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Vol. 19, Issue 10, 4260-4272, October 2008

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Efg1-mediated Recruitment of NuA4 to Promoters Is Required for Hypha-specific Swi/Snf Binding and Activation in Candida albicans

Yang Lu^*, Chang Su^*, Xuming Mao^*, Prashna Pala Raniga, Haoping Liu, and Jiangye Chen^*

*State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, SIBS, Chinese Academy of Sciences, Shanghai 200031, China; and Department of Biological Chemistry, College of Medicine, University of California, Irvine, Irvine, CA 92697-1700

Submitted February 19, 2008; Revised July 24, 2008; Accepted July 29, 2008
Monitoring Editor: Thomas D. Fox

Efg1 is essential for hyphal development and virulence in the human pathogenic fungus Candida albicans. How Efg1 regulates gene expression is unknown. Here, we show that Efg1 interacts with components of the nucleosome acetyltransferase of H4 (NuA4) histone acetyltransferase (HAT) complex in both yeast and hyphal cells. Deleting YNG2, a subunit of the NuA4 HAT module, results in a significant decrease in the acetylation level of nucleosomal H4 and a profound defect in hyphal development, as well as a defect in the expression of hypha-specific genes. Using chromatin immunoprecipitation, Efg1 and the NuA4 complex are found at the UAS regions of hypha-specific genes in both yeast and hyphal cells, and Efg1 is required for the recruitment of NuA4. Nucleosomal H4 acetylation at the promoters peaks during initial hyphal induction in an Efg1-dependent manner. We also find that Efg1 bound to the promoters of hypha-specific genes is critical for recruitment of the Swi/Snf chromatin remodeling complex during hyphal induction. Our data show that the recruitment of the NuA4 complex by Efg1 to the promoters of hypha-specific genes is required for nucleosomal H4 acetylation at the promoters during hyphal induction and for subsequent binding of Swi/Snf and transcriptional activation.

Address correspondence to: Haoping Liu (h4liu{at}uci.edu) or Jiangye Chen (jychen{at}sunm.shcnc.ac.cn)

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