Identification of basic transcriptional elements required for rif gene transcription

The rif gene family is the largest multi-gene family in the malaria parasite Plasmodium falciparum. The gene products of rif genes, rifins, are clonally variant and transported to the surface of the infected erythrocyte where they are targets of the human immune response. Maximal rif transcription occurs during the late ring to early trophozoite stages of the intra-erythrocytic cycle. The factors involved in the transcriptional activation and repression of rif genes are not known. In this paper, we characterize several DNA elements involved in the regulation of rif transcription. We identify the upstream region that contains a functional promoter and the transcriptional start site of a rif gene. In addition, we identify two distinct regions within the rif upstream region involved in the transcriptional repression of these genes. These repressor sites are bound by nuclear protein factors expressed in different stages of the Plasmodium life cycle. We propose that the differential timing of binding provides a mechanism for the temporal repression of rif genes. In addition, we find that transcription profiles of upsA var genes and their neighbouring rif genes are unlinked.