The proto-oncogene PU.1 regulates expression of the myeloid-specific CD11b promoter.
The myeloid integrin CD11b is expressed selectively on the surface of mature monocytes, macrophages, granulocytes, and natural killer cells. Tissue-specific and developmentally regulated expression of CD11b is controlled at the level of mRNA transcription, and recent characterization of the human CD11b promoter indicates that the first 92 bp of 5'-flanking DNA are sufficient to direct tissue-specific expression of a reporter gene. Here we show that the sequence AAAAGGAGAAG at base pair -20 of the CD11b promoter binds the proto-oncogene PU.1 in vitro and that mutation of this site significantly reduces the ability of the CD11b promoter to direct expression of a reporter gene in myeloid cells but not in nonmyeloid cells. PU.1 may thus represent a major determinant of the myeloid expression of CD11b.
Pahl
H L
HL
Department of Medicine, Beth Israel Hospital, Boston, Massachusetts 02215.
Scheibe
R J
RJ
Zhang
D E
DE
Chen
H M
HM
Galson
D L
DL
Maki
R A
RA
Tenen
D G
DG
D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D018845:CD11 Antigens; D002460:Cell Line; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology / Q000378:metabolism*; D009841:Oligonucleotides; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000378:metabolism; D015682:Retroviridae Proteins, Oncogenic
D015703:Antigens, CD; D018845:CD11 Antigens; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D009841:Oligonucleotides; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D015682:Retroviridae Proteins, Oncogenic; C062022:v-Spi-1 protein, Friend spleen focus-forming virus; D004247:DNA