Nucleic Acids Research, Vol 26, Issue 9 2132-2142, Copyright © 1998 by Oxford University Press
H Wang, JF Ross and M Ratnam
The human folate receptor (hFR) type gamma and gamma' are constitutively
secreted proteins that are expressed primarily in hematopoietic tissues and
are potential serum markers for certain hematopoietic malignancies.
hFR-gamma' is a variant of hFR-gamma with a two base deletion in its cDNA
resulting in a truncated polypeptide. The gene encoding hFR-gamma' was
isolated from a placental genomic library. The gene has five exons, four
introns and a 5' flanking sequence which contains multiple putative
regulatory elements. From RNase protection assay and RACE analysis, the
major site of transcriptional initiation was identified at -56 nt.
Systematically deleted fragments in the 5' region of the genomic DNA of
FR-gamma' were ligated into the PGL3Basic plasmid and the reporter
luciferase activity was assayed in cell lysates from transiently
transfected NIH3T3 cells. From those results, putative positive and
negative regulatory regions in the 5' flanking sequences were noted, and a
TATA-less proximal promoter was located between -206 and -22 nt. Gel
mobility shift and supershift analyses as well as mutagenesis experiments
revealed that Sp1 and ets binding elements in the proximal promoter region
confer transcriptional activity. From partial sequencing of genomic DNA,
genomic Southern blots, RACE analysis and RNase protection assays, it
appears that hFR- gamma shares the gene organization of hFR-gamma'. The
results of the analysis of genomic DNA in spleen tissues from several
individuals, were consistent with the interpretation that hFR-gamma and
hFR-gamma' are encoded by a polymorphic gene.
ARTICLES
Structure and regulation of a polymorphic gene encoding folate receptor type gamma/gamma'
Department of Biochemistry and Molecular Biology, Medical College of Ohio, Toledo, OH 43699-0008, USA.
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