Characterization of the promoter of human leukocyte-specific transcript 1 - A small gene with a complex pattern of alternative transcripts

Citation
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
Citations number
31
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
275
Issue
44
Year of publication
2000
Pages
34597 - 34608
Database
ISI
SICI code
0021-9258(20001103)275:44<34597:COTPOH>2.0.ZU;2-0
Abstract
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.