Human interferon consensus sequence binding protein is a negative regulator of enhancer elements common to interferon-inducible genes.
The promoter regions of many interferon-inducible genes share a short DNA sequence motif, termed the interferon consensus sequence (ICS) to which several regulatory proteins bind. A murine cDNA which encodes an ICS binding protein has been reported (M-ICSBP). The cloning of the human homologue of ICSBP (H-ICSBP) is described. H-ICSBP shares high sequence homology with its murine cognate. The derived sequence of H-ICSBP reveals restricted homology within the first 120 amino acids to three other interferon regulatory factors, IRF-1, IRF-2, and ISGF3 gamma. Truncated ICSBP lacking the first 33 amino-terminal amino acids fails to bind to the ICS, indicating that at least part of the DNA binding domain is located within the well conserved amino terminus. H-ICSBP is expressed exclusively in cell lines of hematopoietic origin. The results of transient transfection assays carried out either in hematopoietic or nonhematopoietic cells suggest that ICSBP acts as a negative regulatory factor on ICS-containing promoters. Furthermore, either interferon-gamma (IFN-gamma) or IFN-beta can alleviate the repression mediated by ICSBP. Therefore, ICSBP may be involved in maintaining submaximal transcriptional activity of IFN-inducible genes in hematopoietic cells. IFN treatment would then alleviate repression allowing maximal transcriptional activity of these genes.
Weisz
A
A
Department of Food Engineering and Biotechnology, Technion, Haifa, Israel.
Marx
P
P
Sharf
R
R
Appella
E
E
Driggers
P H
PH
Ozato
K
K
Levi
B Z
BZ
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D015723:Gene Library; D006367:HeLa Cells; D006801:Humans; D050835:Interferon Regulatory Factors; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D008168:Lung / Q000502:physiology; D008969:Molecular Sequence Data; D010957:Plasmids; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8
D002352:Carrier Proteins; D015500:Chloramphenicol O-Acetyltransferase; D003513:Cycloheximide; D004247:DNA; D004268:DNA-Binding Proteins; D050835:Interferon Regulatory Factors; D016899:Interferon-beta; D007371:Interferon-gamma; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; D001616:beta-Galactosidase; D000099185:Interferon Regulatory Factor-8