Ace2 transcription factor family genes are found in many fungal genomes and are required for regulation of expression of genes involved in cell separation. We used transcriptional profiling to identify the targets of Ace2 in Candida albicans, and we show that these include several cell wall components, such as glucanases and glycosylphosphatidylinositol-anchored proteins. Expression is downregulated in ace2 deletion mutants in both yeast and hyphal cells. In addition, deleting ace2 results in dramatic changes in expression of metabolic pathways. Expression of glycolytic enzymes is reduced, while expression of respiratory genes (including those involved in the tricarboxylic acid cycle, oxidative phosphorylation, and ATP synthesis) is increased. Similar changes occur in both yeast and hyphal cells. In contrast, genes required for acetyl-coenzyme A and lipid metabolism are upregulated in an ace2 deletion mutant grown predominantly as yeast cells but are downregulated in hyphae. These results suggest that in wild-type strains, Ace2 acts to increase glycolysis and reduce respiration. This is supported by the observation that deleting ace2 results in increased resistance to antimycin A, a drug that inhibits respiration. We also show that Ace2 is required for filamentation in response to low oxygen concentrations (hypoxia). We suggest that filamentation is induced in wild-type cells by reducing respiration (using low oxygen or respiratory drugs) and that mutants with increased respiratory activity fail to undergo filamentation under these conditions.In Saccharomyces cerevisiae, ACE2 and SWI5 encode two of a set of nine transcription factors that control the mitotic cell cycle (40). The nine regulators are SBF (Swi4 and Swi6) and MBF (Swi6 and Mbp1), which control the expression of genes in G 1 and S phase (18); Ndd1, Fkh1, Fkh2, and Mcm1, which regulate the expression of genes at the G 2 /M border; and Swi5 and Ace2 (and Mcm1), which control the expression of genes in late M and early G 1 . The transcription factors act in a cascade: SBF and MBF regulate expression of NDD1, the G 2 activators control expression of ACE2 and SWI5, and these in turn are required for exit from mitosis and subsequent activation of SBF and MBF.Ace2 and Swi5 share many functional similarities in S. cerevisiae. The proteins are 37% identical and have the same DNA-binding sites in vitro (29). They also regulate the expression of many of the same genes (9). However, there are substantial differences. There is only ϳ22% overlap between the groups of genes regulated by the two factors (40). Swi5 remains cytoplasmic until the end of M phase, when it enters the nucleus (33). Ace2 also enters the nucleus at the end of mitosis (35) but is rapidly exported from (or degraded in) the nucleus of the mother cell and remains only in the nucleus of the daughter cell (7, 46). Localization is regulated by components of the RAM pathway (34, 38). Expression of many Ace2 targets is therefore restricted to the daughter cell, and one of their main functions is to e...