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Negative cooperativity between juxtaposed E‐box and cAMP/TPA responsive elements in the cholecystokinin gene promoter
Author(s) -
Rourke Ian J,
Hansen Thomas vO,
Nerlov Claus,
Rehfeld Jens F,
Nielsen Finn C
Publication year - 1999
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(99)00320-8
Subject(s) - cholecystokinin , cooperativity , chemistry , gene , biophysics , microbiology and biotechnology , promoter , biology , biochemistry , gene expression , receptor
The promoter of the cholecystokinin (CCK) gene possesses evolutionary conserved juxtaposed E‐box and cAMP/TPA responsive elements (CRE/TRE). We have examined the functional interaction of these two sites. As previously noted, c‐Jun/c‐Fos heterodimers greatly increase promoter activity through association with the CRE/TRE. Mutation of the E‐box enhanced the activation by c‐Jun/c‐Fos, as well as stimulation by forskolin and bFGF, that acts through the CRE/TRE site. Moreover, c‐Jun/c‐Fos stimulation was inhibited by co‐expression of c‐Myc and Max. The results indicate that factors associating with the E‐box exhibit a negative cooperative effect on the activation via the CRE/TRE element. We propose that this mechanism plays a significant role in CCK gene transcription and other genes with juxtaposed E‐box and CRE/TRE.