Department of Biochemistry and Biophysics, University of California, San Francisco, California 94158, USA.
Genetics. 2012 Feb;190(2):511-21. doi: 10.1534/genetics.111.134080. Epub 2011 Nov 17.
Fungi exhibit a large variety of morphological forms. Here, we examine the functions of a deeply conserved regulator of morphology in three fungal species: Saccharomyces cerevisiae, Candida albicans, and Histoplasma capsulatum. We show that, despite an estimated 600 million years since those species diverged from a common ancestor, Wor1 in C. albicans, Ryp1 in H. capsulatum, and Mit1 in S. cerevisiae are transcriptional regulators that recognize the same DNA sequence. Previous work established that Wor1 regulates white-opaque switching in C. albicans and that its ortholog Ryp1 regulates the yeast to mycelial transition in H. capsulatum. Here we show that the ortholog Mit1 in S. cerevisiae is also a master regulator of a morphological transition, in this case pseudohyphal growth. Full-genome chromatin immunoprecipitation experiments show that Mit1 binds to the control regions of the previously known regulators of pseudohyphal growth as well as those of many additional genes. Through a comparison of binding sites for Mit1 in S. cerevisiae, Wor1 in C. albicans, and Wor1 ectopically expressed in S. cerevisiae, we conclude that the genes controlled by the orthologous regulators overlap only slightly between these two species despite the fact that the DNA binding specificity of the regulators has remained largely unchanged. We suggest that the ancestral Wor1/Mit1/Ryp1 protein controlled aspects of cell morphology and that movement of genes in and out of the Wor1/Mit1/Ryp1 regulon is responsible, in part, for the differences of morphological forms among these species.
真菌表现出多种形态。在这里，我们研究了形态学的一个深保守调节剂在三个真菌物种中的功能：酿酒酵母、白色念珠菌和荚膜组织胞浆菌。我们表明，尽管这些物种与共同祖先分化了大约 6 亿年，但白色念珠菌中的 Wor1、荚膜组织胞浆菌中的 Ryp1 和酿酒酵母中的 Mit1 是识别相同 DNA 序列的转录调节剂。先前的工作表明，Wor1 调节白色念珠菌中的白-暗转换，其同源物 Ryp1 调节荚膜组织胞浆菌中的酵母向菌丝体的转变。在这里，我们表明酿酒酵母中的同源物 Mit1 也是一种形态转变的主要调节剂，在这种情况下是假菌丝生长。全基因组染色质免疫沉淀实验表明，Mit1 结合了假菌丝生长的先前已知调节剂的控制区，以及许多其他基因的控制区。通过比较酿酒酵母中的 Mit1、白色念珠菌中的 Wor1 和酿酒酵母中异位表达的 Wor1 的结合位点，我们得出结论，尽管调节剂的 DNA 结合特异性在很大程度上保持不变，但两个物种中受同源调节剂控制的基因仅略有重叠。我们认为，祖先 Wor1/Mit1/Ryp1 蛋白控制细胞形态的各个方面，并且基因在 Wor1/Mit1/Ryp1 调控子内外的移动部分导致了这些物种之间形态形式的差异。
