Co-ordinate regulation of lactate metabolism genes in yeast: the role of the lactate permease gene JEN1

Mol Genet Genomics. 2002 Jan;266(5):838-47. doi: 10.1007/s00438-001-0604-y. Epub 2001 Nov 7.

Abstract

In the yeast Saccharomyces cerevisiae, the first step in lactate metabolism is its transport across the plasma membrane, a proton symport process mediated by the product of the gene JEN1. Under aerobic conditions, the expression of JEN1 is regulated by the carbon source: the gene is repressed by glucose and induced by non-fermentable substrates. JEN1 expression is also controlled by oxygen availability, but is unaffected by the absence of haem biosynthesis. JEN1 is negatively regulated by the repressors Mig1p and Mig2p, and requires Cat8p for full derepression. In this report we demonstrate that, in addition to these regulators, the Hap2/3/4/5 complex interacts specifically with a CAAT-box element in the JEN1 promoter, and acts to derepress JEN1 expression. We also provide evidence for transcriptional stimulation of JEN1 by the protein kinase Snf1p. Data are presented which provide a better understanding of the molecular mechanisms implicated in the co-regulation of genes involved in the metabolism of lactate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aerobiosis
  • Base Sequence
  • CCAAT-Binding Factor / genetics
  • CCAAT-Binding Factor / metabolism
  • Carbon / metabolism
  • DNA, Fungal / genetics
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Gene Expression Regulation, Fungal
  • Genes, Fungal*
  • Heme / genetics
  • Heme / metabolism
  • L-Lactate Dehydrogenase / biosynthesis
  • Lactic Acid / metabolism*
  • Monocarboxylic Acid Transporters / genetics*
  • Promoter Regions, Genetic
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism
  • Symporters / genetics*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • CAT8 protein, S cerevisiae
  • CCAAT-Binding Factor
  • DNA, Fungal
  • Fungal Proteins
  • JEN1 protein, S cerevisiae
  • Monocarboxylic Acid Transporters
  • Saccharomyces cerevisiae Proteins
  • Symporters
  • Trans-Activators
  • Lactic Acid
  • Heme
  • Carbon
  • L-Lactate Dehydrogenase
  • SNF1-related protein kinases
  • Protein-Serine-Threonine Kinases