Negative control region at the 5' end of murine leukemia virus long terminal repeats.
Using in vitro protein binding and in vivo functional studies, we have identified novel regulatory sequences near the 5' end of murine leukemia virus (MuLV) long terminal repeats (LTRs). These sequences are highly conserved in all MuLV LTRs as well as in feline leukemia virus and gibbon ape leukemia virus LTRs. In this upstream conserved region (UCR), gel retardation assays detected two overlapping but distinct binding sites (UCR-U and UCR-L) for nuclear proteins (UCRF-U and UCRF-L). Three lines of evidence suggest a negative regulatory role for the UCR in viral transcription: (i) an inverse correlation was found between MuLV transcripts and nuclear proteins binding the UCR in the spleens of five different mouse strains; (ii) in vivo treatment of NFS mice with lipopolysaccharide resulted in the induction of splenic viral transcripts and the concomitant disappearance of UCR-binding proteins; and (iii) in mouse L cells transfected with an MuLV LTR linked to the chloramphenicol acetyltransferase (CAT) gene, cotransfected UCR oligonucleotides increased CAT expression, presumably by competing for inhibitory trans-acting factors.
Flanagan
J R
JR
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.
Krieg
A M
AM
Max
E E
EE
Khan
A S
AS
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005809:Genes, Regulator; D005814:Genes, Viral; D007739:L Cells / Q000378:metabolism; D009052:Leukemia Virus, Murine / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid
D004279:DNA, Viral; D009687:Nuclear Proteins