In trying to understand how the human malaria parasite (Plasmodium falciparum) multiplies in red blood cells, a research team has discovered that a kind of "histone crash" takes place--a massive breakdown of the chromatin architecture that explains how the parasite can extensively and rapidly replicate its DNA and coding genes. "If this mechanism can be stopped," said Dr. Karine Le Roch, an assistant professor of cell biology and neuroscience at the University of California-Riverside, and senior author of the report, "Plasmodium replication would cease or be severely inhibited, thus controlling the spread of malaria." "Dr. Le Roch's findings document a global mechanism mediating significant changes in gene expression as the parasites transition through developmental stages in the human hosts," said Dr. Anthony A. James, a distinguished professor of microbiology & molecular genetics and molecular biology & biochemistry at the University of California-Irvine, who was not involved in the research. "As well as being a major basic discovery, this provides a basis for probing the mechanisms for novel drug development." The current study was spurred, in part, by an earlier observation that, in Plasmodium falciparum, specific transcription factors are apparently under-represented relative to the size of the parasite’s genome, and by the fact that mechanisms underlying transcriptional regulation in Plasmodium have remained controversial. “Our results demonstrate that the processes driving gene expression in Plasmodium challenge the classical eukaryotic model of transcriptional regulation occurring mostly at the transcription initiation level. We found in our experiments that histones are massively evicted everywhere in the Plasmodium genome, resulting in most of the Plasmodium genes to be transcribed at once," said Dr. La Roch.
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