Figure 9.

Regulatory roles of Cir1 and HapX in response to iron availability. The possible regulatory roles of Cir1 and HapX are indicated under iron-limited and iron-replete conditions. During iron deprivation, HapX forms a heteromeric complex with Hap2, Hap3, and Hap5, and represses genes involved in iron utilization (e.g., for ISC biosynthesis, heme biosynthesis, mitochondrial respiration, and iron-containing proteins). Under the same conditions, Cir1, together with Grx4, positively governs the expression of genes required for iron uptake, including reductive iron uptake, siderophore uptake, and heme uptake systems. Under iron-replete conditions, HapX incorporates iron and positively regulates reductive iron uptake genes, while iron-containing Cir1 represses the genes encoding iron uptake systems. The regulatory interactions between HapX and Cir1 are also indicated and include direct and negative control of HAPX transcription by Cir1 under the high iron condition. Direct interactions were not observed under low iron conditions, although modest and indirect regulation of Cir1 by HapX may occur (indicated by a dashed line), as suggested by previous microarray analyses (Jung et al. 2010)