Differential activity of the -2.7 kb chicken lysozyme enhancer in macrophages of different ontogenic origins is regulated by C/EBP and PU.1 transcription factors.
Expression of the chicken lysozyme gene is upregulated during macrophage maturation. Recently, an additional regulatory feature was discovered: the gene is differentially expressed in macrophages of embryonic/fetal and adult origin. The lysozyme gene is only weakly expressed in mature embryo-derived macrophages, whereas there is a high level of expression in macrophages derived from adult animals. This finding provided a molecular tool to investigate the heretofore ill-defined differences between embryonic/fetal- and adult-type macrophages. We showed that the low expression in the embryo is associated with reduced activity of the myeloid-specific -2.7 kb lysozyme enhancer. Our protein-binding analyses and transfection studies demonstrated that this enhancer, in order to be fully active in activated macrophages, requires the combined action of C/EBPs, PU.1, and a third, as yet unidentified, protein binding to an AP-1-like site. Of these three, PU.1 and C/EBPs display significantly reduced nuclear DNA-binding activities in embryo-derived macrophages compared with adult-type cells. These results point to different roles of C/EBPs and PU.1 in embryonic/fetal and adult myelopoiesis.
Faust
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N
Institute for Biology III, University of Freiburg, Germany.
Bonifer
C
C
Sippel
A E
AE
D000375:Aging; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins; D002460:Cell Line; D002642:Chick Embryo; D002645:Chickens; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D009113:Muramidase / Q000235:genetics*; D009154:Mutation; D009687:Nuclear Proteins / Q000378:metabolism*; D020033:Protein Isoforms / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D014162:Transfection; D000099232:Proto-Oncogene Protein Spi-1
D022762:CCAAT-Enhancer-Binding Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D009113:Muramidase; D009687:Nuclear Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1