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Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-03-0680. This Article Full Text (PDF) All Versions of this Article: 2002-03-0680v1 101/3/894    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Park, H. Articles by Arnaout, M A. Search for Related Content PubMed PubMed Citation Articles by Park, H. Articles by Arnaout, M A. Social Bookmarking                   What's this? Submitted March 4, 2002 Accepted September 11, 2002 The zinc finger transcription factor ZBP-89 is a repressor of the human ß2 integrin CD11b gene Heiyoung Park, C Simon Shelley, and M Amin Arnaout* Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA * Corresponding author; email: arnaout{at}receptor.mgh.harvard.edu. Integrin CD11b is a differentiation marker of the myelomonocytic lineage and an important mediator of inflammation. Expression of the CD11b gene is transcriptionally induced as myeloid precursors differentiate into mature cells, then drops as monocytes further differentiate into macrophages. Previous studies have identified elements and factors involved in the transcriptional activation of the CD11b gene during myeloid differentiation, but no data exists regarding potential down-regulatory factors, especially in the later stages of differentiation. Using two copies of a GC-rich element (-141 to -110) in the CD11b promoter, we probed a cDNA expression library for interacting proteins. Three clones were identified among 9.1 million screened, all encoding the DNA binding domain of the zinc finger factor ZBP-89. Overexpression of ZBP-89 in the monocyte precursor cell line U937 reduced CD11b promoter-driven luciferase activity when U937 were induced to differentiate into monocyte-like cells using phorbol esters. To identify the differentiation stage at which ZBP-89 repression of the CD11b gene is exerted, the protein level of ZBP-89 was correlated with that of CD11b mRNA in differentiating U937 as well as in normal human monocytes undergoing in vitro differentiation into macrophages. A clear inverse relationship was observed in the latter but not the former state, suggesting that ZBP-89 represses CD11b gene expression during the further differentiation of monocytes into macrophages. 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