title: Transcriptional regulation by Lge1p requires a function independent of its role in histone H2B ubiquitination.
abstract: Saccharomyces cerevisiae cells that have lost their mitochondrial genome (rho(0)) strongly induce transcription of multidrug resistance genes, including the ATP-binding cassette transporter gene PDR5. PDR5 induction in rho(0) cells requires the presence of the zinc cluster transcription factor Pdr3p. The PDR3 gene is positively autoregulated in rho(0) cells by virtue of the presence of two binding sites for Pdr3p in its promoter. We identify the novel protein Lge1p as a required participant in the rho(0) activation of PDR3 and PDR5 expression. Lge1p is a nuclear protein that has been found to play a role in ubiquitination of histone H2B at Lys(123). This ubiquitination requires the presence of the ubiquitin-conjugating enzyme Rad6p and the ubiquitin ligase Bre1p. Interestingly, rho(0) strains lacking Lge1p failed to induce PDR3 transcription, but induction was still seen in Deltarad6, Deltabre1, and H2B-K123R mutant strains. Microarray experiments also confirmed that the pattern of gene expression changes seen in cells lacking Lge1p, Bre1p, or Rad6p or containing the H2B-K123R mutant as the only form of H2B share some overlap but are distinct. These findings provide a strong argument that Lge1p has roles in gene regulation independent of its participation in the Rad6p-dependent ubiquitination of H2B.
authors.affiliation: Department of Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, USA.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Zhang
authors.forename: Ania
authors.initials: A
authors.lastname: Kolaczkowska
authors.forename: Frédéric
authors.initials: F
authors.lastname: Devaux
authors.forename: Sneh Lata
authors.initials: SL
authors.lastname: Panwar
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Hallstrom
authors.forename: Claude
authors.initials: C
authors.lastname: Jacq
authors.forename: W Scott
authors.initials: WS
authors.lastname: Moye-Rowley
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D015152:Blotting, Northern; D002467:Cell Nucleus / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D018432:Drug Resistance, Multiple; D015966:Gene Expression Regulation, Fungal; D005838:Genotype; D006657:Histones / Q000378:metabolism*; D007763:Lac Operon; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010957:Plasmids / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D015032:Zinc / Q000378:metabolism; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D006657:Histones; C497163:Lge1 protein, S cerevisiae; C089261:PDR3 protein, S cerevisiae; C092438:PDR5 protein, S cerevisiae; D011500:Protein Synthesis Inhibitors; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D025801:Ubiquitin; D004247:DNA; D003513:Cycloheximide; C471606:RAD6 protein, S cerevisiae; D044763:Ubiquitin-Conjugating Enzymes; D001616:beta-Galactosidase; D015032:Zinc