Three-dimensional modeling of the P. falciparum genome during the erythrocytic cycle reveals a strong connection between genome architecture and gene expression

摘要: The development of the human malaria parasite Plasmodium falciparum is controlled by coordinated changes in gene expression throughout its complex life cycle, but corresponding regulatory mechanisms are incompletely understood. To study relationship between genome architecture and regulation Plasmodium, we assayed P. at three time points during erythrocytic (asexual) cycle. Using chromosome conformation capture coupled with next-generation sequencing technology (Hi-C), obtained high-resolution chromosomal contact maps, which then used to construct a consensus three-dimensional structure for each point. We observed strong clustering centromeres, telomeres, ribosomal DNA, virulence genes, resulting that cannot be explained simple volume exclusion model. Internal clusters exhibit domain-like structures suggesting they play an important role architecture. Midway highly transcriptionally active trophozoite stage, adopts more open chromatin increased intermingling. In addition, reduced genes located spatial proximity repressive subtelomeric center, colocalization distinct groups parasite-specific profiles. Overall, our results indicative association organization expression. Understanding molecular processes involved dynamics could contribute discovery novel antimalarial strategies.