The Zinc Finger Transcription Factor Transforming Growth Factor β-Inducible Early Gene-1 Confers Myeloid-specific Activation of the Leukocyte Integrin CD11d Promoter

CD11d encodes the αD subunit for a leukocyte integrin that is expressed on myeloid cells. In this study we show that the –100 to –20 region of the CD11d promoter confers myeloid-specific activation of the CD11d promoter. Transforming growth factor β-inducible early gene-1 (TIEG1) was isolated in a yeast one-hybrid screen using the –100 to –20 region of the CD11d promoter as bait. Purified GST·TIEG1 protein was able to bind within the –61 to –45 region that overlaps a shorter binding site for Sp1. Transient overexpression of TIEG1 activated the CD11d promoter specifically in myeloid cells, whereas, down-regulation of TIEG1 with small interfering TIEG1 RNA also down-regulated expression of CD11d. In vivo, TIEG1 does not physically interact with Sp1. Cotransfection and electrophoretic mobility shift analyses of TIEG1, Sp1, and Sp3 revealed that TIEG1 competes with these Sp proteins for binding to overlapping sites in the CD11d promoter. Although TIEG1 and Sp1 are ubiquitously expressed in myeloid and non-myeloid cells, chromatin immunoprecipitation assays revealed differential occupancy of the CD11d promoter by these factors. In undifferentiated myeloid and non-myeloid cells, occupancy of the CD11d promoter by TIEG1 is similar. Upon differentiation of myeloid cells and subsequent up-regulation of CD11d expression, TIEG1 occupancy increases. In contrast, occupancy by TIEG1 remains low in non-myeloid cells exposed to phorbol ester. We propose that up-regulation of CD11d expression following differentiation of myeloid cells is mediated through increased binding of TIEG1 binding to the CD11d promoter.