Insertion of an intracisternal A particle within the 5'-regulatory region of a gene encoding folate-binding protein in L1210 leukemia cells in response to low folate selection. Association with increased protein expression.
We have previously described a subline of L1210 murine leukemia cells (LL1) selected in a low level of 5-formyltetrahydrofolate which overexpresses a membrane-bound folate-binding protein (FBP1) and exhibits a rearrangement at the locus encoding this protein. Genomic clones containing the entire FBP1-encoding DNA from both L1210 and LL1 were isolated and characterized. Sequence analysis indicates that, with exception of the 5'-region, the FBP1-encoding locus in both cell lines is identical. The rearrangement in LL1 results from the insertion of an intracisternal A particle (IAP) in the head-to-head (antisense) orientation 72 base pairs (bp) upstream of the FBP1 ATG start codon. The IAP likely provides an alternative promoter for FBP1 expression which may produce a novel transcript with enhanced stability. Presence of the IAP appears to inactivate or relocate normal cis-acting regulatory sequences as expression of the FBP1 transcript in LL1 is not regulated by the folate status of the cell.
Brigle
K E
KE
Department of Medicine, Virginia Commonwealth University, Medical College of Virginia, Richmond 23298.
Westin
E H
EH
Houghton
M T
MT
Goldman
I D
ID
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D058973:Folate Receptors, GPI-Anchored; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D005796:Genes; D007426:Genes, Intracisternal A-Particle; D007939:Leukemia L1210 / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011956:Receptors, Cell Surface
D002352:Carrier Proteins; D004273:DNA, Neoplasm; D058973:Folate Receptors, GPI-Anchored; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D011956:Receptors, Cell Surface