期刊
GENOME RESEARCH
卷 24, 期 6, 页码 974-988出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gr.169417.113
关键词
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资金
- Computing Research Association CIFellows award (NSF award) [CIF 1136996]
- Human Frontier Science Program [LT000507/2011]
- National Institutes of Health [R01 AI85077-01A1, R01 AI106775-01]
- European Research Council [SMAC-ERC-280032]
- European Commission [HEALTH-F5-2012-305626]
- French National Research Agency [ANR-11-BINF-0001]
- Agence Nationale de la Recherche (ANR) [ANR-11-BINF-0001] Funding Source: Agence Nationale de la Recherche (ANR)
The development of the human malaria parasite Plasmodium falciparum is controlled by coordinated changes in gene expression throughout its complex life cycle, but the corresponding regulatory mechanisms are incompletely understood. To study the relationship between genome architecture and gene regulation in Plasmodium, we assayed the genome architecture of P. falciparum at three time points during its erythrocytic (asexual) cycle. Using chromosome conformation capture coupled with next-generation sequencing technology (Hi-C), we obtained high-resolution chromosomal contact maps, which we then used to construct a consensus three-dimensional genome structure for each time point. We observed strong clustering of centromeres, telomeres, ribosomal DNA, and virulence genes, resulting in a complex architecture that cannot be explained by a simple volume exclusion model. Internal virulence gene clusters exhibit domain-like structures in contact maps, suggesting that they play an important role in the genome architecture. Midway during the erythrocytic cycle, at the highly transcriptionally active trophozoite stage, the genome adopts a more open chromatin structure with increased chromosomal intermingling. In addition, we observed reduced expression of genes located in spatial proximity to the repressive subtelomeric center, and colocalization of distinct groups of parasite-specific genes with coordinated expression profiles. Overall, our results are indicative of a strong association between the P. falciparum spatial genome organization and gene expression. Understanding the molecular processes involved in genome conformation dynamics could contribute to the discovery of novel antimalarial strategies.
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