Genome-wide expression analysis upon constitutive activation of the HacA bZIP transcription factor in Aspergillus niger reveals a coordinated cellular response to counteract ER stress

被引:39
作者
Carvalho, Neuza D. S. P. [1 ,2 ]
Jorgensen, Thomas R. [1 ,2 ]
Arentshorst, Mark [1 ]
Nitsche, Benjamin M. [1 ]
van den Hondel, Cees A. M. J. J. [1 ,2 ]
Archer, David B. [3 ]
Ram, Arthur F. J. [1 ,2 ]
机构
[1] Leiden Univ, Inst Biol Leiden, NL-2333 BE Leiden, Netherlands
[2] Kluyver Ctr Genom Ind Fermentat, NL-2600 GA Delft, Netherlands
[3] Univ Nottingham, Sch Biol, Nottingham NG7 2RD, England
来源
BMC GENOMICS | 2012年 / 13卷
基金
英国生物技术与生命科学研究理事会;
关键词
HacA; Unfolded protein response; Secretion stress; RESS; XBP1; Aspergillus niger; Protein secretion; UNFOLDED-PROTEIN RESPONSE; ENDOPLASMIC-RETICULUM STRESS; MESSENGER-RNA; TRICHODERMA-REESEI; FILAMENTOUS FUNGI; SECRETION STRESS; SACCHAROMYCES-CEREVISIAE; DOWN-REGULATION; GENES; PATHWAY;
D O I
10.1186/1471-2164-13-350
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: HacA/Xbp1 is a conserved bZIP transcription factor in eukaryotic cells which regulates gene expression in response to various forms of secretion stress and as part of secretory cell differentiation. In the present study, we replaced the endogenous hacA gene of an Aspergillus niger strain with a gene encoding a constitutively active form of the HacA transcription factor (HacA(CA)). The impact of constitutive HacA activity during exponential growth was explored in bioreactor controlled cultures using transcriptomic analysis to identify affected genes and processes. Results: Transcription profiles for the wild-type strain (HacA(WT)) and the HacACA strain were obtained using Affymetrix GeneChip analysis of three replicate batch cultures of each strain. In addition to the well known HacA targets such as the ER resident foldases and chaperones, GO enrichment analysis revealed up-regulation of genes involved in protein glycosylation, phospholipid biosynthesis, intracellular protein transport, exocytosis and protein complex assembly in the HacACA mutant. Biological processes over-represented in the down-regulated genes include those belonging to central metabolic pathways, translation and transcription. A remarkable transcriptional response in the HacACA strain was the down-regulation of the AmyR transcription factor and its target genes. Conclusions: The results indicate that the constitutive activation of the HacA leads to a coordinated regulation of the folding and secretion capacity of the cell, but with consequences on growth and fungal physiology to reduce secretion stress.
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页数:17
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