Regulation of High-Affinity Iron Acquisition, Including Acquisition Mediated by the Iron Permease FtrA, Is Coordinated by AtrR, SrbA, and SreA in Aspergillus fumigatus.
Regulation of High-Affinity Iron Acquisition, Including Acquisition Mediated by the Iron Permease FtrA, Is Coordinated by AtrR, SrbA, and SreA in Aspergillus fumigatus.
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作者：
铁的获得对人类病原体烟曲霉的毒力至关重要。以前的研究表明，这种霉菌通过铁载体和还原性铁同化的加塔因子SreA和SREBP调节剂SrbA来调节铁的吸收。在这里，功能丧失以及过度活跃的等位基因的表征表明，铁吸收的转录激活还取决于Zn 2Cys 6调节剂AtrR，最有可能通过与SrbA的合作。铁渗透酶编码ftrA基因的启动子的突变分析确定了一个210 bp的序列，这是必不可少的，足以赋予铁调节。进一步的研究定位的功能序列，密集包装在75 bp内，在很大程度上类似于SrbA，SreA和AtrR的结合基序。后者经染色质免疫沉淀（ChIP）分析证实，是第一个与5′-CGGN 12 CCG-3′共有序列不完全匹配的序列。这里提出的结果首次强调SrbA，AtrR和SreA在铁调节的直接参与。AtrR和SrbA在激活铁获得中的重要作用强调了铁稳态与麦角固醇和血红素的生物合成以及对缺氧的适应的协调。其基本原理很可能是这些途径的铁依赖性沿着麦角固醇和铁载体生物合成的酶促联系。
Iron acquisition is crucial for virulence of the human pathogen Aspergillus fumigatus. Previous studies indicated that this mold regulates iron uptake via both siderophores and reductive iron assimilation by the GATA factor SreA and the SREBP regulator SrbA. Here, characterization of loss of function as well as hyperactive alleles revealed that transcriptional activation of iron uptake depends additionally on the Zn2Cys6 regulator AtrR, most likely via cooperation with SrbA. Mutational analysis of the promoter of the iron permease-encoding ftrA gene identified a 210-bp sequence, which is both essential and sufficient to impart iron regulation. Further studies located functional sequences, densely packed within 75 bp, that largely resemble binding motifs for SrbA, SreA, and AtrR. The latter, confirmed by chromatin immunoprecipitation (ChIP) analysis, is the first one not fully matching the 5′-CGGN12CCG-3′ consensus sequence. The results presented here emphasize for the first time the direct involvement of SrbA, AtrR, and SreA in iron regulation. The essential role of both AtrR and SrbA in activation of iron acquisition underlines the coordination of iron homeostasis with biosynthesis of ergosterol and heme as well as adaptation to hypoxia. The rationale is most likely the iron dependence of these pathways along with the enzymatic link of biosynthesis of ergosterol and siderophores.
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影响因子：
2.9
作者：
Bertuzzi M;van Rhijn N;Krappmann S;Bowyer P;Bromley MJ;Bignell EM
通讯作者：
Bignell EM
影响因子：
5.7
作者：
Huber, Eva M.;Hortschansky, Peter;Groll, Michael
通讯作者：
Groll, Michael
DOI：
10.15252/embj.201489468
发表时间：
2014-10-01
期刊：
The EMBO journal
影响因子：
--
作者：
Gsaller F;Hortschansky P;Beattie SR;Klammer V;Tuppatsch K;Lechner BE;Rietzschel N;Werner ER;Vogan AA;Chung D;Mühlenhoff U;Kato M;Cramer RA;Brakhage AA;Haas H
通讯作者：
Haas H
影响因子：
6.7
作者：
Hagiwara D;Miura D;Shimizu K;Paul S;Ohba A;Gonoi T;Watanabe A;Kamei K;Shintani T;Moye-Rowley WS;Kawamoto S;Gomi K
通讯作者：
Gomi K
影响因子：
4.8
作者：
Paul S;Bowyer P;Bromley M;Moye-Rowley WS
通讯作者：
Moye-Rowley WS