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| Status |
Public on Jan 06, 2014 |
| Title |
Three-dimensional modeling of the P. falciparum genome during the erythrocytic cycle reveals a strong connection between genome architecture and gene expression |
| Organism |
Plasmodium falciparum 3D7 |
| Experiment type |
Other
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| Summary |
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 relation between genome architecture and gene regulation in Plasmodium, we studied the genome structure 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 observe 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 appear to be an important factor in shaping the genome architecture as they exhibit domain-like structures similar to topological domains in mammalian genomes. Midway during the cell 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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| Overall design |
Analysis of the spatial organization of the P. falciparum genome at three stages of the erythrocytic cycle using chromosome conformation capture coupled with next generation sequencing (Hi-C). As a control, we included one sample for which chromatin contacts were not preserved by crosslinking of DNA and proteins.
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| Contributor(s) |
Ay F, Bunnik EM, Varoquaux N, Bol SM, Prudhomme J, Vert J, Noble WS, Le Roch KG |
| Citation(s) |
24671853 |
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| Submission date |
Aug 26, 2013 |
| Last update date |
May 15, 2019 |
| Contact name |
Karine Le Roch |
| E-mail(s) |
karine.leroch@ucr.edu
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| Organization name |
University of California, Riverside
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| Street address |
900 University Ave
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| City |
Riverside |
| ZIP/Postal code |
92521 |
| Country |
USA |
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| Platforms (1) |
| GPL17634 |
Illumina HiSeq 2000 (Plasmodium falciparum 3D7) |
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| Samples (4)
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| GSM1215595 |
P.falciparum_3D7_18h_HiSeq_non-crosslinked_control |
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| Relations |
| BioProject |
PRJNA217090 |
| SRA |
SRP029223 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE50199_MboI-cutSites.txt.gz |
101.4 Kb |
(ftp)(http) |
TXT |
| GSE50199_RAW.tar |
17.0 Gb |
(http)(custom) |
TAR (of FASTQ, TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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