Su Chang, Li Yandong, Lu Yang, Chen Jiangye
State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, SIBS, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Eukaryot Cell. 2009 Nov;8(11):1780-91. doi: 10.1128/EC.00190-09. Epub 2009 Sep 4.
Candida albicans undergoes a morphological transition from yeast to hyphae in response to a variety of stimuli and growth conditions. We previously isolated a LisH domain containing transcription factor Flo8, which is essential for hyphal development in C. albicans. To search the putative binding partner of Flo8 in C. albicans, we identified C. albicans Mss11, a functional homolog of Saccharomyces cerevisiae Mss11, which also contains a LisH motif at its N terminus. C. albicans Mss11 can interact with Flo8 via the LisH motif by in vivo coimmunoprecipitation. The results of a chromatin immunoprecipitation (ChIP) assay showed that more Mss11 and Flo8 proteins bound to the upstream activating sequence region of HWP1 promoter in hyphal cells than in yeast cells, and the increased binding of each of these two proteins responding to hyphal induction was dependent on the other. Overexpression of MSS11 enhanced filamentous growth. Deletion of MSS11 caused a profound defect in hyphal development and the induction of hypha-specific genes. Our data suggest that Mss11 functions as an activator in hyphal development of C. albicans. Furthermore, overexpression of FLO8 can bypass the requirement of Mss11 in filamentous formation, whereas overexpression of MSS11 failed to promote hyphae growth in flo8 mutants. In summary, we show that the expression level of MSS11 increases during hyphal induction, and the enhanced expression of MSS11 may contribute to cooperative binding of Mss11 and Flo8 to the HWP1 promoter.
白色念珠菌会根据多种刺激和生长条件经历从酵母形态到菌丝形态的转变。我们之前分离出了一种含有LisH结构域的转录因子Flo8，它对于白色念珠菌的菌丝发育至关重要。为了寻找白色念珠菌中Flo8的假定结合伴侣，我们鉴定出了白色念珠菌Mss11，它是酿酒酵母Mss11的功能同源物，其N端也含有一个LisH基序。通过体内共免疫沉淀实验，白色念珠菌Mss11可通过LisH基序与Flo8相互作用。染色质免疫沉淀（ChIP）分析结果表明，与酵母细胞相比，菌丝细胞中有更多的Mss11和Flo8蛋白结合到HWP1启动子的上游激活序列区域，并且这两种蛋白中每种蛋白对菌丝诱导的结合增加都依赖于另一种蛋白。MSS11的过表达增强了丝状生长。MSS11的缺失导致菌丝发育以及菌丝特异性基因诱导方面出现严重缺陷。我们的数据表明，Mss11在白色念珠菌的菌丝发育中起激活剂的作用。此外，FLO8的过表达可以绕过丝状形成中对Mss11的需求，而MSS11的过表达未能促进flo8突变体中的菌丝生长。总之，我们表明在菌丝诱导过程中MSS11的表达水平增加，并且MSS11表达的增强可能有助于Mss11和Flo8协同结合到HWP1启动子上。
