Target specificity of the Candida albicans Efg1 regulator
Target specificity of the Candida albicans Efg1 regulator
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DOI：
10.1111/j.1365-2958.2011.07837.x
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发表时间：
2011-11-01
影响因子：
3.6
通讯作者：
Ernst, Joachim F.
中科院分区：
文献类型：
--
作者：
Lassak, Theresia;Schneider, Eva;Ernst, Joachim F.
Efg 1是白色念珠菌形态发生和代谢的核心转录调节因子。体内全基因组ChIP芯片和体外足迹分析揭示了Efg 1识别序列（EGFR盒）TATGCATA在酵母生长形式的这种人类真菌病原体。EFG 1和编码菌丝生长转录调节因子的基因（包括TCC 1、CZF 1、TEC 1、DEF 1和NRG 1）的上游区域含有EGR和/或EGR样盒。出乎意料的是，经过短暂的菌丝诱导后，全基因组Efg 1结合模式完全改变，出现了特异性未知的新结合位点。菌丝诱导废除EFG 1和TCC 1启动子上的EFG 1积累，并导致这两个成绩单的快速下降，虽然EFG 1蛋白在细胞中持续存在。虽然EFG 1启动子活性在酵母生长形式不依赖于结合EFG 1，其下调菌丝诱导下依赖于EFG 1和蛋白激酶A亚型Tpk 2的存在。对EFG 1上游区域的缺失分析表明，没有一个常驻EGR盒是EFG 1启动子下调的唯一原因。这些结果表明Efg 1在酵母生长和菌丝诱导中具有不同的结合特异性，并表明菌丝诱导后的一个短暂的时间窗口，其中Efg 1对靶启动子发挥其抑制作用。
Efg1 is a central transcriptional regulator of morphogenesis and metabolism in Candida albicans. In vivo genome-wide ChIP chip and in vitro footprint analyses revealed the Efg1 recognition sequence (EGR-box) TATGCATA in the yeast growth form of this human fungal pathogen. Upstream regions of EFG1 and genes encoding transcriptional regulators of hyphal growth including TCC1, CZF1, TEC1, DEF1 and NRG1 contained EGR- and/or EGR- like boxes. Unexpectedly, after brief hyphal induction the genome-wide Efg1 binding pattern was completely altered and new binding sites of yet unknown specificity had appeared. Hyphal induction abolished Efg1 accumulation on EFG1 and TCC1 promoters and led to rapid decline of both transcripts, although the Efg1 protein persisted in cells. While EFG1 promoter activity in the yeast growth form did not depend on bound Efg1, its downregulation under hyphal induction depended on the presence of Efg1 and the protein kinase A isoform Tpk2. Deletion analyses of the EFG1 upstream region revealed that none of its resident EGR- boxes is uniquely responsible for EFG1 promoter downregulation. These results suggest different binding specificities of Efg1 in yeast growth and in hyphal induction and suggest a brief time window following hyphal induction, in which Efg1 exerts its repressive effect on target promoters.