Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2007-3-9
pubmed:abstractText
The insulin promoter contains a number of dissimilar cis-acting regulatory elements that bind a range of tissue specific and ubiquitous transcription factors. Of the regulatory elements within the insulin promoter, the cyclic AMP responsive element (CRE) binds by far the most diverse array of transcription factors. Rodent insulin promoters have a single CRE site, whereas there are four CREs within the human insulin gene, of which CRE2 is the only one conserved between species. The aim of this study was to characterise the human CRE2 site and to investigate the effects of the two principal CRE-associated transcription factors; CREB-1 and ATF-2. Co-transfection of INS-1 pancreatic beta-cells with promoter constructs containing the human insulin gene promoter placed upstream of the firefly luciferase reporter gene and expression plasmids for ATF-2 or CREB-1 showed that ATF-2 stimulated transcriptional activity while CREB-1 elicited an inhibitory effect. Mutagenesis of CRE2 diminished the effect of ATF-2 but not that of CREB-1. ATF-2 was shown to bind to the CRE2 site by electrophoretic mobility shift assay and by chromatin immunoprecipitation, while siRNA mediated knockdown of ATF-2 diminished the stimulatory effects of cAMP related signalling on promoter activity. These results suggest that ATF-2 may be a key regulator of the human insulin promoter possibly stimulating activity in response to extracellular signals.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:volume
1769
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
79-91
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
ATF-2 stimulates the human insulin promoter through the conserved CRE2 sequence.
pubmed:affiliation
School of Medical Sciences, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB25 2ZD, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't