Role of the Sp Family of Transcription Factors on Glucagon Receptor Gene Expression

A critical role of Sp1 transcription factor in regulating gene expression in response to insulin and other hormones

“…As was the case for insulin-mediated regulation of gene expression via Sp1 or Sp3, different members of Sp family appear to preferentially activate various target genes associated with other hormone systems. For instance, the distal promoter of the murine glucagon receptor gene contains five GC elements all of which could bind to Sp1 and Sp3 in vitro; however, only one of these GC elements, with a higher binding affinity for Sp3 than Sp1, was needed to optimally activate the glucagon receptor in the pancreatic β cell line MIN6 (Geiger et al, 2001). A complex role for the Sp family of transcription factors in controlling the fetal-to-postnatal switch in the expression of growth hormone receptor (GHR) gene was similarly demonstrated by Yu et al (1999) who showed that Sp3 was more potent than Sp1 in transactivating the GHR promoter in Drosophila SL-2cells (lacking Sp proteins).…”

Glucagon receptors

“…Furthermore, a single promoter region, located upstream from the most distal untranslated exon, has been defined in the rat GR gene [41], whereas both a proximal and a distal promoter, located upstream from the first coding exon and from the single untranslated exon, respectively, have been described in the mouse [45] and human [44] genes. Structurally, these promoters lack consensus TATA and CAAT boxes, are GC rich and contain several putative Sp1 binding sites, as many promoters of housekeeping genes [46]. Other interesting features include, in the rat promoter (between -545 and -527), a glucose response element consisting of a highly palindromic sequence of 19 nucleotides, centered on two E boxes (CACGTG and CAGCTG) separated by three nucleotides [41]; and in the proximal human promoter (between -1062 and -354), several CRE, C/EBPa and AP-1 elements, known to be involved in cAMP regulation of gene expression [44].…”

Identification of a novel human glucagon receptor promoter: Regulation by cAMP and PGC-1α

“…Both the mouse and the rat glucagon receptor promoters have been well characterized (Burcelin et al, 1995;Geiger et al, 2000Geiger et al, , 2001aPortois et al, 1999) and the glucose response of the rat promoter has also been extensively studied (Portois et al, , 2000(Portois et al, , 2002Svoboda et al, 1999) whereas the mechanism by which cAMP downregulates glucagon receptor expression has not been defined. The structure of the rat and mouse glucagon receptor genes has been found to be very similar, except that the rat gene only has one functional promoter, whereas the mouse gene has two active promoters separated by a large 3.8 kb intron (Burcelin et al, 1995;Geiger et al, 2000;Portois et al, 1999).…”