Complex architecture of major histocompatibility complex class II promoters: reiterated motifs and conserved protein-protein interactions.
The S box (also known as at the H, W, or Z box) is the 5'-most element of the conserved upstream sequences in promoters of major histocompatibility complex class II genes. It is important for their B-cell-specific and interferon gamma-inducible expression. In this study, we demonstrate that the S box represents a duplication of the downstream X box. First, RFX, which is composed of the RFX5-p36 heterodimer that binds to the X box, also binds to the S box and its 5'-flanking sequence. Second, NF-Y, which binds to the Y box and increases interactions between RFX and the X box, also increases the binding of RFX to the S box. Third, RFXs bound to S and X boxes interact with each other in a spatially constrained manner. Finally, we confirmed these protein-protein and protein-DNA interactions by expressing a hybrid RFX5-VP16 protein in cells. We conclude that RFX binds to S and X boxes and that complex interactions between RFX and NF-Y direct B-cell-specific and interferon gamma-inducible expression or major histocompatibility complex class II genes.
Jabrane-Ferrat
N
N
Howard Hughes Medical Institute, University of California San Francisco, 94143, USA.
Fontes
J D
JD
Boss
J M
JM
Peterlin
B M
BM
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D002051:Burkitt Lymphoma / Q000473:pathology; D022762:CCAAT-Enhancer-Binding Proteins; D002461:Cell Line, Transformed; D002522:Chlorocebus aethiops; D004273:DNA, Neoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005802:Genes, MHC Class II; D006684:HLA-DR Antigens / Q000235:genetics*; D059805:HLA-DR alpha-Chains; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000951:Antigens, Neoplasm; D022762:CCAAT-Enhancer-Binding Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D006684:HLA-DR Antigens; D059805:HLA-DR alpha-Chains; D017405:Herpes Simplex Virus Protein Vmw65; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors