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PMID: 8764076 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Transcriptional activation of a retrovirus enhancer by CBF (AML1) requires a second factor: evidence for cooperativity with c-Myb.

Journal of virology ·Vol. 70 ·No. 8 ·1996-08-00 ·Pages 5618-29

Zaiman AL, Lenz J

Abstract

Transcriptional enhancer sequences within the long terminal repeats (LTRs) of murine leukemia viruses are the primary genetic determinants of the tissue specificity and potency of the oncogenic potential of these retroviruses. SL3-3 (SL3) is a murine leukemia virus that induces T-cell lymphomas. The LTR enhancer of this virus contains two binding sites for the transcription factor CBF (also called AML1 and PEBP2) that flank binding sites for c-Myb and the Ets family of factors. Using cotransfection assays in P19 cells, we report here that CBF and c-Myb cooperatively stimulate transcription from the SL3 LTR. By itself, c-Myb had no stimulatory effect on transcription. However, when cotransfected with a cDNA encoding one form of the alpha subunit of CBF called CBFalpha2-451, a level of transactivation higher than that seen with CBFalpha2-451 alone was detected. The negative regulatory domain near the carboxyl terminus of c-Myb did not affect this activity. Electrophoretic mobility shift assays indicated that CBF and c-Myb bind to DNA independently. Therefore, it appears that the cooperative stimulation of transcription by these factors occurs at a step in the process of transcription after the two factors are bound to the enhancer. Sequences near the carboxyl terminus of CBFalpha2-451 were important for cooperativity with c-Myb, consistent with previous reports that this region contains an activation domain. However, CBFalpha2-451 failed to activate transcription from a version of the SL3 LTR in which the enhancer was replaced with five tandem CBF-binding sites. Thus, it appears that transcriptional activation of the SL3 enhancer by CBF requires that an appropriate heterologous transcription factor be bound to a neighboring site in the regulatory sequences.

MeSH Terms
Animals Base Sequence Binding Sites Cell Line Core Binding Factors DNA-Binding Proteins/genetics Enhancer Elements, Genetic/genetics Leukemia Virus, Murine/genetics Mice Molecular Sequence Data Neoplasm Proteins Proto-Oncogene Proteins/genetics Proto-Oncogene Proteins c-myb Trans-Activators/genetics Transcription Factors/genetics Transcriptional Activation/genetics
Chemicals
Core Binding Factors DNA-Binding Proteins Neoplasm Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-myb Trans-Activators Transcription Factors
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Zaiman A L
Department of Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Lenz J
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.70.8.5618-5629.1996
Published
1996-08-00
Pages
5618-29
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC190522
Subset
IM
Grants
NCI NIH HHS · CA44822 · United States
NCI NIH HHS · CA55337 · United States
NIGMS NIH HHS · GM7288 · United States
External Links
PubMed source DOI: 10.1128/JVI.70.8.5618-5629.1996 PMC Full Text View journal details
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