C/EBP, NF-kappa B, and c-Ets family members and transcriptional regulation of the cell-specific and inducible macrophage inflammatory protein 1 alpha immediate-early gene.
Macrophage inflammatory protein 1 alpha (MIP-1 alpha) cytokine gene expression is restricted to a limited number of cells of hemopoietic origin and is rapidly and transiently induced by serum and endotoxin in macrophages. A single nuclear DNase I-hypersensitive site, which maps to the proximal promoter of the MIP-1 alpha gene, was identified in macrophage cells but was absent in cells which do not express basal levels of MIP-1 alpha mRNA. The proximal promoter sequences (+36 to -220 bp) are sufficient to confer cell-specific and inducible transcription in transfection assays. In vitro DNA-binding studies revealed five major nuclear protein binding sites in the proximal promoter which bind C/EBP, NF-kappa B, and/or c-Ets family members. Cell-specific differences in DNA binding by members of the NF-kappa B and c-Ets families correlate with the cell-specificity of MIP-1 alpha gene expression and the chromosomal conformation of the promoter. Changes in promoter binding by members of the C/EBP and NF-kappa B families correlate with the transcriptional up-regulation observed in serum- or endotoxin-stimulated macrophages in functional studies.
Grove
M
M
CRC Beatson Laboratories, Beatson Institute for Cancer Research, Garscube Estate, Bearsden, Glasgow, United Kingdom.
Plumb
M
M
D000818:Animals; D001483:Base Sequence; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002843:Chromatin / Q000648:ultrastructure; D016207:Cytokines / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D003850:Deoxyribonuclease I / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D008969:Molecular Sequence Data; D015846:Monokines / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000235:genetics; D016415:Sequence Alignment; D014157:Transcription Factors; D014158:Transcription, Genetic
D022762:CCAAT-Enhancer-Binding Proteins; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D002843:Chromatin; D016207:Cytokines; D004268:DNA-Binding Proteins; D006133:Growth Substances; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D016328:NF-kappa B; D009687:Nuclear Proteins; D009838:Oligodeoxyribonucleotides; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D014157:Transcription Factors; D003850:Deoxyribonuclease I