Transcriptional regulation of OCI-5/Glypican 3: elongation control of confluence-dependent induction.
OCI-5/Glypican 3, a member of the glypican family of proteoglycans, is the defective gene in the Simpson-Golabi-Behmel overgrowth syndrome. OCI-5 expression is developmentally regulated in the intestinal epithelium, and the mechanism of its regulation was studied in the rat intestinal epithelial cell line IEC-18. A large induction of OCI-5 transcript and protein was observed at high cell density. Among other glypican family members, kappa-glypican also exhibited a confluence-dependent induction in select cell types. Nuclear run-on analysis indicated that cell-density regulation of OCI-5 occurs at the level of transcription. The rat and mouse OCI-5 promoters were cloned and found to be highly conserved, located within CpG islands and contain regions of alternating purine and pyrimidine residues. No TATA-box or recognizable INR element was observed. Consensus binding sites for AP-2, SP-1, zeste and NF-1/CTF are conserved across human, mouse and rat promoters. 5' deletion mapping of the rat promoter identified regions which enhance and repress promoter activity, with no apparent confluence-dependence or tissue-specificity. Nuclear run-on analysis probing different regions of the gene suggests that elongation control plays a role in the induction of OCI-5 by confluence.
Li
M
M
Ontario Cancer Institute/Princess Margaret Hospital and Department of Medical Biophysics, University of Toronto, Canada.
Pullano
R
R
Yang
H L
HL
Lee
H K
HK
Miyamoto
N G
NG
Filmus
J
J
Buick
R N
RN
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D010441:Peptide Chain Elongation, Translational; D011401:Promoter Regions, Genetic; D011509:Proteoglycans / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D015183:Restriction Mapping; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans; D006497:Heparan Sulfate; D011509:Proteoglycans