RFX1, a single DNA-binding protein with a split dimerization domain, generates alternative complexes.

The transcription of various viral and cellular genes is regulated by palindromic and nonpalindromic DNA sites resembling the EP element of the hepatitis B virus enhancer, which generate similar DNA-protein complexes. The upper EP complex contains homodimers of the transcription regulator RFX1. We show that RFX1 possesses a split, extended dimerization domain composed of several evolutionarily conserved boxes, one of which was previously shown to mediate dimerization. Such an unusually long and complex dimerization domain could potentially serve for generating multiple complexes. In addition to the previously characterized complex, RFX1 generated a novel DNA-protein complex of extremely low mobility, formed only with palindromic DNA sites. Different deletions within the dimerization domain altered the relative abundance of the two complexes, suggesting an interplay between them. Formation of the low mobility complex correlated with transcriptional repression, in that both activities were mediated by several portions of the conserved region. Our results propose a mechanism by which the extended dimerization domain mediates the formation of alternative homodimeric complexes, which differ in the nature of the intersubunit interaction. By participating in different types of interactions, this domain may regulate the relative abundance of the different complexes, thus affecting transcriptional activity.