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Heterochromatin protein 1 secures survival and transmission of malaria parasites

Brancucci, Nicolas M. B. and Bertschi, Nicole L. and Zhu, Lei and Niederwieser, Igor and Chin, Wai Hoe and Wampfler, Rahel and Freymond, Céline and Rottmann, Matthias and Felger, Ingrid and Bozdech, Zbynek and Voss, Till S.. (2014) Heterochromatin protein 1 secures survival and transmission of malaria parasites. Cell host & microbe, Vol. 16, H. 2. pp. 165-176.

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Official URL: http://edoc.unibas.ch/dok/A6289125

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Abstract

Clonally variant expression of surface antigens allows the malaria parasite Plasmodium falciparum to evade immune recognition during blood stage infection and secure malaria transmission. We demonstrate that heterochromatin protein 1 (HP1), an evolutionary conserved regulator of heritable gene silencing, controls expression of numerous P. falciparum virulence genes as well as differentiation into the sexual forms that transmit to mosquitoes. Conditional depletion of P. falciparum HP1 (PfHP1) prevents mitotic proliferation of blood stage parasites and disrupts mutually exclusive expression and antigenic variation of the major virulence factor PfEMP1. Additionally, PfHP1-dependent regulation of PfAP2-G, a transcription factor required for gametocyte conversion, controls the switch from asexual proliferation to sexual differentiation, providing insight into the epigenetic mechanisms underlying gametocyte commitment. These findings show that PfHP1 is centrally involved in clonally variant gene expression and sexual differentiation in P. falciparum and have major implications for developing antidisease and transmission-blocking interventions against malaria.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Former Units within Swiss TPH > Molecular Diagnostics (Felger)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Malaria Gene Regulation (Voss)
UniBasel Contributors:Niederwieser, Igor and Rottmann, Matthias and Felger, Ingrid and Voss, Till S
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
ISSN:1931-3128
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Nov 2014 08:28
Deposited On:07 Nov 2014 08:28

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