Using computer methods for detecting conserved amino acid sequence motifs, we show that the chromatin organization modifier (chrome) domain that has been previously identified in several proteins involved in transcription down-regulation is present in a much larger group of (putative) chromatin-binding proteins, some of which are positive rather than negative regulators of transcription, The most interesting new members of the chrome superfamily are Drosophila male-specific lethal (MSL-3) protein involved in the X chromosome gene dosage compensation in the males and human retinoblastoma-binding protein RBP-1. We show that the chrome domain is duplicated in several chromatin-binding proteins and use this observation to interpret recent results on chromatin binding obtained with chimeric chrome domain- containing proteins, We hypothesize that the chrome domain may be a vehicle that delivers both positive and negative transcription regulators to the sites of their action on chromatin.