GABP AND PU.1 COMPETE FOR BINDING, YET COOPERATE TO INCREASE CD18 (BETA(2) LEUKOCYTE INTEGRIN) TRANSCRIPTION

CD18 (beta(2) leukocyte integrin) is a leukocyte specific adhesion mol ecule that plays a crucial role in immune and inflammatory responses, A 79-nucleotide fragment of the CD18 promoter is sufficient to direct myeloid transcription, The CD18 promoter is bound by the B lymphocyte- and myeloid-restricted ets factor, PU.1, and disruption of the PU.1-b inding sites significantly reduces promoter activity, However, PU.1 al one cannot fully account for the leukocyte-specific and myeloid-induci ble transcription of CD18, We identified a ubiquitously expressed nucl ear protein complex of extremely low electrophoretic mobility that als o binds to this region of the CD18 promoter, This binding complex is a heterotetramer composed of GABP alpha, an ets factor, and GABP beta, a subunit with homology to Drosophila Notch, GABP alpha competes with the lineage restricted factor, PU.1, for the same critical CD18 ets si tes, The CD18 promoter is activated in myeloid cells by transfection w ith both GABP alpha and GABP beta together, but not by either factor a lone, Transfection of non-hematopoietic cells with the two GABP subuni ts together with PU.1 is sufficient to activate CD18 transcription in otherwise non-permissive cells, Thus, GABP and PU.1 compete for the sa me binding sites but cooperate to activate CD18 transcription.