The zinc cluster transcription factor Ahr1p directs Mcm1p regulation of Candida albicans adhesion
The zinc cluster transcription factor Ahr1p directs Mcm1p regulation of Candida albicans adhesion
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DOI：
10.1111/j.1365-2958.2010.07504.x
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发表时间：
2011-02-01
影响因子：
3.6
通讯作者：
Whiteway, Malcolm
中科院分区：
文献类型：
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作者：
Askew, Christopher;Sellam, Adnane;Whiteway, Malcolm
白色念珠菌的生物膜发展需要细胞粘附以初步建立生物膜，并在菌丝发展后保持持续稳定;然而，该过程的调控尚未完全建立。使用染色质免疫沉淀耦合到微阵列分析（ChIP芯片），我们已经确定了一个调节子包含的Mcm 1 p因子，所需的初始表面粘附在生物膜形成过程中。在酵母酿酒酵母中，几种Mcm 1 p调节子的特征在于通过辅因子结合邻近Mcm 1 p结合位点的序列来实现调节特异性。这种新的Mcm 1 p调节子在C.白色念珠菌还需要一个辅因子，我们确定为转录因子Ahr 1 p。然而，与其他酵母调节子相反，Ahr 1 p单独结合靶启动子，其中包括几个关键的粘附基因，并将Mcm 1 p招募到这些位点。通过转录谱分析和qPCR分析，我们证明了这种Ahr 1 p-Mcm 1 p复合物直接激活这些粘附基因。当通过删除AHR 1破坏调节回路时，菌株显示出对聚苯乙烯表面的粘附性降低。我们还证明了调节子在菌丝生长和毒力中的作用。因此，我们的工作建立了一个新的机制，Mcm 1 p指导的监管不同于其他Mcm 1 p的共同监管机构所观察到的。
Biofilm development by Candida albicans requires cell adhesion for the initial establishment of the biofilm and the continued stability after hyphal development occurs; however, the regulation of the process has not been fully established. Using chromatin immunoprecipitation coupled to microarray analysis (ChIP-chip) we have characterized a regulon containing the Mcm1p factor that is required for the initial surface adhesion during biofilm formation. In the yeast Saccharomyces cerevisiae several Mcm1p regulons have been characterized in which regulatory specificity is achieved through cofactors binding a sequence adjacent to the Mcm1p binding site. This new Mcm1p regulon in C. albicans also requires a cofactor, which we identify as the transcription factor Ahr1p. However, in contrast to the other yeast regulons, Ahr1p alone binds the target promoters, which include several key adhesion genes, and recruits Mcm1p to these sites. Through transcription profiling and qPCR analysis, we demonstrate that this Ahr1p-Mcm1p complex directly activates these adhesion genes. When the regulatory circuit was disrupted by deleting AHR1, the strain displayed reduced adherence to a polystyrene surface. We also demonstrate a role for the regulon in hyphal growth and in virulence. Our work thus establishes a new mechanism of Mcm1p-directed regulation distinct from those observed for other Mcm1p co-regulators.