Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

Genomic organization and regulation of the human orexin (hypocretin) receptor 2 gene : identification of alternative promoters

Tools
- Tools
+ Tools

Chen, Jing and Randeva, Harpal S. (2010) Genomic organization and regulation of the human orexin (hypocretin) receptor 2 gene : identification of alternative promoters. Biochemical Journal, Vol.427 (No.Part 3). pp. 377-390. doi:10.1042/BJ20091755

Research output not available from this repository, contact author.
Official URL: http://dx.doi.org/10.1042/BJ20091755

Request Changes to record.

Abstract

Orexins (hypocretins), acting via their receptors, are involved in the control of feeding behaviour, sleep, arousal and energy homoeostasis. However, regulation of the human orexin receptor 2 (hOX2R) gene remains unknown. We have identified four transcripts arising from alternative splicing from three exons. These exon 1 variants were designated exons 1A, 1B and 1C on the basis of their 5'-3' order. RT (reverse transcription) PCR demonstrates the differential expression in various human tissues. The alternative 5'-UTRs (untranslated regions) possessed by these isoforrns have different translational efficiencies, which regulate the level of protein expression. In the present study, we have demonstrated that the hOX2R gene is regulated by two promoters and the novel transcripts are regulated by the distal promoter located upstream of exon 1A. We have demonstrated that the AP-1 (activator protein 1) motif is critical for sustaining the basal activity of distal promoter. Analysis of the proximal promoter revealed the region regulating promoter activity contained putative binding elements including those for CREB (cAMP-response-element-binding protein), GATA-2 and Oct-1. Using the chromatin immunoprecipitation assay, we demonstrated that CREB, GATA-2 and Oct-1 transcription factors bind to these critical regulatory promoter elements. Mutational studies suggested that these motifs functioned independently, but have a compound effect regulating hOX2R gene transcription. Furthermore, proximal promoter activity is enhanced by both PKA (protein kinase A) and PKC (protein kinase C) pathway activation, via binding of CREB and GATA-2 transcription factors. In conclusion, we have demonstrated that expression of hOX2R is regulated by a complex involving a proximal PKA/PKC-regulated promoter and a distal promoter regulating tissue-specific expression of alternative transcripts which in turn post-transcriptionally regulate receptor levels.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016)
Faculty of Medicine > Warwick Medical School
Journal or Publication Title: Biochemical Journal
Publisher: Portland Press
ISSN: 0264-6021
Official Date: 1 May 2010
Dates:
DateEvent
1 May 2010Published
Volume: Vol.427
Number: No.Part 3
Number of Pages: 14
Page Range: pp. 377-390
DOI: 10.1042/BJ20091755
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: General Charities of the City of Coventry, British Heart Foundation
Grant number: PG/03/131/15192

Data sourced from Thomson Reuters' Web of Knowledge

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item
twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us