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Mot3 is a transcriptional repressor of ergosterol biosynthetic genes and is required for normal vacuolar function in Saccharomyces cerevisiae
Author(s) -
Hongay Cintia,
Jia Nan,
Bard Martin,
Winston Fred
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf415
Subject(s) - biology , saccharomyces cerevisiae , ergosterol , repressor , gene , function (biology) , genetics , saccharomyces , fungal protein , microbiology and biotechnology , biochemistry , gene expression
The Saccharomyces cerevisiae MOT3 gene encodes a nuclear protein implicated in both repression and activation of transcription. However, a mot3Δ mutation causes only mild phenotypes under normal growth conditions. To learn more about Mot3 function, we have performed a synthetic lethal screen. This screen identified PAN1 , a gene required for normal endocytosis, and VPS41 , a gene required for vacuolar fusion and protein targeting, suggesting a role for Mot3 in the regulation of membrane‐related genes. Transcriptional analyses show that Mot3 represses transcription of ERG2, ERG6 and ERG9 , genes required for ergosterol biosynthesis, during both aerobic and hypoxic growth. Chromatin immunoprecipitation experiments suggest that this repression is direct. Ergosterol has been shown to be required for endocytosis and homotypic vacuole fusion, providing a link between Mot3 and these processes. Consistent with these results, mot3Δ mutants have a number of related defects, including impaired homotypic vacuole fusion and increased sterol levels. Taken together, our data suggest that proper transcriptional regulation of ergosterol biosynthetic genes by Mot3 is important for normal vacuolar function and probably for the endocytic membrane transport system.