Nucleic Acids Research, Vol 25, Issue 24 5095-5102, Copyright © 1997 by Oxford University Press
A Osborne, M Tschickardt and G Blanck
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.
ARTICLES
Retinoblastoma protein expression facilitates chromatin remodeling at the HLA-DRA promoter
Department of Biochemistry and Molecular Biology and Institute for Biomolecular Science, University of South Florida College of Medicine, Tampa, FL 33612, USA.
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