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Structure of the human 5-HT7 receptor gene and characterization of its promoter region.
Gene. 2007 Apr 15; 391(1-2):252-63.GENE

Abstract

The molecular mechanism regulating serotonin 5-HT(7) receptor expression is still unclear. In this study we provide evidence that transcription of the 5-HT(7) gene is at least partly regulated by Sp1 and Sp3. We isolated and sequenced >3000 bp of the upstream sequences and identified by RACE a number of transcriptional initiation sites over a region of 300 bp upstream of the coding region. This region has a high GC content, but contains no obvious TATA or a CAAT box. Besides a Sp1/Sp3 consensus motif, regulatory elements for AP2, Egr-1 and MAZ are also present. Transient transfection assays using deletion variants indicated that the GC-rich region is essential for full promoter activity. The role of Sp1 in this was confirmed by transient overexpression of both wild type Sp1 or dominant-negative forms. By gel shift and supershift analyses, targeting the Sp1 consensus sequence and the GC-rich region just upstream of the transcription initiation sites, binding of Sp1 and Sp3 was demonstrated. Both in vitro as well as in vivo experiments, using a cell line which endogenously expresses the 5-HT(7) receptor, indicated that mithramycin A, an inhibitor of Sp1/3 transcription factor binding, was able to inhibit 5-HT(7) promoter activity. Taken together these results support the essential role of Sp factors in regulating 5-HT(7) promoter activity.

Authors+Show Affiliations

Laboratory of Eukaryotic Gene Expression and Signal Transduction (LEGEST), Department of Molecular Biology, Ghent University, UGent, K.L. Ledeganckstraat 35, B-9000 Gent, Belgium.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17321075

Citation

Laenen, Koen, et al. "Structure of the Human 5-HT7 Receptor Gene and Characterization of Its Promoter Region." Gene, vol. 391, no. 1-2, 2007, pp. 252-63.
Laenen K, Haegeman G, Vanhoenacker P. Structure of the human 5-HT7 receptor gene and characterization of its promoter region. Gene. 2007;391(1-2):252-63.
Laenen, K., Haegeman, G., & Vanhoenacker, P. (2007). Structure of the human 5-HT7 receptor gene and characterization of its promoter region. Gene, 391(1-2), 252-63.
Laenen K, Haegeman G, Vanhoenacker P. Structure of the Human 5-HT7 Receptor Gene and Characterization of Its Promoter Region. Gene. 2007 Apr 15;391(1-2):252-63. PubMed PMID: 17321075.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Structure of the human 5-HT7 receptor gene and characterization of its promoter region. AU - Laenen,Koen, AU - Haegeman,Guy, AU - Vanhoenacker,Peter, Y1 - 2007/01/26/ PY - 2007/01/05/received PY - 2007/01/08/revised PY - 2007/01/08/accepted PY - 2007/2/27/pubmed PY - 2007/5/30/medline PY - 2007/2/27/entrez SP - 252 EP - 63 JF - Gene JO - Gene VL - 391 IS - 1-2 N2 - The molecular mechanism regulating serotonin 5-HT(7) receptor expression is still unclear. In this study we provide evidence that transcription of the 5-HT(7) gene is at least partly regulated by Sp1 and Sp3. We isolated and sequenced >3000 bp of the upstream sequences and identified by RACE a number of transcriptional initiation sites over a region of 300 bp upstream of the coding region. This region has a high GC content, but contains no obvious TATA or a CAAT box. Besides a Sp1/Sp3 consensus motif, regulatory elements for AP2, Egr-1 and MAZ are also present. Transient transfection assays using deletion variants indicated that the GC-rich region is essential for full promoter activity. The role of Sp1 in this was confirmed by transient overexpression of both wild type Sp1 or dominant-negative forms. By gel shift and supershift analyses, targeting the Sp1 consensus sequence and the GC-rich region just upstream of the transcription initiation sites, binding of Sp1 and Sp3 was demonstrated. Both in vitro as well as in vivo experiments, using a cell line which endogenously expresses the 5-HT(7) receptor, indicated that mithramycin A, an inhibitor of Sp1/3 transcription factor binding, was able to inhibit 5-HT(7) promoter activity. Taken together these results support the essential role of Sp factors in regulating 5-HT(7) promoter activity. SN - 0378-1119 UR - https://www.unboundmedicine.com/medline/citation/17321075/Structure_of_the_human_5_HT7_receptor_gene_and_characterization_of_its_promoter_region_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0378-1119(07)00040-6 DB - PRIME DP - Unbound Medicine ER -