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Conference Paper: Transcriptional regulation of the human secretin gene in duodenal and neuronal cells

TitleTranscriptional regulation of the human secretin gene in duodenal and neuronal cells
Authors
Issue Date2005
PublisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/regpep
Citation
The 7th International Symposium on VIP, PACAP and Related Peptides, Rouen, Normandy, France, 11-14 September 2005. In Regulatory Peptides, 2005, v. 130 n. 3, p. 167 How to Cite?
AbstractSecretin is a member of the glucagon/secretin/vasoactive intestinal peptide (VIP) family. To unravel the mechanism that regulates the human secretin gene expression in various cell lineages, 5 kb of the 5V flanking region of the human secretin gene were investigated. As secretin is expressed in the brain and gut, a human duodenal adenocarcinoma cell (HuTu-80) and a human neuroblastoma cell (SH-SY5Y) were employed in the present study. In duodenal cells, an E-box and two GC-boxes were found to be essential for the human secretin promoter activity. In vivo (chromatin immunoprecipitation, ChIP) and in vitro binding studies (gel mobility shift) showed that these motifs were binding sites for transcription factors, namely, NeuroD, E2A, Sp1 and Sp3. Expression of various ratios of Sp1 and Sp3 in Drosophila SL2 cells and HuTu-80 cells reflected the importance of the stoichiometric ratio of Sp1 and Sp3 on the control of secretin gene expression. The GC-boxes are located within a putative CpG island suggesting a role of CpG methylation in human secretin gene regulation. Hyper-methylated promoter regions were observed in secretin non-expressing cells (PANC-1 and HepG2). Also, there was an augmentation of the secretin transcript levels when the cells were treated 5V-Aza-2V deoxycytidine (5V-Aza-dC). These evidences suggested that promoter methylation was a key regulator for the cell-specific expression of secretin. As a neuropeptide, secretin is expressed in distinct central neurons. However, there is no information regarding how secretin gene is regulated in neuronal cells. For this reason, a well established neuronal differentiation cell model, SH-SY5Y, was used. Not just that we found high secretin transcript and peptide levels in this cell, the secretin gene expression and its promoter activity were up-regulated upon all-trans retinoic acid (RA) treatment. Within the promoter, a functional GC-box was found to be regulated by a brain-specific Sp protein, Sp4, and ubiquitous factors Sp1 and Sp3. The RA-induced activation is a partial result of a decreased of Sp3. In addition to the GC-box, an N1 motif in the close proximity was also responsible for the RA-induced secretin gene activation. Competitive gel mobility shift and Southwestern blot studies revealed the binding of Nuclear Factor I (NFI) with the N1 motif. Consistent with this observation, NFI-C transcript levels are augmented after RA-treatment. We conclude that the RA-induction of secretin gene in neuronal cells is regulated by the combined actions of reducing Sp3 and increasing NFI-C expressions.
DescriptionPP. 133-188 of this journal issue entitled: 7th International Symposium on VIP, PACAP and Related Peptides
Persistent Identifierhttp://hdl.handle.net/10722/110318
ISSN
2015 Impact Factor: 1.813
2015 SCImago Journal Rankings: 0.915

 

