PMID- 11160721
OWN - NLM
STAT- MEDLINE
DCOM- 20010329
LR  - 20181113
IS  - 0022-538X (Print)
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Linking)
VI  - 75
IP  - 5
DP  - 2001 Mar
TI  - Type B leukemogenic virus has a T-cell-specific enhancer that binds AML-1.
PG  - 2174-84
AB  - Type B leukemogenic virus (TBLV) induces rapidly appearing T-cell tumors in mice. 
      TBLV is highly related to mouse mammary tumor virus (MMTV) except that TBLV long 
      terminal repeats (LTRs) have a deletion of negative regulatory elements and a 
      triplication of sequences flanking the deletion. To determine if the LTR 
      triplication represents a viral enhancer element, we inserted the triplication 
      upstream and downstream in either orientation relative to the thymidine kinase 
      promoter linked to the luciferase gene. These experiments showed that 
      upregulation of reporter gene activity by the TBLV triplication was relatively 
      orientation independent, consistent with the activity of eukaryotic enhancer 
      elements. TBLV enhancer activity was observed in T-cell lines but not in 
      fibroblasts, B cells, or mammary cells, suggesting that enhancer function is cell 
      type dependent. To analyze the transcription factor binding sites that are 
      important for TBLV enhancer function, we prepared substitution mutations in a 
      reconstituted C3H MMTV LTR that recapitulates the deletion observed in the TBLV 
      LTR. Transient transfections showed that a single mutation (556M) decreased TBLV 
      enhancer activity at least 20-fold in two different T-cell lines. This mutation 
      greatly diminished AML-1 (recently renamed RUNX1) binding in gel shift assays 
      with a mutant oligonucleotide, whereas AML-1 binding to a wild-type TBLV oligomer 
      was specific, as judged by competition and supershift experiments. The 556 
      mutation also reduced TBLV enhancer binding of two other protein complexes, 
      called NF-A and NF-B, that did not appear to be related to c-Myb or Ets. AML-1 
      overexpression in a mammary cell line enhanced expression from the TBLV LTR 
      approximately 30-fold. These data suggest that binding of AML-1 to the TBLV 
      enhancer, likely in combination with other factors, is necessary for optimal 
      enhancer function.
FAU - Mertz, J A
AU  - Mertz JA
AD  - Section of Molecular Genetics and Microbiology and Institute for Cellular and 
      Molecular Biology, The University of Texas at Austin, Austin, Texas 78712, USA.
FAU - Mustafa, F
AU  - Mustafa F
FAU - Meyers, S
AU  - Meyers S
FAU - Dudley, J P
AU  - Dudley JP
LA  - eng
GR  - P01 CA077760/CA/NCI NIH HHS/United States
GR  - P01 CA77760/CA/NCI NIH HHS/United States
GR  - R01 CA34780/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Core Binding Factor Alpha 2 Subunit)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (RUNX1 protein, human)
RN  - 0 (Runx1 protein, mouse)
RN  - 0 (Runx1 protein, rat)
RN  - 0 (Transcription Factors)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - Core Binding Factor Alpha 2 Subunit
MH  - DNA-Binding Proteins/*metabolism
MH  - Enhancer Elements, Genetic/genetics/*physiology
MH  - Genes, Reporter
MH  - Humans
MH  - Jurkat Cells
MH  - Luciferases/genetics/metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Plasmids/genetics
MH  - *Proto-Oncogene Proteins
MH  - Rats
MH  - Retroviridae/*genetics/physiology
MH  - T-Lymphocytes/physiology/*virology
MH  - Terminal Repeat Sequences/*genetics/physiology
MH  - Transcription Factors/*metabolism
MH  - Transcription, Genetic
MH  - Transfection
PMC - PMC114801
EDAT- 2001/02/13 11:00
MHDA- 2001/04/03 10:01
PMCR- 2001/03/01
CRDT- 2001/02/13 11:00
PHST- 2001/02/13 11:00 [pubmed]
PHST- 2001/04/03 10:01 [medline]
PHST- 2001/02/13 11:00 [entrez]
PHST- 2001/03/01 00:00 [pmc-release]
AID - 1899 [pii]
AID - 10.1128/JVI.75.5.2174-2184.2001 [doi]
PST - ppublish
SO  - J Virol. 2001 Mar;75(5):2174-84. doi: 10.1128/JVI.75.5.2174-2184.2001.