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Article: CpG Methylation and Transcription Factors Sp1 and Sp3 Regulate the Expression of the Human Secretin Receptor Gene

TitleCpG Methylation and Transcription Factors Sp1 and Sp3 Regulate the Expression of the Human Secretin Receptor Gene
Authors
Issue Date2004
PublisherEndocrine Society. The Journal's web site is located at http://mend.endojournals.org/
Citation
Molecular Endocrinology, 2004, v. 18 n. 2, p. 471-483 How to Cite?
AbstractThe human secretin receptor (hSR) is an important glycoprotein receptor for regulating the secretion of pancreatic bicarbonate, water, and electrolytes. In this study we investigated the transcriptional regulation of the hSR gene. A minimal 106-bp promoter was identified, and it contains two GC boxes (GC box-A, -240 to -226; and GC box-B, -203 to -194, from the translation start site). EMSA and supershift analyses showed that both GC boxes interact with Sp1 and Sp3 transcription factors. Transient transfection in pancreas-derived human pancreatic ductule carcinoma (PANC)-1 and bovine pancreatic duct-1 cells showed that mutation of either GC box-A or -B reduced the promoter strength by 56-67%, whereas mutation of both GC boxes caused more than 90% reduction of promoter activity. Cotransfections of the hSR promoter with Sp1 and Sp3 expression vectors in Sp-deficient Drosophila SL-2 Schneider cells further demonstrated that the ratio of Sp1 to Sp3 is the key mechanism to modulate hSR gene expression. The methylation statuses of 27 CpG sites within the promoter region (-400 to -151 bp) were assessed in various human pancreas and liver cell lines. The hSR promoter is unmethylated (CAPAN-1, human pancreatic adenocarcinoma) or partially methylated (PANC-1 and HPAC, human pancreatic adenocarcinoma) in hSR-expressing cell lines but is completely methylated in hSR nonexpressing HepG2 cells. Methyltransferase inhibitor 5-aza-2′deoxycytidine increased hSR gene expression level in PANC-1 cells and induced hSR gene expression in HepG2 cells. Together, our study shows that, in addition to Sp1 and Sp3, promoter methylation also plays a role in the regulation of hSR gene expression.
Persistent Identifierhttp://hdl.handle.net/10722/84890
ISSN
2015 Impact Factor: 3.432
2015 SCImago Journal Rankings: 2.195
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPang, RTKen_HK
dc.contributor.authorLee, LTOen_HK
dc.contributor.authorNg, SSMen_HK
dc.contributor.authorYung, WHen_HK
dc.contributor.authorChow, BKCen_HK
dc.date.accessioned2010-09-06T08:58:18Z-
dc.date.available2010-09-06T08:58:18Z-
dc.date.issued2004en_HK
dc.identifier.citationMolecular Endocrinology, 2004, v. 18 n. 2, p. 471-483en_HK
dc.identifier.issn0888-8809en_HK
dc.identifier.urihttp://hdl.handle.net/10722/84890-
dc.description.abstractThe human secretin receptor (hSR) is an important glycoprotein receptor for regulating the secretion of pancreatic bicarbonate, water, and electrolytes. In this study we investigated the transcriptional regulation of the hSR gene. A minimal 106-bp promoter was identified, and it contains two GC boxes (GC box-A, -240 to -226; and GC box-B, -203 to -194, from the translation start site). EMSA and supershift analyses showed that both GC boxes interact with Sp1 and Sp3 transcription factors. Transient transfection in pancreas-derived human pancreatic ductule carcinoma (PANC)-1 and bovine pancreatic duct-1 cells showed that mutation of either GC box-A or -B reduced the promoter strength by 56-67%, whereas mutation of both GC boxes caused more than 90% reduction of promoter activity. Cotransfections of the hSR promoter with Sp1 and Sp3 expression vectors in Sp-deficient Drosophila SL-2 Schneider cells further demonstrated that the ratio of Sp1 to Sp3 is the key mechanism to modulate hSR gene expression. The methylation statuses of 27 CpG sites within the promoter region (-400 to -151 bp) were assessed in various human pancreas and liver cell lines. The hSR promoter is unmethylated (CAPAN-1, human pancreatic adenocarcinoma) or partially methylated (PANC-1 and HPAC, human pancreatic adenocarcinoma) in hSR-expressing cell lines but is completely methylated in hSR nonexpressing HepG2 cells. Methyltransferase inhibitor 5-aza-2′deoxycytidine increased hSR gene expression level in PANC-1 cells and induced hSR gene expression in HepG2 cells. Together, our study shows that, in addition to Sp1 and Sp3, promoter methylation also plays a role in the regulation of hSR gene expression.en_HK
dc.languageengen_HK
dc.publisherEndocrine Society. The Journal's web site is located at http://mend.endojournals.org/en_HK
dc.relation.ispartofMolecular Endocrinologyen_HK
dc.rightsMolecular Endocrinology. Copyright © The Endocrine Society.en_HK
dc.titleCpG Methylation and Transcription Factors Sp1 and Sp3 Regulate the Expression of the Human Secretin Receptor Geneen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0888-8809&volume=18&spage=471&epage=483&date=2004&atitle=CpG+Methylation+and+Transcription+Factors+Sp1+and+Sp3+Regulate+the+Expression+of+the+Human+Secretin+Receptor+Geneen_HK
dc.identifier.emailPang, RTK: rtkpang@hku.hken_HK
dc.identifier.emailLee, LTO: ltolee2@hkucc.hku.hken_HK
dc.identifier.emailNg, SSM: ssmng@hku.hken_HK
dc.identifier.emailChow, BKC: bkcc@hku.hken_HK
dc.identifier.authorityPang, RTK=rp01761en_HK
dc.identifier.authorityLee, LTO=rp00727en_HK
dc.identifier.authorityNg, SSM=rp00767en_HK
dc.identifier.authorityChow, BKC=rp00681en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1210/me.2003-0245en_HK
dc.identifier.pmid14645499-
dc.identifier.scopuseid_2-s2.0-0842269303en_HK
dc.identifier.hkuros85712en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0842269303&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume18en_HK
dc.identifier.issue2en_HK
dc.identifier.spage471en_HK
dc.identifier.epage483en_HK
dc.identifier.isiWOS:000188426400018-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridPang, RTK=7004376636en_HK
dc.identifier.scopusauthoridLee, LTO=8367269000en_HK
dc.identifier.scopusauthoridNg, SSM=7403358718en_HK
dc.identifier.scopusauthoridYung, WH=7103137893en_HK
dc.identifier.scopusauthoridChow, BKC=7102826193en_HK

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