Infections with protozoa parasites are associated with high burdens of morbidity and mortality across the developing world. Despite extensive efforts to control the transmission of these parasites, the spread of populations resistant to drugs and the lack of effective vaccines against them contribute to their persistence as major public health problems. Parasites should perform a strict control on the expression of genes involved in their pathogenicity, differentiation, immune evasion, or drug resistance, and the comprehension of the mechanisms implicated in that control could help to develop novel therapeutic strategies. However, until now these mechanisms are poorly understood in protozoa. Recent investigations into gene expression in protozoa parasites suggest that they possess many of the canonical machineries employed by higher eukaryotes for the control of gene expression at transcriptional, posttranscriptional, and epigenetic levels, but they also contain exclusive mechanisms. Here, we review the current understanding about the regulation of gene expression in Plasmodium sp., Trypanosomatids, Entamoeba histolytica and Trichomonas vaginalis.

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EhPgp1 is one of the multidrug resistance genes expressed in drug resistant trophozoites from Entamoeba histolytica. Previous studies in our laboratory have demonstrated that two C/EBP sites participate in the transcriptional activation of this gene. However there is other relevant region that also governs the regulation of EhPgp1 expression in clone C2. In this report we provide evidence that transcription of the EhPgp1 gene is at least partly regulated by the cis-acting R9 repeated sequences and EhEBP1 protein. Structural analysis of the region from -234 to -197 bp shows the presence of two repeated sequences of 9 bp [R9(1) and R9(2)] located at -226 to -203 bp. Deletions and mutations analysis of the R9 motifs significantly reduced promoter activity in trophozoites from clone C2. EMSA experiments revealed specific binding of nuclear proteins from E. histolytica to the R9 sequence. While competition assays showed that the presence of more than one R9 sequence is necessary for a strong DNA-protein interaction. Moreover, Western blot experiments with partially-purified proteins interacting with the R9 motif and antibodies against EhEBP1, recognized a 28 kDa protein. Interestingly, this antibody in supershift assays prevented the DNA-protein interactions formation, of the R9 sequences and nuclear proteins from amoeba, indicating that one of the proteins that interact with the R9 element is an EhEBP1-like one.In conclusion, we demonstrate that R9 motifs are recognized by an EhEBP1 protein and activate the EhPgp1 gene expression.