DC FieldValueLanguage
dc.contributor.authorLee, TOen_HK
dc.contributor.authorTan-Un, KCen_HK
dc.contributor.authorChow, BKCen_HK
dc.date.accessioned2010-09-26T02:00:45Z-
dc.date.available2010-09-26T02:00:45Z-
dc.date.issued2005en_HK
dc.identifier.citationThe 7th International Symposium on VIP, PACAP and Related Peptides, Rouen, Normandy, France, 11-14 September 2005. In Regulatory Peptides, 2005, v. 130 n. 3, p. 167en_HK
dc.identifier.issn0167-0115en_HK
dc.identifier.urihttp://hdl.handle.net/10722/110318-
dc.descriptionPP. 133-188 of this journal issue entitled: 7th International Symposium on VIP, PACAP and Related Peptides-
dc.description.abstractSecretin is a member of the glucagon/secretin/vasoactive intestinal peptide (VIP) family. To unravel the mechanism that regulates the human secretin gene expression in various cell lineages, 5 kb of the 5V flanking region of the human secretin gene were investigated. As secretin is expressed in the brain and gut, a human duodenal adenocarcinoma cell (HuTu-80) and a human neuroblastoma cell (SH-SY5Y) were employed in the present study. In duodenal cells, an E-box and two GC-boxes were found to be essential for the human secretin promoter activity. In vivo (chromatin immunoprecipitation, ChIP) and in vitro binding studies (gel mobility shift) showed that these motifs were binding sites for transcription factors, namely, NeuroD, E2A, Sp1 and Sp3. Expression of various ratios of Sp1 and Sp3 in Drosophila SL2 cells and HuTu-80 cells reflected the importance of the stoichiometric ratio of Sp1 and Sp3 on the control of secretin gene expression. The GC-boxes are located within a putative CpG island suggesting a role of CpG methylation in human secretin gene regulation. Hyper-methylated promoter regions were observed in secretin non-expressing cells (PANC-1 and HepG2). Also, there was an augmentation of the secretin transcript levels when the cells were treated 5V-Aza-2V deoxycytidine (5V-Aza-dC). These evidences suggested that promoter methylation was a key regulator for the cell-specific expression of secretin. As a neuropeptide, secretin is expressed in distinct central neurons. However, there is no information regarding how secretin gene is regulated in neuronal cells. For this reason, a well established neuronal differentiation cell model, SH-SY5Y, was used. Not just that we found high secretin transcript and peptide levels in this cell, the secretin gene expression and its promoter activity were up-regulated upon all-trans retinoic acid (RA) treatment. Within the promoter, a functional GC-box was found to be regulated by a brain-specific Sp protein, Sp4, and ubiquitous factors Sp1 and Sp3. The RA-induced activation is a partial result of a decreased of Sp3. In addition to the GC-box, an N1 motif in the close proximity was also responsible for the RA-induced secretin gene activation. Competitive gel mobility shift and Southwestern blot studies revealed the binding of Nuclear Factor I (NFI) with the N1 motif. Consistent with this observation, NFI-C transcript levels are augmented after RA-treatment. We conclude that the RA-induction of secretin gene in neuronal cells is regulated by the combined actions of reducing Sp3 and increasing NFI-C expressions.-
dc.languageengen_HK
dc.publisherElsevier BV. The Journal's web site is located at http://www.elsevier.com/locate/regpepen_HK
dc.relation.ispartofRegulatory Peptidesen_HK
dc.rightsRegulatory Peptides. Copyright © Elsevier BV.en_HK
dc.titleTranscriptional regulation of the human secretin gene in duodenal and neuronal cellsen_HK
dc.typeConference_Paperen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0167-0115&volume=130&issue=3&spage=167&epage=&date=2006&atitle=Transcriptional+regulation+of+the+human+secretin+gene+in+duodenal+and+neuronal+cellsen_HK
dc.identifier.emailLee, TO: ltolee2@hkucc.hku.hken_HK
dc.identifier.emailTan-Un, KC: kctanun@hkucc.hku.hken_HK
dc.identifier.emailChow, BKC: bkcc@hkusua.hku.hken_HK
dc.identifier.authorityLee, TO=rp00727en_HK
dc.identifier.authorityTan-Un, KC=rp00787en_HK
dc.identifier.authorityChow, BKC=rp00681en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.regpep.2005.06.011-
dc.identifier.hkuros103153en_HK
dc.identifier.hkuros123547-
dc.identifier.hkuros157556-
dc.identifier.volume130en_HK
dc.identifier.issue3en_HK
dc.identifier.spage167en_HK

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