Technological advances in the study of HLA-DRA promoter regulation: Extending the functions of CIITA, Oct-1, Rb, and RFX
Department of Molecular Medicine, College of Medicine, University of South Florida, Tampa, FL 33612, USA
* Corresponding address. Tel: +1-813-974-9585; E-mail: gblanck{at}health.usf.edu
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Abstract |
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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.
Keywords HLA-DR; class II transactivator; Oct-1; retinoblastoma protein; regulatory factor-X
Received: September 3, 2008; Accepted: December 10, 2008
Current address: Institute for Translational Medicine and Therapeutics, School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA