Lysozyme protects us from the ever-present danger of bacterial infection. The expression of lysozyme is, in part, regulated by the Ets factor, mycloid elf-1-like factor (MEF). MEF binds to the ETS site of the lysozyme promoter at -46 to -40 bp. Closer analysis of the promoter using a series of deletion mutants and point mutants indicated that the region around -75 bp is also essential in regulating the activity of lysozyme. The sequences in this region correspond to the Sp1 consensus binding site. Sp1 is known to regulate a variety of house-keeping and tissue-specific genes by itself or with other transcription factors like AP-1 or ETS. We indicate here that Sp1 regulates the lysozyme gene by binding to the GT-core sequences of lysozyme promoter. Treatment with mithramycin A down-regulated the promoter activity and the transfection of anti-sense Sp1 induced a decrease in the endogenous expression of lysozyme. (C) 2004 Elsevier Inc. All rights reserved.