During U937 monocytic differentiation repression of the CD43 gene promoter is mediated by the single-stranded DNA binding protein Pur alpha.
Human CD43 is an abundant, heavily glycosylated molecule expressed exclusively on the surface of leucocytes. When leucocytes are at rest, CD43 acts to prevent intercellular interaction but during leucocyte differentiation such cell-cell interaction is facilitated by CD43. This change in the function of CD43 is mediated in part by a reduction in its level of expression. Previous studies have implicated proteolytic cleavage events at the cell surface in causing such reduction. Here, we report that, in an in vitro model of leucocyte differentiation, CD43 mRNA levels were also subject to reduction. Specifically, we demonstrated that within 48 h of the cell line U937 being induced to differentiate along the monocytic pathway, CD43 mRNA levels were reduced by 69%. This decline coincided with a decrease in the activity of the CD43 gene promoter mediated by the single-stranded DNA binding protein Pur alpha. Previously, we have demonstrated that Pur alpha mediates induction of the CD11c beta 2 integrin promoter during U937 differentiation. Consequently, Pur alpha represents a potential means by which the induction of pro-adhesive molecules and the repression of anti-adhesive molecules is co-ordinated during leucocyte differentiation.
Shelley
C S
CS
Renal Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA. shelley@receptor.mgh.harvard.edu
Da Silva
N
N
Teodoridis
J M
JM
D015703:Antigens, CD; D002448:Cell Adhesion / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004268:DNA-Binding Proteins; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D051917:Leukosialin; D011401:Promoter Regions, Genetic; D017433:Protein Structure, Secondary; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000235:genetics*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors; D020298:U937 Cells
D015703:Antigens, CD; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D051917:Leukosialin; C501130:PURA protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; C465014:SPN protein, human; D012795:Sialoglycoproteins; D014157:Transcription Factors; D013755:Tetradecanoylphorbol Acetate