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Oncogene
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25 September 1997, Volume 15, Issue 13, Pages 1535 – 1544 |
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| Article |
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Transcriptional regulation of OCI-5/Glypican 3: elongation control of confluence-dependent induction
M Li1,4, R Pullano1, HL Yang2, HK Lee1, NG Miyamoto3, J Filmus2 & RN Buick5 1Ontario Cancer Institute/Princess Margaret Hospital and Department of Medical Biophysics, University of Toronto, 610 University Ave. Tononto, M5G 2M9 2Division of Cancer Research, Sunnybrook Health Science Centre and Department of Medical Biophysics, University of Toronto, Toronto, Canada 3Department of Immunology, Berlex Biosciences, 15049 San Pablo Avenue, Richmond, California 94804, USA4Author for correspondence 5Deceased July 20, 1996 |
| Keywords |
| proteoglycan;
SGBS;
intestine;
promoter;
elongation;
confluence |
| Abstract |
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, |
Received 20 November, 96; Revised 2 June, 97; Accepted 2 June, 97
-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.