CREB is involved in mouse annexin A1 regulation by cAMP and glucocorticoids

A cAMP and some glucocorticoid response elements have been underlined in the promoter of mouse annexin A1. To analyse the function of these DNA sequences, the role of cAMP and glucocorticoids, as well as the transcription factors involved in their activation, were investigated. A construct containing 1381 bp of the DNA 5'-flanking annexin A1 gene fused to LacZ was used. The level of activation of the reporter gene was analysed by transient transfection of the JEG3 cell line. Activation of beta-galactosidase expression was observed with both dibutyryl cAMP and dexamethasone when compared with cells treated with serum only. Simultaneous addition of dexamethasone and dibutyryl cAMP did not result in a synergistic effect but rather in a competitive one. Gel-shift assays with a probe including the cAMP response element-like element of the annexin A1 promoter revealed a main specific DNA-protein complex when cells were stimulated with dibutyryl cAMP and/or dexamethasone. In all cases CREB protein was identified by supershift analysis. We therefore conclude that this cAMP response element sequence plays a prominent role in the transactivation of the annexin A1 promoter by dibutyryl cAMP and that it is involved in the response to glucocorticoids.