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Transcriptional regulation by Lge1p requires a function independent of its role in histone H2B ubiquitination.

TitleTranscriptional regulation by Lge1p requires a function independent of its role in histone H2B ubiquitination.
Publication TypeJournal Article
Year of Publication2005
AuthorsZhang, X, Kolaczkowska, A, Devaux, F, Panwar, SLata, Hallstrom, TC, Jacq, C, W Moye-Rowley, S
JournalJ Biol Chem
Volume280
Issue4
Pagination2759-70
Date Published2005 Jan 28
ISSN0021-9258
KeywordsATP-Binding Cassette Transporters, beta-Galactosidase, Blotting, Northern, Cell Nucleus, Cycloheximide, DNA, DNA-Binding Proteins, Drug Resistance, Multiple, Gene Expression Regulation, Fungal, Genotype, Histones, Lac Operon, Microscopy, Fluorescence, Mitochondria, Mutation, Oligonucleotide Array Sequence Analysis, Plasmids, Promoter Regions, Genetic, Protein Synthesis Inhibitors, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Ubiquitin, Ubiquitin-Conjugating Enzymes, Zinc
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.

DOI10.1074/jbc.M408333200
Alternate JournalJ. Biol. Chem.
PubMed ID15528187
Grant ListGM49825 / GM / NIGMS NIH HHS / United States