title: 3D nuclear architecture reveals coupled cell cycle dynamics of chromatin and nuclear pores in the malaria parasite Plasmodium falciparum.
abstract: The deadliest form of human malaria is caused by the protozoan parasite Plasmodium falciparum. The complex life cycle of this parasite is associated with tight transcriptional regulation of gene expression. Nuclear positioning and chromatin dynamics may play an important role in regulating P. falciparum virulence genes. We have applied an emerging technique of electron microscopy to construct a 3D model of the parasite nucleus at distinct stages of development within the infected red blood cell. We have followed the distribution of nuclear pores and chromatin throughout the intra-erythrocytic cycle, and have found a striking coupling between the distributions of nuclear pores and chromatin organization. Pore dynamics involve clustering, biogenesis, and division among daughter cells, while chromatin undergoes stage-dependent changes in packaging. Dramatic changes in heterochromatin distribution coincide with a previously identified transition in gene expression and nucleosome positioning during the mid-to-late schizont phase. We also found a correlation between euchromatin positioning at the nuclear envelope and the local distribution of nuclear pores, as well as a dynamic nuclear polarity during schizogony. These results suggest that cyclic patterns in gene expression during parasite development correlate with gross changes in cellular and nuclear architecture.
authors.affiliation: Department of Microbiology and Molecular Genetics, The Kuvin Center for the Study of Infectious and Tropical Diseases, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Allon
authors.initials: A
authors.lastname: Weiner
authors.forename: Noa
authors.initials: N
authors.lastname: Dahan-Pasternak
authors.forename: Eyal
authors.initials: E
authors.lastname: Shimoni
authors.forename: Vera
authors.initials: V
authors.lastname: Shinder
authors.forename: Palle
authors.initials: P
authors.lastname: von Huth
authors.forename: Michael
authors.initials: M
authors.lastname: Elbaum
authors.forename: Ron
authors.initials: R
authors.lastname: Dzikowski
mesh_terms: D000818:Animals; D002453:Cell Cycle; D002467:Cell Nucleus / Q000648:ultrastructure*; D002843:Chromatin / Q000378:metabolism* / Q000648:ultrastructure*; D004912:Erythrocytes / Q000469:parasitology; D015870:Gene Expression; D006801:Humans; D021621:Imaging, Three-Dimensional; D008854:Microscopy, Electron; D009685:Nuclear Envelope / Q000648:ultrastructure; D022022:Nuclear Pore / Q000378:metabolism* / Q000648:ultrastructure*; D010963:Plasmodium falciparum / Q000502:physiology / Q000648:ultrastructure*
chemical_list: D002843:Chromatin