The Sp1 transcription factor binds the CD11b promoter specifically in myeloid cells in vivo and is essential for myeloid-specific promoter activity

• Published in: The Journal of biological chemistry Vol. 268; no. 11; pp. 8230 - 8239
• Main Authors: Chen, H M, Pahl, H L, Scheibe, R J, Zhang, D E, Tenen, D G
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 15-04-1993
• Subjects: Amino Acid Sequence; Antigens, CD - genetics; Base Sequence; Binding Sites; Biological and medical sciences; Bone Marrow; CD11 Antigens; Cell Nucleus - metabolism; Cells, Cultured; DNA - blood; DNA - genetics; DNA - isolation & purification; Fundamental and applied biological sciences. Psychology; HeLa Cells; Humans; Introns; Lymphocytes - drug effects; Lymphocytes - immunology; Lymphocytes - metabolism; Methylation; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Monocytes - drug effects; Monocytes - immunology; Monocytes - metabolism; Mutagenesis, Insertional; Oligodeoxyribonucleotides; Promoter Regions, Genetic; Regulatory Sequences, Nucleic Acid; Restriction Mapping; Sp1 Transcription Factor - metabolism; Tetradecanoylphorbol Acetate - pharmacology; Transcription. Transcription factor. Splicing. Rna processing; Transfection; Tumor Cells, Cultured; Tissue specificity; Integrin; Transcription; Transcription factor; Transcription promoter; Myeloid cell
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)53086-6

The myeloid integrin CD11b is expressed selectively on the surface of mature macrophages, monocytes, neutrophils, and natural
killer cells. Lineage-specific expression is controlled at the level of mRNA transcription. Recent isolation of the CD11b
promoter shows that 92 base pairs (bp) of 5'-flanking DNA are sufficient to direct myeloid-specific expression of a reporter
gene. To characterize regulatory sequences important for promoter activity, we performed linker scanning analysis of the 92-bp
CD11b promoter and demonstrate that a sequence at bp -60 is essential for CD11b promoter activity. We show that this sequence
binds the transcription factor Sp1 in vitro and in vivo. In vivo the Sp1 site is bound only in myeloid (U937) cells, not in
cervical carcinoma (HeLa) cells. In addition, the macrophage transcription factor PU.1 binds the CD11b promoter in vitro and
in vivo close to the Sp1 site. We propose a model in which binding of a myeloid-specific factor (PU.1) allows a general factor
(Sp1) to bind in a tissue-specific fashion thereby contributing to the myeloid-specific expression of CD11b.