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5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites
In the human malaria parasite Plasmodium falciparum antigenic variation facilitates long-term chronic infection of the host. This is achieved by sequential expression of a single member of the 60-member var family. Here we show that the 5′ flanking region nucleates epigenetic events strongly linked...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Blackwell Publishing Ltd
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228885/ https://www.ncbi.nlm.nih.gov/pubmed/18028313 http://dx.doi.org/10.1111/j.1365-2958.2007.06009.x |
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author | Lopez-Rubio, Jose Juan Gontijo, Alisson M Nunes, Marta C Issar, Neha Hernandez Rivas, Rosaura Scherf, Artur |
author_facet | Lopez-Rubio, Jose Juan Gontijo, Alisson M Nunes, Marta C Issar, Neha Hernandez Rivas, Rosaura Scherf, Artur |
author_sort | Lopez-Rubio, Jose Juan |
collection | PubMed |
description | In the human malaria parasite Plasmodium falciparum antigenic variation facilitates long-term chronic infection of the host. This is achieved by sequential expression of a single member of the 60-member var family. Here we show that the 5′ flanking region nucleates epigenetic events strongly linked to the maintenance of mono-allelic var gene expression pattern during parasite proliferation. Tri- and dimethylation of histone H3 lysine 4 peak in the 5′ upstream region of transcribed var and during the poised state (non-transcribed phase of var genes during the 48 h asexual life cycle), ‘bookmarking’ this member for re-activation at the onset of the next cycle. Histone H3 lysine 9 trimethylation acts as an antagonist to lysine 4 methylation to establish stably silent var gene states along the 5′ flanking and coding region. Furthermore, we show that competition exists between H3K9 methylation and H3K9 acetylation in the 5′ flanking region and that these marks contribute epigenetically to repressing or activating var gene expression. Our work points to a pivotal role of the histone methyl mark writing and reading machinery in the phenotypic inheritance of virulence traits in the malaria parasite. |
format | Text |
id | pubmed-2228885 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Blackwell Publishing Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-22288852008-02-13 5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites Lopez-Rubio, Jose Juan Gontijo, Alisson M Nunes, Marta C Issar, Neha Hernandez Rivas, Rosaura Scherf, Artur Mol Microbiol Research Articles In the human malaria parasite Plasmodium falciparum antigenic variation facilitates long-term chronic infection of the host. This is achieved by sequential expression of a single member of the 60-member var family. Here we show that the 5′ flanking region nucleates epigenetic events strongly linked to the maintenance of mono-allelic var gene expression pattern during parasite proliferation. Tri- and dimethylation of histone H3 lysine 4 peak in the 5′ upstream region of transcribed var and during the poised state (non-transcribed phase of var genes during the 48 h asexual life cycle), ‘bookmarking’ this member for re-activation at the onset of the next cycle. Histone H3 lysine 9 trimethylation acts as an antagonist to lysine 4 methylation to establish stably silent var gene states along the 5′ flanking and coding region. Furthermore, we show that competition exists between H3K9 methylation and H3K9 acetylation in the 5′ flanking region and that these marks contribute epigenetically to repressing or activating var gene expression. Our work points to a pivotal role of the histone methyl mark writing and reading machinery in the phenotypic inheritance of virulence traits in the malaria parasite. Blackwell Publishing Ltd 2007-12 2007-11-19 /pmc/articles/PMC2228885/ /pubmed/18028313 http://dx.doi.org/10.1111/j.1365-2958.2007.06009.x Text en © 2007 The Authors Journal compilation © 2007 Blackwell Publishing Ltd https://creativecommons.org/licenses/by/2.5/ Re-use of this article is permitted in accordance with the Creative Commons Deed, Attribution 2.5, which does not permit commercial exploitation. |
spellingShingle | Research Articles Lopez-Rubio, Jose Juan Gontijo, Alisson M Nunes, Marta C Issar, Neha Hernandez Rivas, Rosaura Scherf, Artur 5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites |
title | 5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites |
title_full | 5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites |
title_fullStr | 5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites |
title_full_unstemmed | 5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites |
title_short | 5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites |
title_sort | 5′ flanking region of var genes nucleate histone modification patterns linked to phenotypic inheritance of virulence traits in malaria parasites |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2228885/ https://www.ncbi.nlm.nih.gov/pubmed/18028313 http://dx.doi.org/10.1111/j.1365-2958.2007.06009.x |
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