The LIM family transcription factor Isl-1 requires cAMP response element binding protein to promote somatostatin expression in pancreatic islet cells.
Many eukaryotic genes are regulated by cAMP through a conserved cAMP response element (CRE). Here we show that, in the pancreatic islet cell line Tu6, a well-characterized CRE in the somatostatin gene does not provide cAMP responsiveness but functions as an essential element for its basal activity. DNA-binding and functional analyses indicate that the cAMP-responsive factor CREB regulates somatostatin expression in these cells without requirement for phosphorylation at the protein kinase A-regulated Ser-133 phosphorylation site. In addition to the CRE site, cell-specific expression of the somatostatin gene requires a second promoter element, which binds the recently characterized LIM family protein Isl-1. Thus, Isl-1 and CREB appear to synergize on the somatostatin promoter to stimulate high-level expression in Tu6 cells. The ability of CREB to function in a phosphorylation-independent manner suggests a mechanism by which this protein can regulate gene transcription.
Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, CA 92037.
J
J
Leonard
P
P
Serup
G
G
Gonzalez
T
T
Edlund
M
M
Montminy
D001483:Base Sequence; D000242:Cyclic AMP / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D018398:Homeodomain Proteins; D066298:In Vitro Techniques; D007515:Islets of Langerhans / Q000502:physiology*; D060850:LIM-Homeodomain Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D013004:Somatostatin / Q000235:genetics*; D014157:Transcription Factors / Q000502:physiology*; D014407:Tumor Cells, Cultured
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D060850:LIM-Homeodomain Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1; D013004:Somatostatin; D000242:Cyclic AMP