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PMID: 1895400 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Sequence-specific interaction of the Ets1 protein with the long terminal repeat of the human T-lymphotropic virus type I.

Journal of virology ·Vol. 65 ·No. 10 ·1991-10-00 ·Pages 5513-23

Gitlin SD, Bosselut R, Gégonne A, Ghysdael J, Brady JN

Abstract

We recently demonstrated that members of the c-ets proto-oncogene family, Ets1 and Ets2, are sequence-specific transcriptional activators of the human T-lymphotropic virus type I (HTLV-I) long terminal repeat (LTR). We now report that the HTLV-I LTR contains two distinct Ets1-responsive regions, ERR-1 and ERR-2. Expression of Ets1 with reporter plasmids containing ERR-1 or ERR-2 upstream of a basal promoter resulted in an increase in transcriptional activity. By gel mobility shift assay, the interaction of Ets1 with the downstream ERR-1-binding region was found to be more stable than its interaction with the upstream ERR-2 region. By DNase I footprint, gel mobility shift, and methylation interference analyses, ERR-1 was found to contain two Ets1 binding sites, ERE-A and ERE-B. A recombinant Ets1 protein was found to bind with higher affinity to ERE-A than to ERE-B. Binding of Ets1 to these sites appears to result in a specific and sequential protection of a 37-nucleotide sequence of the HTLV-I LTR from -154 to -118. In view of the high-level expression of Ets1 in lymphoid cells, the c-ets proto-oncogenes encode transcription factors which could play an important role in both basal and Tax1-mediated HTLV-I transcription.

Related Genes
c-ets-1 d-E74 h.PU.1 m-ets-1 n-ets-1
MeSH Terms
Animals Baculoviridae/genetics Base Sequence Binding Sites Cell Line Cell Nucleus/physiology DNA, Viral/genetics,metabolism DNA-Binding Proteins/metabolism HeLa Cells/physiology Human T-lymphotropic virus 1/genetics Humans Immunoblotting Insecta Molecular Sequence Data Multigene Family Mutagenesis, Site-Directed Proto-Oncogene Mas Proto-Oncogene Protein c-ets-1 Proto-Oncogene Proteins/genetics,metabolism Proto-Oncogene Proteins c-ets Proto-Oncogenes Recombinant Proteins/metabolism Repetitive Sequences, Nucleic Acid Sequence Homology, Nucleic Acid Substrate Specificity Transcription Factors
Chemicals
DNA, Viral DNA-Binding Proteins ETS1 protein, human MAS1 protein, human Proto-Oncogene Mas Proto-Oncogene Protein c-ets-1 Proto-Oncogene Proteins Proto-Oncogene Proteins c-ets Recombinant Proteins Transcription Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Gitlin S D
Laboratory of Molecular Virology, National Cancer Institute, Bethesda, Maryland 20892.
Bosselut R
Gégonne A
Ghysdael J
Brady J N
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.65.10.5513-5523.1991
Published
1991-10-00
Pages
5513-23
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC249048
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.65.10.5513-5523.1991 PMC Full Text View journal details
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