Overlapping CRE and E-box promoter elements can independently regulate COX-2 gene transcription in macrophages

Macrophage cyclooxygenase-2 (COX-2) transcription is mediated through the c ollaboration of different promoter elements. Here, the role of an overlappi ng cyclic AMP responsive element (CRE)/E-box was investigated. Nuclear prot eins bound both the CRE and E-box, which synergized with other promoter ele ments to induce COX-2 transcription. Endotoxin induced binding of nuclear p roteins to the CRE and E-box and each element independently induced higher COX-2 transcription levels than the overlapping CRE/E-box. Transcription fa ctors associated with the CRE binding complex included c-Jun and CRE bindin g protein and with the E-box binding complex USF-1; their overexpression si gnificantly induced COX-2 transcription. Therefore, both CRE and E-box prom oter elements regulate COX-2 transcription in macrophages. (C) 2001 Publish ed by Elsevier Science B.V. on behalf of the Federation of European Biochem ical Societies.