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Open Access Research article

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

Neuza DSP Carvalho12, Thomas R Jørgensen124, Mark Arentshorst1, Benjamin M Nitsche15, Cees AMJJ van den Hondel12, David B Archer3 and Arthur FJ Ram12*

Author Affiliations

1 Institute of Biology Leiden, Leiden University, Molecular Microbiology and Biotechnology, Sylviusweg 72, 2333, BE Leiden, The Netherlands

2 Kluyver Centre for Genomics of Industrial Fermentation, P.O box 5057, 2600, GA Delft, The Netherlands

3 School of Biology, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom

4 Present address: Protein Expression, Novo Nordisk, Novo Nordisk Park, 2760, Måløv, Denmark

5 Present address: Applied and Molecular Microbiology, Institute of Biotechnology, Berlin University of Technology, Gustav-Meyer-Allee 25, 13355, Berlin, Germany

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BMC Genomics 2012, 13:350  doi:10.1186/1471-2164-13-350

Published: 30 July 2012

Abstract

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 (HacACA). 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 (HacAWT) 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.

Keywords:
HacA; Unfolded protein response; Secretion stress; RESS; XBP1; Aspergillus niger; Protein secretion