CD18 (BETA(2) LEUKOCYTE INTEGRIN) PROMOTER REQUIRES PU.1 TRANSCRIPTION FACTOR FOR MYELOID ACTIVITY

Normal cellular differentiation is Linked to tightly regulated gene tr anscription. However, the DNA elements and trans-acting factors that r egulate transcription in myeloid cells are poorly defined. CD18, the b eta chain of the leukocyte integrins, is transcriptionally regulated d uring myeloid differentiation. The CD18 promoter is active after trans fection into myeloid cells. We demonstrate that a region of the CD18 p romoter that contains two binding sites for the PU.1 transcription fac tor is required for activity in myeloid cells. These sites are bound b y in vitro translated PU.1 and by PU.1 from myeloid nuclear extracts. Mutagenesis of these sites abrogates binding by PU.1 and substantially decreases promoter activity in myeloid cells. Thus, the leukocyte-spe cific transcription factor PU.1 is required for myeloid activity of CD 18.