Fig. P1.

A model for var gene regulation through promoter–promoter interaction, which is mediated by insulator-like DNA elements. (A) In a properly regulated var gene, the PEs (red circles) bind to specific nuclear proteins that mediate the interaction between the var and the intron promoters, thus enabling the intron promoter to silence the var promoter. Any alteration in the specific paired structure of these elements by either deletion (B) or insertion (C) of additional elements results in an unregulated var gene, which cannot be silenced and is not “counted” as a var gene for mutually exclusive expression.