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 ma turation. Recently, an additional regulatory feature was discovered: the ge ne 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 de rived from adult animals. This finding provided a molecular tool to investi gate the heretofore ill-defined differences between embryonic/fetal- and ad ult-type macrophages, We showed that the low expression in the embryo is as sociated with reduced activity of the myeloid-specific -2.7 kb lysozyme enh ancer. Our protein-binding analyses and transfection studies demonstrated t hat this enhancer, in order to be fully active in activated macrophages, re quires the combined action of C/EBPs, PU.1, and a third, as yet unidentifie d, protein binding to an AP-1-like site. Of these three, PU.1 and C/EBPs di splay significantly reduced nuclear DNA-binding activities in embryo-derive d macrophages compared with adult-type cells. These results point to differ ent roles of C/EBPs and PU.1 in embryonic/fetal and adult myelopoiesis.