Silencer activity in the interferon-A gene promoters.
Interferon-A (IFN-A) differential gene expression is modulated by a complex interplay between cis-acting DNA elements and the corresponding specific trans-regulating factors. Substitutions in the proximal virus-responsive element of the interferon-A (IFN-A) promoters contribute to their differential gene expression. The 5' distal silencing region in the weakly virus-inducible murine IFN-A11 gene has been previously delimited. DNase I footprinting experiments and transient gene expression assays demonstrate identical silencing activity in equivalent regions of the genes for IFN-A11 and IFN-A4 promoters. A minimal 20-mer distal negative regulatory element (DNRE) in both promoters is necessary and sufficient for the silencing and a region in the highly inducible IFN-A4 promoter located between the silencer and the virus-responsive element overrides the silencer activity. Mutations in the central region of the DNRE, causing derepression, also altered the formation of one of the two major DNA-protein complexes. One of these contains a protein related to or identical to the high mobility group I(Y) proteins, while the other complex contains a major protein present in uninduced and virus-induced cells with a molecular mass of 38 kDa, which may be related to the silencer activity. Similar DNREs are present in other virus-uninducible IFN-A promoters, and these data suggest that a common silencer may mediate the transcriptional repression in different genes of this family.
Lopez
S
S
Laboratoire de Régulation de l'Expression des Gènes Eucaryotes, CNRS, UPR 37, UFR Biomédicale des Saints-Pères, Université René Descartes, 45 Rue des Saints-Pères, 75270 Paris Cedex 06, France.
Reeves
R
R
Island
M L
ML
Bandu
M T
MT
Christeff
N
N
Doly
J
J
Navarro
S
S
D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA; D018983:DNA Footprinting; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000378:metabolism; D006801:Humans; D016898:Interferon-alpha / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012045:Regulatory Sequences, Nucleic Acid; D014158:Transcription, Genetic; D014162:Transfection
D006609:High Mobility Group Proteins; D016898:Interferon-alpha; D009687:Nuclear Proteins; D004247:DNA; D016660:NAD(P)H Dehydrogenase (Quinone)