Format

Send to

Choose Destination

See 1 citation found by title matching your search:

See comment in PubMed Commons below
Genome Res. 2014 Jun;24(6):974-88. doi: 10.1101/gr.169417.113. Epub 2014 Mar 26.

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

Author information

1
Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA;
2
Department of Cell Biology and Neuroscience, University of California, Riverside, California 92521, USA;
3
Centre for Computational Biology, Mines ParisTech, Fontainebleau F-77300, France; Institut Curie, Paris F-75248, France; U900, INSERM, Paris F-75248, France;
4
Department of Genome Sciences, University of Washington, Seattle, Washington 98195, USA; Department of Computer Science and Engineering, University of Washington, Seattle, Washington 98195, USA.

Abstract

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.

PMID:
24671853
PMCID:
PMC4032861
DOI:
10.1101/gr.169417.113
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center