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.
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.
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DOI：
10.1186/1471-2164-13-350
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发表时间：
2012-07-30
期刊：
影响因子：
4.4
通讯作者：
Ram AF
中科院分区：
文献类型：
--
作者：
Carvalho ND;Jørgensen TR;Arentshorst M;Nitsche BM;van den Hondel CA;Archer DB;Ram AF
HacA/Xbp 1是真核细胞中保守的bZIP转录因子，它调节基因表达以响应各种形式的分泌应激并作为分泌细胞分化的一部分。在本研究中，我们用编码组成型活性形式的HacA转录因子（HacACA）的基因替换了尼日尔曲霉菌株的内源性hacA基因。在生物反应器控制的培养物中，使用转录组学分析探索指数生长期间组成型HacA活性的影响，以鉴定受影响的基因和过程。野生型菌株（HacAWT）和HacACA菌株的转录谱是使用Affyssin GeneChip分析每种菌株的三个重复批次培养物获得的。除了众所周知的HacA靶标如ER驻留折叠酶和分子伴侣外，GO富集分析揭示了HacACA突变体中参与蛋白糖基化、磷脂生物合成、细胞内蛋白转运、胞吐和蛋白复合物组装的基因的上调。在下调基因中过度表达的生物学过程包括那些属于中心代谢途径、翻译和转录的过程。一个显着的转录反应在HacACA株的AmyR转录因子及其靶基因的下调。结果表明，HacA的组成性激活导致细胞的折叠和分泌能力的协调调节，但对生长和真菌生理学的后果，以减少分泌应激。
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. 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. 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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影响因子：
12.3
作者：
Gentleman RC;Carey VJ;Bates DM;Bolstad B;Dettling M;Dudoit S;Ellis B;Gautier L;Ge Y;Gentry J;Hornik K;Hothorn T;Huber W;Iacus S;Irizarry R;Leisch F;Li C;Maechler M;Rossini AJ;Sawitzki G;Smith C;Smyth G;Tierney L;Yang JY;Zhang J
通讯作者：
Zhang J
影响因子：
16
作者：
Harding, HP;Zhang, YH;Ron, D
通讯作者：
Ron, D
影响因子：
16
作者：
Harding, HP;Novoa, I;Ron, D
通讯作者：
Ron, D
影响因子：
2.5
作者：
DERUITERJACOBS, YMJT;BROEKHUIJSEN, M;VANDENHONDEL, CAMJJ
通讯作者：
VANDENHONDEL, CAMJJ
影响因子：
3.6
作者：
Al-Sheikh, H;Watson, AJ;Archer, DB
通讯作者：
Archer, DB