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

Kevin E. Brigle, Eric H. Westin, Micah T. Houghton, I. David Goldman

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18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)22351-22355
Number of pages5
JournalJournal of Biological Chemistry
Volume267
Issue number31
StatePublished - Nov 5 1992
Externally publishedYes

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Leukemia L1210
Gene encoding
Nucleic Acid Regulatory Sequences
Folic Acid
Carrier Proteins
Initiator Codon
Leucovorin
Base Pairing
Genes
Sequence Analysis
Proteins
Clone Cells
Cells
Membranes
Cell Line
DNA

ASJC Scopus subject areas

  • Biochemistry

Cite this

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title = "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",
abstract = "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.",
author = "Brigle, {Kevin E.} and Westin, {Eric H.} and Houghton, {Micah T.} and Goldman, {I. David}",
year = "1992",
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T1 - 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

T2 - Association with increased protein expression

AU - Brigle, Kevin E.

AU - Westin, Eric H.

AU - Houghton, Micah T.

AU - Goldman, I. David

PY - 1992/11/5

Y1 - 1992/11/5

N2 - 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.

AB - 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.

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