The zinc finger transcription factor ZBP-89 is a repressor of the human beta 2-integrin CD11b gene.
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 exist regarding potential down-regulatory factors, especially in the later stages of differentiation. Using 2 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 cells were induced to differentiate into monocytelike 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.
Park
Heiyoung
H
Leukocyte Biology and Inflammation Program, Renal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Shelley
C Simon
CS
Arnaout
M Amin
MA
D001483:Base Sequence; D039481:CD11b Antigen / Q000235:genetics*; D002454:Cell Differentiation; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000166:cytology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D020298:U937 Cells
D039481:CD11b Antigen; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C110951:ZNF148 protein, human