TAILIEUCHUNG - Báo cáo khoa học: Characterization of promoter 3 of the human thromboxane A2 receptor gene A functional AP-1 and octamer motif are required for basal promoter activity

The TPaand TPbisoforms of the human thromboxane A2 receptor (TP) arise by differential splicing but are under the transcriptional control of two distinct promoters, termed Prm1 and Prm3, respectively (Coyle et al. 2002Eur J Biochem269, 4058–4073). The aim of the current study was to determine the key factors regulating TPbexpression by functionally charac-terizing Prm3, identifying the core promoter and the cis-acting elements regulating basal Prm3 activity. | iFEBS Journal Characterization of promoter 3 of the human thromboxane A2 receptor gene A functional AP-1 and octamer motif are required for basal promoter activity Adrian T. Coyle and B. Therese Kinsella Department of Biochemistry Conway Institute of Biomolecular and BiomedicalResearch University College Dublin Belfield Dublin Ireland Keywords AP-1 gene expression isoforms Oct promoter splicing thromboxane receptor Correspondence B. T. Kinsella Department of Biochemistry Conway Institute of Biomolecular and BiomedicalResearch University College Dublin Belfield Dublin 4 Ireland Fax 353 1 2837211 Tel 353 1 7166727 E-mail Received 18 October 2004 revised 8 December 2004 accepted 20 December 2004 doi The TPa and TPb isoforms of the human thromboxane A2 receptor TP arise by differential splicing but are under the transcriptional control of two distinct promoters termed Prm1 and Prm3 respectively Coyle et al. 2002 Eur J Biochem 269 4058-4073 . The aim of the current study was to determine the key factors regulating TPb expression by functionally characterizing Prm3 identifying the core promoter and the cis-acting elements regulating basal Prm3 activity. Hence the ability of Prm3 and a series of Prm3 deleted mutated subfragments to direct reporter gene expression in human erythroleukemia and human embryonic kidney 293 cells was investigated. It was established that nucleotides -118 to 1 are critical for core Prm3 activity in both cell types. Furthermore three distinct regulatory regions comprising of an upstream repressor sequence located between -404 to -320 and two positive regulatory regions required for efficient basal gene expression located between -154 to -106 and -50 to 1 were identified within the core Prm3. Deletion and site-directed mutagenesis of consensus Oct-1 2 and AP-1 elements within the latter -154 to -106 and -50 to 1 regions respectively substantially reduced Prm3 activity while mutation .

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