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Involvement of Cyclic AMP Response Element (CRE) in Exendin‐4 Induction of Rat Egr‐1 Gene
Author(s) -
Kang JungHoon,
Kim MyungJun,
Jang HwaIn,
Rhie DuckJoo,
Yoon Shin Hee,
Hahn Sang June,
Kim MyungSuk,
Jo YangHyeok
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.lb68-c
Subject(s) - microbiology and biotechnology , promoter , serum response element , response element , gene , biology , gene expression , ex vivo , transcription factor , chemistry , genetics , serum response factor , in vitro
We recently observed that exendin‐4 (EX‐4), a potent agonist of GLP‐1, induced cyclin D1 expression through the activation of putative cAMP‐responsive element (CRE) site and Egr‐1 binding site on cyclin D1 promoter (J Endocrinol, 2006; Diabetologia, 2006, both in press). In the present study, induction of Egr‐1 expression by EX‐4 and the cis‐acting elements involved in the transcriptional activation of Egr‐1 gene were investigated in INS‐cells. EX‐4 (10 nM) rapidly and transiently induced the expressions of Egr‐1 mRNA and protein. These inductions were completely inhibited by a specific PKA inhibitor, H‐89, suggesting the involvement of cAMP/PKA signaling pathway. In promoter assay using serial‐deletion constructs of rat Egr‐1 promoter, EX‐4 induced the highest promoter activity with full‐length constructs (−462 to +27) and the activity of similar degree with the construct deleted up to −124. The construct deleted to −73, which was without serum response elements (SREs) site known to be involved in regulating Egr‐1 transcription, still responded to EX‐4 moderately. However, further deletion to −46 failed to respond to EX −4. Thus, in examining the role of the nucleotide region from −73 to −46, mutation of the putative CRE site located at −69 resulted in 52% reduction in promoter activity in response to EX‐4. This study indicates that the putative CRE site as well as the SRE site is required for the induction of Egr‐1 gene by EX‐4. This research was grant‐supported by Korea Science and Engineering Foundation (R‐2004‐000‐10127‐0), Republic of Korea.