Transcriptional activity of core binding factor α (AML1) and β subunits on murine leukemia virus enhancer cores

A. L. Zaiman, A. F. Lewis, B. E. Crute, N. A. Speck, Jack Lenz

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Core binding factor (CBF), also known as polyomavirus enhancer-binding protein 2 and SL3 enhancer factor 1, is a mammalian transcription factor that binds to an element termed the core within the enhancers of the murine leukemia virus family of retroviruses. The core elements of the SL3 virus are important genetic determinants of the ability of this virus to induce T-cell lymphomas and the transcriptional activity of the viral long terminal repeat in T lymphocytes. CBF consists of two subunits, a DNA binding subunit, CBF α, and a second subunit, CBF β, that stimulates the DNA binding activity of CBF α. One of the genes that encodes a CBF α subunit is AML1, also called Cbfα2. This locus is rearranged by chromosomal translocations in human myeloproliferative disorders and leukemias. An exogenously expressed Cbfα2- encoded subunit (CBFα2-451) stimulated transcription from the SL3 enhancer in P19 and HeLa cells. Activity was mediated through the core elements. Three different isoforms of CBF β were also tested for transcriptional activity on the SL3 enhancer. The longest form, CBF β-187, increased the transcriptional stimulation by CBFα2-451 twofold in HeLa cells, although it had no effect in P19 cells. Transcriptional activation by CBF β required binding to the CBF α subunit, as a form of CBF β that lacked binding ability, CBF β-148, failed to increase activity. These results indicated that at least in certain cell types, the maximum activity of CBF required both subunits. They also provided support for the hypothesis that CBF is a factor in T lymphocytes that is responsible for recognition of the SL3 cores. We also examined whether CBF could distinguish a 1-bp difference between the enhancer core of SL3 and the core of the nonleukemogenic virus, Akv. This difference strongly affects transcription in T cells and leukemogenicity of SL3. However, no combination of CBF α and CBF β subunits that we tested was able to distinguish the 1-bp difference in transcription assays. Thus, a complete understanding of how T cells recognize the SL3 core remains to be elucidated.

Original languageEnglish (US)
Pages (from-to)2898-2906
Number of pages9
JournalJournal of Virology
Volume69
Issue number5
StatePublished - 1995

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Core Binding Factors
Murine leukemia virus
Murine Leukemia Viruses
T-lymphocytes
transcription (genetics)
viruses
Retroviridae
Polyomavirus
cells
terminal repeat sequences
binding capacity
DNA
transcriptional activation
lymphoma
leukemia
binding proteins
transcription factors
T-Lymphocytes
loci
Viruses

ASJC Scopus subject areas

  • Immunology

Cite this

Transcriptional activity of core binding factor α (AML1) and β subunits on murine leukemia virus enhancer cores. / Zaiman, A. L.; Lewis, A. F.; Crute, B. E.; Speck, N. A.; Lenz, Jack.

In: Journal of Virology, Vol. 69, No. 5, 1995, p. 2898-2906.

Research output: Contribution to journalArticle

Zaiman, A. L. ; Lewis, A. F. ; Crute, B. E. ; Speck, N. A. ; Lenz, Jack. / Transcriptional activity of core binding factor α (AML1) and β subunits on murine leukemia virus enhancer cores. In: Journal of Virology. 1995 ; Vol. 69, No. 5. pp. 2898-2906.
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AB - Core binding factor (CBF), also known as polyomavirus enhancer-binding protein 2 and SL3 enhancer factor 1, is a mammalian transcription factor that binds to an element termed the core within the enhancers of the murine leukemia virus family of retroviruses. The core elements of the SL3 virus are important genetic determinants of the ability of this virus to induce T-cell lymphomas and the transcriptional activity of the viral long terminal repeat in T lymphocytes. CBF consists of two subunits, a DNA binding subunit, CBF α, and a second subunit, CBF β, that stimulates the DNA binding activity of CBF α. One of the genes that encodes a CBF α subunit is AML1, also called Cbfα2. This locus is rearranged by chromosomal translocations in human myeloproliferative disorders and leukemias. An exogenously expressed Cbfα2- encoded subunit (CBFα2-451) stimulated transcription from the SL3 enhancer in P19 and HeLa cells. Activity was mediated through the core elements. Three different isoforms of CBF β were also tested for transcriptional activity on the SL3 enhancer. The longest form, CBF β-187, increased the transcriptional stimulation by CBFα2-451 twofold in HeLa cells, although it had no effect in P19 cells. Transcriptional activation by CBF β required binding to the CBF α subunit, as a form of CBF β that lacked binding ability, CBF β-148, failed to increase activity. These results indicated that at least in certain cell types, the maximum activity of CBF required both subunits. They also provided support for the hypothesis that CBF is a factor in T lymphocytes that is responsible for recognition of the SL3 cores. We also examined whether CBF could distinguish a 1-bp difference between the enhancer core of SL3 and the core of the nonleukemogenic virus, Akv. This difference strongly affects transcription in T cells and leukemogenicity of SL3. However, no combination of CBF α and CBF β subunits that we tested was able to distinguish the 1-bp difference in transcription assays. Thus, a complete understanding of how T cells recognize the SL3 core remains to be elucidated.

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