The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess.
The Janus transcription factor HapX controls fungal adaptation to both iron starvation and iron excess.
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DOI：
10.15252/embj.201489468
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发表时间：
2014-10-01
期刊：
影响因子：
--
通讯作者：
Haas H
中科院分区：
文献类型：
--
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
铁的生理水平的平衡对每个生物体都是必不可少的。在烟曲霉和其他真菌病原体中，转录因子HapX通过抑制铁消耗和激活铁吸收来介导对铁限制的适应，从而介导毒力。在这里，我们证明了HapX也是通过激活液泡铁储存的铁抗性所必需的。我们确定了在铁饥饿或高铁条件下对HapX功能至关重要的HapX蛋白结构域。这些结构域的进化保守性表明它们在铁传感中的广泛作用。我们进一步证明了HapX同源二聚体和CCAAT结合复合物（CBC）合作结合靶启动子中进化保守的DNA基序。后者揭示了一般CBC和特异性HapX/CBC靶基因之间的区分模式。总的来说，我们的研究揭示了一种新的调节机制，通过相同的转录因子复合物介导铁抗性和适应铁饥饿，其激活和抑制功能取决于环境铁的可用性。
Balance of physiological levels of iron is essential for every organism. In Aspergillus fumigatus and other fungal pathogens, the transcription factor HapX mediates adaptation to iron limitation and consequently virulence by repressing iron consumption and activating iron uptake. Here, we demonstrate that HapX is also essential for iron resistance via activating vacuolar iron storage. We identified HapX protein domains that are essential for HapX functions during either iron starvation or high-iron conditions. The evolutionary conservation of these domains indicates their wide-spread role in iron sensing. We further demonstrate that a HapX homodimer and the CCAAT-binding complex (CBC) cooperatively bind an evolutionary conserved DNA motif in a target promoter. The latter reveals the mode of discrimination between general CBC and specific HapX/CBC target genes. Collectively, our study uncovers a novel regulatory mechanism mediating both iron resistance and adaptation to iron starvation by the same transcription factor complex with activating and repressing functions depending on ambient iron availability.
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