Fig. 7. Positive and negative regulation of gene expression in yeast. Under anaerobic conditions the LORE-BP (low oxygen response element binding protein) is activated. The mechanism of activation parallels that of higher eukaryotes insofar as anaerobic induction can be mimicked by transition metals and desferroximine. The possible involvement of a proline-hydroxyproline active site has not been demonstrated in this system as it has in the HIF-1 pathway (see Fig. 9). LORE-BP is a positive-acting transcription factor that binds and activates hypoxia-response genes with the sequence ACTCAACAA. The HAP1-Rox-1 pathway operates in parallel with the LORE pathway. HAP-1 requires heme as a cofactor and is activated under aerobic conditions when heme levels are high. HAP-1 is a positive transcription factor for multiple aerobic genes (genes required for aerobic metabolism and functions) through binding to the recognition sequence CGG(N6)CGG. The ROX-1 promoter region contains the HAP-1 binding site and is activated by HAP-1. ROX-1 is a repressor that negatively regulates (hypoxic) genes containing the sequence CCATTGTTCTC. Consequently HAP-1 coordinately regulates both aerobic and hypoxic genes.

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