Reference: Hickman MJ and Winston F (2007) Heme Levels Switch the Function of Hap1 of Saccharomyces cerevisiae between Transcriptional Activator and Transcriptional Repressor. Mol Cell Biol 27(21):7414-24

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Abstract


Changes in oxygen levels cause widespread changes in gene expression in organisms ranging from bacteria to humans. In Saccharomyces cerevisiae, this response is mediated in part by Hap1, originally identified as a heme-dependent transcriptional activator that functions during aerobic growth. We show here that Hap1 also plays a significant and direct role under hypoxic conditions, not as an activator but as a repressor. The repressive activity of Hap1 controls several genes, including three ERG genes required for ergosterol biosynthesis. Chromatin immunoprecipitation experiments show that Hap1 binds to the ERG gene promoters, while additional experiments show that the corepressor Tup1/Ssn6 is recruited by Hap1 and is also required for repression. Furthermore, mutational analysis demonstrates that conserved Hap1 binding sites in the ERG5 5' regulatory region are required for repression. The switch of Hap1 between acting as a hypoxic repressor and an aerobic activator is determined by heme, which is synthesized only in the presence of oxygen. The ability of Hap1 to function as a ligand-dependent repressor and activator is a property shared with mammalian nuclear hormone receptors, and likely allows greater transcriptional control by Hap1 in response to changing oxygen levels.

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Journal Article
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Hickman MJ, Winston F
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