Transcriptional regulation mechanism of Plasmodium spp. parasites.
The life cycle of Plasmodium parasites is complicated; they invade into the host and mosquito cells accompanied by the morphological changes, multiply into more than thousands of daughter parasites, and fertilize after the sexual development. In each developmental stage, several hundreds of genes express specifically and are responsible for the characteristic features of parasites at each stage, such as merozoite, ookinete, sporozoite, and gametocytes, e.t.c. However, transcriptional activation factors had not been identified even after the completion of genome sequencing, and the regulation of gene expressions had thus remained to be unclear.
In 2005, S. Balaji et.al. suggested based on the computational analysis that there were the protein family, which consists of 27 members containing the plant-origin DNA binding domain, AP2 domain, in the genomes of Plasmodium spp. parasites. Following this, we provided the experimental evidences by the molecular genetic approach that these molecules acted as the transcriptional activation factors: these AP2 transcriptional factors expressed stage-specifically, recognized the unique DNA sequence motives, and the gene targeting of them decreased the expression of a number of genes in each developmental stage. These DNA sequence motives were commonly found at the upstream region of those down-regulated genes, suggesting that they would be the cis-elements. Furthermore, our ChIP-seq analysis showed that the AP2 transcription factor bound to upstream regions of approximately 500 genes, which correspond to 10% of all parasites’ genes, suggesting that single AP2 transcription factor would activated directly more than several hundreds of genes. This result suggested that Plasmodium spp. parasites express small number of AP2 transcription factors specifically in each stage and regulate probably all genes, which are required for the development in the stages, using them. By this mechanisms, although there are only 27 transcription factors, the parasites would be able to have the complicated life cycles. In this talk, I will show the function of AP2 transcription factors in several developmental stages and would like to discuss about the future study of transcriptional regulation of Plasmodium spp. parasites.