Plasmodium falciparum Nucleosomes Exhibit Reduced Stability and Lost Sequence Dependent Nucleosome Positioning.
The packaging and organization of genomic DNA into chromatin represents an additional regulatory layer of gene expression, with specific nucleosome positions that restrict the accessibility of regulatory DNA elements. The mechanisms that position nucleosomes in vivo are thought to depend on the biop...
Main Authors: | , , , , , , , |
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Format: | Article |
Language: | English |
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Public Library of Science (PLoS)
2016-12-01
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Series: | PLoS Pathogens |
Online Access: | https://doi.org/10.1371/journal.ppat.1006080 |
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author | Elisabeth Silberhorn Uwe Schwartz Patrick Löffler Samuel Schmitz Anne Symelka Tania de Koning-Ward Rainer Merkl Gernot Längst |
author_facet | Elisabeth Silberhorn Uwe Schwartz Patrick Löffler Samuel Schmitz Anne Symelka Tania de Koning-Ward Rainer Merkl Gernot Längst |
author_sort | Elisabeth Silberhorn |
collection | DOAJ |
description | The packaging and organization of genomic DNA into chromatin represents an additional regulatory layer of gene expression, with specific nucleosome positions that restrict the accessibility of regulatory DNA elements. The mechanisms that position nucleosomes in vivo are thought to depend on the biophysical properties of the histones, sequence patterns, like phased di-nucleotide repeats and the architecture of the histone octamer that folds DNA in 1.65 tight turns. Comparative studies of human and P. falciparum histones reveal that the latter have a strongly reduced ability to recognize internal sequence dependent nucleosome positioning signals. In contrast, the nucleosomes are positioned by AT-repeat sequences flanking nucleosomes in vivo and in vitro. Further, the strong sequence variations in the plasmodium histones, compared to other mammalian histones, do not present adaptations to its AT-rich genome. Human and parasite histones bind with higher affinity to GC-rich DNA and with lower affinity to AT-rich DNA. However, the plasmodium nucleosomes are overall less stable, with increased temperature induced mobility, decreased salt stability of the histones H2A and H2B and considerable reduced binding affinity to GC-rich DNA, as compared with the human nucleosomes. In addition, we show that plasmodium histone octamers form the shortest known nucleosome repeat length (155bp) in vitro and in vivo. Our data suggest that the biochemical properties of the parasite histones are distinct from the typical characteristics of other eukaryotic histones and these properties reflect the increased accessibility of the P. falciparum genome. |
first_indexed | 2024-12-19T20:21:39Z |
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institution | Directory Open Access Journal |
issn | 1553-7366 1553-7374 |
language | English |
last_indexed | 2024-12-19T20:21:39Z |
publishDate | 2016-12-01 |
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series | PLoS Pathogens |
spelling | doaj.art-ff1bd278a9044d38bbed43616969f9642022-12-21T20:07:00ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-12-011212e100608010.1371/journal.ppat.1006080Plasmodium falciparum Nucleosomes Exhibit Reduced Stability and Lost Sequence Dependent Nucleosome Positioning.Elisabeth SilberhornUwe SchwartzPatrick LöfflerSamuel SchmitzAnne SymelkaTania de Koning-WardRainer MerklGernot LängstThe packaging and organization of genomic DNA into chromatin represents an additional regulatory layer of gene expression, with specific nucleosome positions that restrict the accessibility of regulatory DNA elements. The mechanisms that position nucleosomes in vivo are thought to depend on the biophysical properties of the histones, sequence patterns, like phased di-nucleotide repeats and the architecture of the histone octamer that folds DNA in 1.65 tight turns. Comparative studies of human and P. falciparum histones reveal that the latter have a strongly reduced ability to recognize internal sequence dependent nucleosome positioning signals. In contrast, the nucleosomes are positioned by AT-repeat sequences flanking nucleosomes in vivo and in vitro. Further, the strong sequence variations in the plasmodium histones, compared to other mammalian histones, do not present adaptations to its AT-rich genome. Human and parasite histones bind with higher affinity to GC-rich DNA and with lower affinity to AT-rich DNA. However, the plasmodium nucleosomes are overall less stable, with increased temperature induced mobility, decreased salt stability of the histones H2A and H2B and considerable reduced binding affinity to GC-rich DNA, as compared with the human nucleosomes. In addition, we show that plasmodium histone octamers form the shortest known nucleosome repeat length (155bp) in vitro and in vivo. Our data suggest that the biochemical properties of the parasite histones are distinct from the typical characteristics of other eukaryotic histones and these properties reflect the increased accessibility of the P. falciparum genome.https://doi.org/10.1371/journal.ppat.1006080 |
spellingShingle | Elisabeth Silberhorn Uwe Schwartz Patrick Löffler Samuel Schmitz Anne Symelka Tania de Koning-Ward Rainer Merkl Gernot Längst Plasmodium falciparum Nucleosomes Exhibit Reduced Stability and Lost Sequence Dependent Nucleosome Positioning. PLoS Pathogens |
title | Plasmodium falciparum Nucleosomes Exhibit Reduced Stability and Lost Sequence Dependent Nucleosome Positioning. |
title_full | Plasmodium falciparum Nucleosomes Exhibit Reduced Stability and Lost Sequence Dependent Nucleosome Positioning. |
title_fullStr | Plasmodium falciparum Nucleosomes Exhibit Reduced Stability and Lost Sequence Dependent Nucleosome Positioning. |
title_full_unstemmed | Plasmodium falciparum Nucleosomes Exhibit Reduced Stability and Lost Sequence Dependent Nucleosome Positioning. |
title_short | Plasmodium falciparum Nucleosomes Exhibit Reduced Stability and Lost Sequence Dependent Nucleosome Positioning. |
title_sort | plasmodium falciparum nucleosomes exhibit reduced stability and lost sequence dependent nucleosome positioning |
url | https://doi.org/10.1371/journal.ppat.1006080 |
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