Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.

Epigenetic processes are the main conductors of phenotypic variation in eukaryotes. The malaria parasite Plasmodium falciparum employs antigenic variation of the major surface antigen PfEMP1, encoded by 60 var genes, to evade acquired immune responses. Antigenic variation of PfEMP1 occurs through in...

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Autores principales:	Christian Flueck, Richard Bartfai, Jennifer Volz, Igor Niederwieser, Adriana M Salcedo-Amaya, Blaise T F Alako, Florian Ehlgen, Stuart A Ralph, Alan F Cowman, Zbynek Bozdech, Hendrik G Stunnenberg, Till S Voss
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e1d2f463331d449e97b5a27061d5a101
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spelling	oai:doaj.org-article:e1d2f463331d449e97b5a27061d5a1012021-11-25T05:47:40ZPlasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.1553-73661553-737410.1371/journal.ppat.1000569https://doaj.org/article/e1d2f463331d449e97b5a27061d5a1012009-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19730695/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Epigenetic processes are the main conductors of phenotypic variation in eukaryotes. The malaria parasite Plasmodium falciparum employs antigenic variation of the major surface antigen PfEMP1, encoded by 60 var genes, to evade acquired immune responses. Antigenic variation of PfEMP1 occurs through in situ switches in mono-allelic var gene transcription, which is PfSIR2-dependent and associated with the presence of repressive H3K9me3 marks at silenced loci. Here, we show that P. falciparum heterochromatin protein 1 (PfHP1) binds specifically to H3K9me3 but not to other repressive histone methyl marks. Based on nuclear fractionation and detailed immuno-localization assays, PfHP1 constitutes a major component of heterochromatin in perinuclear chromosome end clusters. High-resolution genome-wide chromatin immuno-precipitation demonstrates the striking association of PfHP1 with virulence gene arrays in subtelomeric and chromosome-internal islands and a high correlation with previously mapped H3K9me3 marks. These include not only var genes, but also the majority of P. falciparum lineage-specific gene families coding for exported proteins involved in host-parasite interactions. In addition, we identified a number of PfHP1-bound genes that were not enriched in H3K9me3, many of which code for proteins expressed during invasion or at different life cycle stages. Interestingly, PfHP1 is absent from centromeric regions, implying important differences in centromere biology between P. falciparum and its human host. Over-expression of PfHP1 results in an enhancement of variegated expression and highlights the presence of well-defined heterochromatic boundaries. In summary, we identify PfHP1 as a major effector of virulence gene silencing and phenotypic variation. Our results are instrumental for our understanding of this widely used survival strategy in unicellular pathogens.Christian FlueckRichard BartfaiJennifer VolzIgor NiederwieserAdriana M Salcedo-AmayaBlaise T F AlakoFlorian EhlgenStuart A RalphAlan F CowmanZbynek BozdechHendrik G StunnenbergTill S VossPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 5, Iss 9, p e1000569 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Christian Flueck Richard Bartfai Jennifer Volz Igor Niederwieser Adriana M Salcedo-Amaya Blaise T F Alako Florian Ehlgen Stuart A Ralph Alan F Cowman Zbynek Bozdech Hendrik G Stunnenberg Till S Voss Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.
description	Epigenetic processes are the main conductors of phenotypic variation in eukaryotes. The malaria parasite Plasmodium falciparum employs antigenic variation of the major surface antigen PfEMP1, encoded by 60 var genes, to evade acquired immune responses. Antigenic variation of PfEMP1 occurs through in situ switches in mono-allelic var gene transcription, which is PfSIR2-dependent and associated with the presence of repressive H3K9me3 marks at silenced loci. Here, we show that P. falciparum heterochromatin protein 1 (PfHP1) binds specifically to H3K9me3 but not to other repressive histone methyl marks. Based on nuclear fractionation and detailed immuno-localization assays, PfHP1 constitutes a major component of heterochromatin in perinuclear chromosome end clusters. High-resolution genome-wide chromatin immuno-precipitation demonstrates the striking association of PfHP1 with virulence gene arrays in subtelomeric and chromosome-internal islands and a high correlation with previously mapped H3K9me3 marks. These include not only var genes, but also the majority of P. falciparum lineage-specific gene families coding for exported proteins involved in host-parasite interactions. In addition, we identified a number of PfHP1-bound genes that were not enriched in H3K9me3, many of which code for proteins expressed during invasion or at different life cycle stages. Interestingly, PfHP1 is absent from centromeric regions, implying important differences in centromere biology between P. falciparum and its human host. Over-expression of PfHP1 results in an enhancement of variegated expression and highlights the presence of well-defined heterochromatic boundaries. In summary, we identify PfHP1 as a major effector of virulence gene silencing and phenotypic variation. Our results are instrumental for our understanding of this widely used survival strategy in unicellular pathogens.
format	article
author	Christian Flueck Richard Bartfai Jennifer Volz Igor Niederwieser Adriana M Salcedo-Amaya Blaise T F Alako Florian Ehlgen Stuart A Ralph Alan F Cowman Zbynek Bozdech Hendrik G Stunnenberg Till S Voss
author_facet	Christian Flueck Richard Bartfai Jennifer Volz Igor Niederwieser Adriana M Salcedo-Amaya Blaise T F Alako Florian Ehlgen Stuart A Ralph Alan F Cowman Zbynek Bozdech Hendrik G Stunnenberg Till S Voss
author_sort	Christian Flueck
title	Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.
title_short	Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.
title_full	Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.
title_fullStr	Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.
title_full_unstemmed	Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.
title_sort	plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/e1d2f463331d449e97b5a27061d5a101
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Plasmodium falciparum heterochromatin protein 1 marks genomic loci linked to phenotypic variation of exported virulence factors.

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