardB.L., BrownD., DeanR.A.et al.2006. Whole genome comparison of Aspergillus flavus and A. oryzae. Med Mycol, 44:S9–S11.
32.
RamírezM.A., LorenzM.C.2009. The transcription factor homolog CTF1 regulates β-oxidation in Candida albicans. Eukaryotic Cell(in press).
33.
SalazarM., VongsangnakW., PanagiotouG., AndersenM.R., NielsenJ.2009. Uncovering transcriptional regulation of glycerol metabolism in Aspergilli through genome-wide gene expression data analysis. Mol Genet Genomics(in press).
SeoJ., HoffmanE.P.2006. Probe set algorithms: is there a rational best bet?BMC Bioinformatics, 7:395.
36.
ShenY.Q., BurgerG.2009. Plasticity of a key metabolic pathway in fungi. Funct Integr Genomics, 9:145–151.
37.
ShiL.M., PerkinsR.G., FangH., TongW.D.2008. Reproducible and reliable microarray results through quality control: good laboratory proficiency and appropriate data analysis practices are essential. Curr Opin Biotechnol, 19:10–18.
38.
SneathP., SokalR.R.1973. Numerical Taxonomy: The Principles and Practice of Numerical Classification. Freeman: San Francisco, CA, 573.
39.
TamayoE.N., VillanuevaA., HasperA.A., de GraaffL.H., RamonD., OrejasM.2008. CreA mediates repression of the regulatory gene xlnR which controls the production of xylanolytic enzymes in Aspergillus nidulans. Fungal Genet Biol, 45:984–1003.
TitorenkoV.I., RachubinskiR.A.2001. The life cycle of the peroxisome. Nat Rev Mol Cell Biol, 2:357–368.
43.
VandepoeleK., QuimbayaM., CasneufT., De VeylderL., Van de PeerY.2009. Unraveling transcriptional control in arabidopsis using cis-regulatory elements and coexpression networks. Plant Physiol, 150:535–546.
44.
van PeijN.N., VisserJ., de GraafJ.H.1998a. Isolation and analysis of xlnR, encoding a transcriptional activator co-ordinating xylanolytic expression in Aspergillus niger. Mol Microbiol, 27:131–142.
45.
van PeijN.N.M.E., GielkensM.M.C., de VriesR.P., VisserJ., de GraaffL.H.1998b. The transcriptional activator XlnR regulates both xylanolytic and endoglucanase gene expression in Aspergillus niger. Appl Environ Microbiol, 64:3615–3619.
46.
VongsangnakW., OlsenP., HansenH., KrogsgaardS., NielsenJ.2008. Improved annotation through genome-scale metabolic modeling of Aspergillus oryzae. BMC Genomics, 9.
47.
VongsangnakW., SalazarM., HansenH., NielsenJ.2009. Genome-wide analysis of maltose utilization and regulation in aspergilli. Microbiology, 155:3893–3902.
48.
WolfsbergT.G., GabrielianA.E., CampbellM.J., ChoR.J., SpougeJ.L., LandsmanD.1999. Candidate regulatory sequence elements for cell cycle-dependent transcription in Saccharomyces cerevisiae. Genome Res, 9:775–792.
49.
WorkmanC., JensenL.J., JarmerH., BerkaR., GautierL., NielsenH.B.et al.2002. A new non-linear normalization method for reducing variability in DNA microarray experiments. Genome Biol, 3.
50.
YoungE.T., DombekK.M., TachibanaC., IdekerT.2003. Multiple pathways are co-regulated by the protein kinase Snf1 and the transcription factors Adr1 and Cat8. J Biol Chem, 278:26146–26158.
51.
ZuckerkandlE., PaulingL.1965. Evolutionary divergence and convergence in proteins. Evolving Genes and Proteins. BrysonV., H.J.Vogel Academic Press: New York, 97–166.
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