Regulation of c-maf gene expression by Pax6 in cultured cells

Nucleic Acids Res. 2001 Mar 1;29(5):1228-37. doi: 10.1093/nar/29.5.1228.


c-Maf is a bZip transcription factor expressed in developmental and cellular differentiation processes. Recently, a c-maf knockout mouse model, showing abnormal lens development, has been reported. In order to study the regulation mechanisms of c-maf gene expression during the differentiation process we have cloned and functionally characterized the rat c-maf (maf-2) gene. The rat c-maf gene is an intronless gene, covering a length of 3.5 kb. Transient transfection analysis of the 5'-flanking region of the c-maf gene using luciferase as the reporter gene shows that Pax6, a master transcription factor for lens development, strongly activates the c-maf promoter construct. Endogenous c-maf is also activated by the Pax6 expression vector. Electrophoresis mobility shift assay and DNase I footprinting analysis show that at least three Pax6-binding sites are located in the 5'-flanking and 5'-non-coding regions of the rat c-maf gene. The c-maf gene was also markedly activated by its own product, c-Maf, through the MARE (Maf recognition element), suggesting that a positive autoregulatory mechanism controls this gene. In situ hybridization histochemical detection of Pax6 and c-Maf in the E14 lens showed that both mRNAs are expressed in the lens equator where lens epithelial cells are differentiating to lens fiber cells. These results suggest that a Pax6/c-Maf transcription factor cascade is working in lens development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cloning, Molecular
  • DNA / chemistry
  • DNA / genetics
  • DNA / metabolism
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism
  • Eye Proteins
  • Gene Expression Regulation
  • Genes / genetics
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Luciferases / genetics
  • Luciferases / metabolism
  • Molecular Sequence Data
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Promoter Regions, Genetic / genetics
  • Protein Binding
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-maf
  • Rats
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Regulatory Sequences, Nucleic Acid / genetics
  • Repressor Proteins
  • Restriction Mapping
  • Sequence Analysis, DNA
  • Sequence Deletion
  • Transcription, Genetic
  • Transfection


  • DNA-Binding Proteins
  • Eye Proteins
  • Homeodomain Proteins
  • Maf protein, rat
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors
  • Pax6 protein, mouse
  • Pax6 protein, rat
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-maf
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • DNA
  • Luciferases

Associated data

  • GENBANK/AY005471