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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
28
pubmed:dateCreated
1989-10-25
pubmed:abstractText
Virus inducible elements (IE) in promoters of mouse alpha-interferon and human beta 1-interferon genes contain multiple copies of the hexanucleotide sequence AGT-GAA or its variants which are also found in the interferon-stimulated response element of genes transcriptionally induced by interferon. We have examined the similarities between virus and interferon induction of gene expression and the role of AGTGAA and AAT-GAA hexamers in these responses. Hybrid plasmids were constructed by inserting the IE region, the alpha 4 promoter, or the multiple copies of AGTGAA or AAT-GAA 5' to the inactive-45 human immunodeficiency-chloramphenicol acetyltransferase hybrid gene, and their inducible expression was studied in a transient expression assay. In L-cells, multiple hexamers were efficiently induced both by infection with Newcastle disease virus and by interferon treatment; while the alpha 4 promoter and the IE inducible region were induced predominantly by virus rather than by interferon. In order to dissociate the effect of virus and endogenous interferon on the induction process, we examined the gene expression in Vero cells, which have undergone homozygous deletion of type 1 interferon genes, and in VNPT-159 cells, which were derived from Vero cells by insertion of an inducible human interferon beta 1 gene. The results show that while the alpha 4 promoter was efficiently induced only by virus in both cell types, the constructs containing shorter segments of the IE were induced by both virus and interferon in Vero cells. However, the inducibility by interferon was not detected in VNPT-159 cells, suggesting that the presence of endogenous interferon suppresses interferon-induced expression of hexanucleotide repeats and the short inducible region. In contrast, virus inducibility of endogenous interferon-stimulated genes, ISG-15 and ISG-54, was about 100-fold more efficient in VNPT-159 cells than in Vero cells, suggesting that this induction is largely mediated through synthesis of endogenous interferon. Hence, endogenous interferon may play a role in the autoregulation of both interferon genes and interferon-stimulated genes.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
264
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
16658-66
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:2550451-Animals, pubmed-meshheading:2550451-Base Sequence, pubmed-meshheading:2550451-Cells, Cultured, pubmed-meshheading:2550451-Gene Expression Regulation, pubmed-meshheading:2550451-Genes, pubmed-meshheading:2550451-Humans, pubmed-meshheading:2550451-Interferon Type I, pubmed-meshheading:2550451-L Cells (Cell Line), pubmed-meshheading:2550451-Mice, pubmed-meshheading:2550451-Molecular Sequence Data, pubmed-meshheading:2550451-Parainfluenza Virus 1, Human, pubmed-meshheading:2550451-Plasmids, pubmed-meshheading:2550451-Poly I-C, pubmed-meshheading:2550451-Promoter Regions, Genetic, pubmed-meshheading:2550451-RNA, Messenger, pubmed-meshheading:2550451-Simian virus 40, pubmed-meshheading:2550451-Transcription, Genetic, pubmed-meshheading:2550451-Transfection, pubmed-meshheading:2550451-Vero Cells
pubmed:year
1989
pubmed:articleTitle
Virus infection and interferon can activate gene expression through a single synthetic element, but endogenous genes show distinct regulation.
pubmed:affiliation
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine Oncology Center, Baltimore, Maryland 21205.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't