Retinoblastoma protein expression facilitates chromatin remodeling at the HLA-DRA promoter.
The major histocompatibility complex (MHC) class II genes encode a series of heterodimeric cell surface glycoproteins that bind peptide antigen. The MHC class II/peptide complex is bound by the T-cell receptor of CD4(+) T cells, thereby stimulating an immune response. The MHC class II genes are coordinately regulated by conserved promoter elements and are inducible by IFN-gamma. Furthermore, IFN-gamma induction of the MHC class II genes in solid human tumor lines requires retinoblastoma protein (Rb). In vivo footprinting analyses of the HLA-DRA gene, which encodes the heavy chain subunit of the human MHC class II molecule, HLA-DR, revealed that Rb facilitates occupancy of multiple HLA-DRA promoter elements. Detecting the effect of Rb on HLA-DRA promoter occupancy in vivo required IFN-gamma treatment. However, use of a variation on the in vivo footprinting technique, nuclei footprinting, which assays for promoter occupancy in isolated nuclei, revealed that expression of Rb facilitates promoter occupancy even in the absence of IFN-gamma. These results indicate that expression of Rb leads to modification of the chromatin environment of the HLA-DRA promoter independently of transcription.
Osborne
A
A
Department of Biochemistry and Molecular Biology and Institute for Biomolecular Science, University of South Florida College of Medicine, Tampa, FL 33612, USA.
Tschickardt
M
M
Blanck
G
G
D002843:Chromatin / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D018983:DNA Footprinting; D004273:DNA, Neoplasm / Q000235:genetics; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000235:genetics*; D059805:HLA-DR alpha-Chains; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D016160:Retinoblastoma Protein / Q000502:physiology*; D014407:Tumor Cells, Cultured
D002843:Chromatin; D004273:DNA, Neoplasm; D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D016160:Retinoblastoma Protein; D007371:Interferon-gamma