The nuclear factor YY1 suppresses the human gamma interferon promoter through two mechanisms: inhibition of AP1 binding and activation of a silencer element.
Our group has previously reported that the nuclear factor Yin-Yang 1 (YY1), a ubiquitous DNA-binding protein, is able to interact with a silencer element (BE) in the gamma interferon (IFN-gamma) promoter region. In this study, we demonstrated that YY1 can directly inhibit the activity of the IFN-gamma promoter by interacting with multiple sites in the promoter. In cotransfection assays, a YY1 expression vector significantly inhibited IFN-gamma promoter activity. Mutation of the YY1 binding site in the native IFN-gamma promoter was associated with an increase in the IFN-gamma promoter activity. Analysis of the DNA sequences of the IFN-gamma promoter revealed a second functional YY1 binding site (BED) that overlaps with an AP1 binding site. In this element, AP1 enhancer activity was suppressed by YY1. Since the nuclear level of YY1 does not change upon cell activation, our data support a model that the nuclear factor YY1 acts to suppress basal IFN-gamma transcription by interacting with the promoter at multiple DNA binding sites. This repression can occur through two mechanisms: (i) cooperation with an as-yet-unidentified AP2-like repressor protein and (ii) competition for DNA binding with the transactivating factor AP1.
Ye
J
J
Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute-Frederick Cancer Research and Developmental Center, Maryland 21702-1201, USA.
Cippitelli
M
M
Dorman
L
L
Ortaldo
J R
JR
Young
H A
HA
D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D007694:Killer Cells, Natural / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000473:pathology; D008957:Models, Genetic; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D012097:Repressor Proteins / Q000502:physiology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured; D050986:YY1 Transcription Factor
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D007371:Interferon-gamma; D004247:DNA