Technological advances in the study of HLA-DRA promoter regulation: extending the functions of CIITA, Oct-1, Rb, and RFX

Acta Biochim Biophys Sin (Shanghai). 2009 Mar;41(3):198-205. doi: 10.1093/abbs/gmp002.


Several advances were established in examining the interaction of transcriptional factors with the HLA-DRA promoter. First, hydrodynamic injection was used to demonstrate the activation of the promoter by class II transactivator in a live mouse. Second, the Oct-1 DNA-binding site in the HLA-DRA promoter is a negative element in many cells, but here we show that Oct-1 activates the promoter independently of the Oct-1-binding site. Third, the retinoblastoma (Rb) protein is required for the induction of the endogenous HLA-DRA gene, due to a poorly understood, pleiotropic effect on the Oct-1 and YY1 repressive functions at the HLA-DRA promoter. There has never been an indication that direct promoter activation, by Rb, is possible. Here, we report that the first HLA-DRA intron has an Rb-responsive element, as indicated by a transient transfection/promoter reporter assay. Finally, RFX activates a methylated version of an HLA-DRA promoter reporter construct, consistent with the role of RFX in rescuing the expression of the methylated, endogenous HLA-DRA gene. Here, we report that this RFX function is not limited to a specific RFX-binding sequence or to the HLA-DRA promoter. These advances provide bases for novel investigations into the function of the major histocompatibility class II promoter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / genetics
  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / physiology*
  • Genetic Vectors
  • Luciferases / analysis
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Octamer Transcription Factor-1 / genetics
  • Octamer Transcription Factor-1 / physiology*
  • Promoter Regions, Genetic
  • Regulatory Factor X Transcription Factors
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / physiology*
  • Transfection


  • DNA-Binding Proteins
  • MHC class II transactivator protein
  • Nuclear Proteins
  • Octamer Transcription Factor-1
  • Pou2f1 protein, mouse
  • Regulatory Factor X Transcription Factors
  • Retinoblastoma Protein
  • Trans-Activators
  • Transcription Factors
  • Luciferases