Mechanisms of gene regulation in Plasmodium.

Summary. Recent investigations into gene expression in malarial systems suggest that locus-specific, promoter-based transcriptional control is not the dominant mode of regulation in Plasmodium . Although global transcript and protein profiles across the life cycle of Plasmodium imply significant control of developmental progression, 1,2 the exact mechanisms underlying this pattern are largely unknown, and appear to be unconventional compared with those of most model organisms. As such, our understanding of transcriptional, post-transcriptional, and epigenetic mechanisms in Plasmodium , as well as their relative contributions to gene regulation, lags far behind that of other eukaryotic systems. We seek a comprehensive characterization of the mechanisms that Plasmodium species have evolved to control gene expression during their complex life cycles. Both the integration in a and types Preliminary further delineation of the genomic structure, as well as elucidation of chromatin structure and epigenetic features; a systematic comparison of global expression data from nuclear run-on, RNA expression microarrays, and proteomic based assays; and the re-evaluation and functional testing of putative regulatory nucleic acid motifs, including characterization of their binding proteins. Detailed examina-tion of regulation on a whole-genome scale, as well as among specific loci, will ultimately make way for control measures aimed at interfering with processes crucial for parasite sur-vival, such as differentiation, antigenic variation, and development of