One of the chicken lysozyme gene silencers binds two transcription factors, v-ERBA or the thyroid hormone receptor and NeP1 (negative protein 1), a new silencer binding protein. NeP1 is neutral on a monomeric binding site, but mediates weak repression on a multimerized site and strong synergistic repression in conjunction with v-ERBA on the wild-type silencer. Depending on the presence or absence of ligand, synergistic induction or repression is seen with the thyroid hormone receptor. This synergism is not based on cooperative DNA-binding as measured in vitro. The NeP1 DNA-binding activity is dependent on zinc ions, the binding site is characterized by a footprint of approximately 50 bp. NeP1 has a molecular weight of 140 to 160 kDa and has been enriched by affinity columns.