Regulation of the CYB2 gene expression: transcriptional co-ordination by the Hap1p, Hap2/3/4/5p and Adr1p transcription factors

Expression of the Saccharomyces cerevisiae nuclear gene CYB2 encoding the m itochondrial enzyme L-(+)-lactate-cytochrome c oxidoreductase (EC 1.2.2.3) is subject to several strict metabolic controls at the transcriptional leve l: repression due to glucose fermentation, derepression by ethanol, inducti on by lactate and inhibition under anaerobic conditions or in response to d eficiency of haem biosynthesis, In this respect, the data obtained from the transcriptional analysis of the CYB2 gene contribute to a better understan ding of the control of mitochondrial biogenesis, in this study, we show tha t Hap1p is the main transcriptional activator involved in the control of CY B2 transcription. We found that Hap1p activity, known to be oxygen dependen t, is effected by DNA-protein interaction with two binding sites present in the CYB2 promoter. Control is moreover dependent on carbon sources. This r egulation by the carbon substrates is subordinate to the activity of the co mplex Hap2/3/4/5p, which counteracts the negative effect of the URS1 elemen t. Finally, our results suggest that the Adr1p transcriptional activator is also required in CYB2 transcription control. This work provides new data w hich allows a better understanding of the molecular mechanisms implicated i n the co-regulation at the transcriptional level of the genes encoding prot eins involved in various aspects of oxidative metabolism.