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PMID: 7799921 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Identification of the rel family members required for virus induction of the human beta interferon gene.

Molecular and cellular biology ·Vol. 15 ·No. 1 ·1995-01-00 ·Pages 152-64

Thanos D, Maniatis T

Abstract

We have carried out experiments to determine which members of the rel family of transcription factors are involved in virus induction of the beta interferon (IFN-beta) gene. First, we examined the inducibility of artificial DNA binding sites that preferentially interact with different homo- or heterodimeric combinations of rel proteins in vitro. We found that only those sites capable of binding the p50/p65 heterodimer are virus inducible. Second, we analyzed a series of mutant rel DNA-binding sites in the context of the intact IFN-beta promoter. We found a correlation between (i) sites capable of binding both the p50/p65 heterodimer and the high-mobility-group protein HMG I(Y) and (ii) virus inducibility. Third, cotransfection of the IFN-beta gene enhancer/promoter with plasmids capable of expressing several different rel proteins revealed that only the combination of p50 and p65 efficiently activated transcription. Finally, we have used antibodies directed against different rel proteins to show that virus-inducible protein-DNA complexes assembled on the IFN-beta enhancer in vitro contain both p50 and p65. We conclude that the p50/p65 heterodimer is responsible for the NF-kappa B-dependent activation of the IFN-beta gene promoter in response to virus infection.

MeSH Terms
Base Sequence Cell Line Gene Expression Regulation, Viral Humans In Vitro Techniques Interferon-beta/genetics Molecular Sequence Data NF-kappa B/physiology Oligodeoxyribonucleotides/chemistry Promoter Regions, Genetic RNA, Messenger/genetics Virus Diseases/genetics
Chemicals
NF-kappa B Oligodeoxyribonucleotides RNA, Messenger Interferon-beta
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Thanos D
Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138.
Maniatis T
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
Published
1995-01-00
Pages
152-64
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC231925
Subset
IM
Grants
NIAID NIH HHS · AI 20642 · United States
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