Xf. Yu et Sm. Weissman, Characterization of the promoter of human leukocyte-specific transcript 1 - A small gene with a complex pattern of alternative transcripts, J BIOL CHEM, 275(44), 2000, pp. 34597-34608
The gene for the human leukocyte-specific transcript 1 (LST1) encodes a sma
ll protein that modulates immune responses and cellular morphogenesis. The
LST1 transcripts are expressed at high levels in dendritic cells. Because o
f the complex splicing pattern, use of alternative 5'-untranslated exons, a
nd a biologically interesting pattern of expression of LST1 mRNA, we studie
d the human LST1 gene promoter and regulatory elements. We identified an ad
ditional upstream 5'-untranslated exon in U937 monocytic cells. Transient t
ransfection studies demonstrated that the combination of regions from -1363
to -621 with -112 to -54, relative to the translation start codon, produce
d the highest level of transcripts from among the various constructs tested
, but the pattern of transcripts produced was only a subset of those produc
ed from the endogenous gene. DNase I footprinting analysis and electrophore
tic mobility shift assays showed that oligonucleotide probes corresponding
to three regions, -1171 to -1142 (BI), -1136 to -1111 (BII), and -783 to -7
51 (BTV), bound proteins in U937 nuclear extracts. Competition and supershi
ft electrophoretic mobility shift assay did not identify any known transcri
ption factors responsible for BII probe binding. These studies suggest that
a novel DNA-binding site and interaction of multiple regulatory elements m
ay be involved in mediating the expression of the various forms of LST1 mRN
A.