Regulation of the leukocyte integrin gene CD11c is mediated by AP1 and Ets transcription factors.
The leukocyte integrin gene, CD11c, encodes the chi subunit of the p150,95 (CD11c.CD18) receptor. Expression of the CD11c gene is predominately seen in monocytes, but has also been detected in some B- and T-cell neoplasms and in some large-cell lymphomas of uncertain origin. To elucidate the molecular mechanisms that govern the expression of CD11c, we have cloned and characterized the promoter region of this gene. The DNase I footprint and mobility shift analyses revealed five sites within the -86 to +40 region that interact with nuclear proteins. The -62 to -44 region contains two consensus sequences for AP1 (referred to as AP1-1 and AP1-2) and were shown to bind purified c-jun protein. Co-transfection of c-fos and c-jun expression constructs with a CD11c promoter-CAT fusion into HL60 cells led to a 6.7-fold increase in CD11c promoter activity. We show that c-fos and c-jun mediate their effects through both AP1-1 and AP1-2 which function in an additive manner. Regions -42 to -34 and -13 to -5 contain consensus sequences for Ets factors (referred to as Ets C and Ets A, respectively). Deletion of Ets resulted in a significant reduction in phorbol ester-induced expression of CD11c, whereas deletion of Ets A led to only a modest loss in CD11c expression. We show that Ets C cooperates with the AP1 sites to regulate CD11c expression.
Noti
J D
JD
Guthrie Research Institute, Sayre, PA 18840, USA.
Reinemann
C
C
Petrus
M N
MN
D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics / Q000378:metabolism; D018983:DNA Footprinting; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation; D016762:Genes, fos; D016758:Genes, jun; D006801:Humans; D016167:Integrin alphaXbeta2 / Q000235:genetics*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D017931:DNA Primers; D016167:Integrin alphaXbeta2; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase