Linked Life Data

20156195

Source:http://linkedlifedata.com/resource/pubmed/id/20156195

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-4-14
pubmed:databankReference
pubmed:abstractText
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 isoforms 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1470-8728
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
427
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
377-90
pubmed:dateRevised
2010-6-29
pubmed:meshHeading
pubmed-meshheading:20156195-5' Untranslated Regions, pubmed-meshheading:20156195-Alternative Splicing, pubmed-meshheading:20156195-Amino Acid Motifs, pubmed-meshheading:20156195-Base Sequence, pubmed-meshheading:20156195-Cell Line, pubmed-meshheading:20156195-Chromatin Immunoprecipitation, pubmed-meshheading:20156195-Chromosome Walking, pubmed-meshheading:20156195-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:20156195-Exons, pubmed-meshheading:20156195-GATA2 Transcription Factor, pubmed-meshheading:20156195-Humans, pubmed-meshheading:20156195-Introns, pubmed-meshheading:20156195-Molecular Sequence Data, pubmed-meshheading:20156195-Mutagenesis, Site-Directed, pubmed-meshheading:20156195-Octamer Transcription Factor-1, pubmed-meshheading:20156195-Polymerase Chain Reaction, pubmed-meshheading:20156195-Promoter Regions, Genetic, pubmed-meshheading:20156195-Protein Isoforms, pubmed-meshheading:20156195-Receptors, G-Protein-Coupled, pubmed-meshheading:20156195-Receptors, Neuropeptide, pubmed-meshheading:20156195-Transcription Initiation Site
pubmed:year
2010
pubmed:articleTitle
Genomic organization and regulation of the human orexin (hypocretin) receptor 2 gene: identification of alternative promoters.
pubmed:affiliation
Clinical Sciences Research Institute, University of Warwick, Coventry, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't