Technological advances in the study of HLA-DRA promoter regulation: extending the functions of CIITA, Oct-1, Rb, and RFX.
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.
Niesen
Melissa I
MI
Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, FL 33612, USA.
Osborne
Aaron R
AR
Lagor
William R
WR
Zhang
Harry
H
Kazemfar
Kristy
K
Ness
Gene C
GC
Blanck
George
G
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005822:Genetic Vectors; D008156:Luciferases / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D050811:Octamer Transcription Factor-1 / Q000235:genetics / Q000502:physiology*; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D016160:Retinoblastoma Protein / Q000235:genetics / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014162:Transfection
D004268:DNA-Binding Proteins; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D050811:Octamer Transcription Factor-1; C494166:Pou2f1 protein, mouse; D000071701:Regulatory Factor X Transcription Factors; D016160:Retinoblastoma Protein; D015534:Trans-Activators; D014157:Transcription Factors; D008156:Luciferases