The HAP2,3,4 transcriptional activator is required for derepression of the yeast citrate synthase gene, CIT1

Mol Microbiol. 1994 Jul;13(1):119-31. doi: 10.1111/j.1365-2958.1994.tb00407.x.


The yeast nuclear gene CIT1 encodes mitochondrial citrate synthase, which catalyses the first and rate-limiting step of the tricarboxylic acid (TCA) cycle. Transcription of CIT1 is subject to glucose repression. Mutations in HAP2, HAP3 or HAP4 block derepression of a CIT1-lacZ gene fusion. The HAP2,3,4 transcriptional activator also activates nuclear genes encoding components of the mitochondrial electron transport chain, and thus it co-ordinates derepression of two major mitochondrial functions. Two DNA sequences resembling the consensus HAP2,3,4-binding site (ACCAATNA) are located at approximately -310 and -290, upstream of the CIT1 coding sequence. Deletion and mutation analysis indicates that the -290 element is critical for activation by HAP2,3,4. Glucose-repressed expression of CIT1 is largely independent of HAP2,3,4, is repressed by glutamate, and requires a DNA sequence between -367 and -348. Evidence is presented for a second HAP2,3,4-independent activation element located just upstream and overlapping the -290 HAP2,3,4 element.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Base Sequence
  • CCAAT-Binding Factor*
  • Citrate (si)-Synthase / biosynthesis*
  • Citrate (si)-Synthase / genetics
  • Consensus Sequence
  • DNA, Fungal / genetics
  • Fungal Proteins / genetics
  • Fungal Proteins / physiology*
  • Genes, Fungal
  • Molecular Sequence Data
  • Mutagenesis
  • Polymerase Chain Reaction
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Sequence Deletion
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transcription, Genetic


  • CCAAT-Binding Factor
  • DNA, Fungal
  • Fungal Proteins
  • HAP4 protein, S cerevisiae
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors
  • Citrate (si)-Synthase

Associated data

  • GENBANK/X63746