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Cell Host Microbe. 2018 Mar 14;23(3):407-420.e8. doi: 10.1016/j.chom.2018.01.008. Epub 2018 Mar 1.

Comparative Heterochromatin Profiling Reveals Conserved and Unique Epigenome Signatures Linked to Adaptation and Development of Malaria Parasites.

Author information

1
Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands.
2
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland; University of Basel, 4001 Basel, Switzerland.
3
School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore.
4
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8QQ, UK; Department of Immunology and Infectious Diseases, Harvard TH Chan School of Public Health, Boston, MA 02155, USA.
5
Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
6
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot 63110, Thailand.
7
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot 63110, Thailand; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine Research Building, University of Oxford Old Road Campus, Oxford OX3 7FZ, UK.
8
Department of Microbiology and Immunology, University of Otago, Dunedin 9054, New Zealand.
9
Department of Molecular Biology, Faculty of Science, Radboud University, 6525 GA Nijmegen, the Netherlands. Electronic address: r.bartfai@science.ru.nl.
10
Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4051 Basel, Switzerland; University of Basel, 4001 Basel, Switzerland. Electronic address: till.voss@swisstph.ch.

Abstract

Heterochromatin-dependent gene silencing is central to the adaptation and survival of Plasmodium falciparum malaria parasites, allowing clonally variant gene expression during blood infection in humans. By assessing genome-wide heterochromatin protein 1 (HP1) occupancy, we present a comprehensive analysis of heterochromatin landscapes across different Plasmodium species, strains, and life cycle stages. Common targets of epigenetic silencing include fast-evolving multi-gene families encoding surface antigens and a small set of conserved HP1-associated genes with regulatory potential. Many P. falciparum heterochromatic genes are marked in a strain-specific manner, increasing the parasite's adaptive capacity. Whereas heterochromatin is strictly maintained during mitotic proliferation of asexual blood stage parasites, substantial heterochromatin reorganization occurs in differentiating gametocytes and appears crucial for the activation of key gametocyte-specific genes and adaptation of erythrocyte remodeling machinery. Collectively, these findings provide a catalog of heterochromatic genes and reveal conserved and specialized features of epigenetic control across the genus Plasmodium.

KEYWORDS:

HP1; Plasmodium; antigenic variation; epigenetics; gametocytes; gene silencing; heterochromatin; host-parasite interaction; malaria; sexual differentiation

PMID:
29503181
PMCID:
PMC5853956
DOI:
10.1016/j.chom.2018.01.008
[Indexed for MEDLINE]
Free PMC Article

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