title: Plasmodium falciparum Nucleosomes Exhibit Reduced Stability and Lost Sequence Dependent Nucleosome Positioning.
abstract: 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.
authors.affiliation: Biochemistry III; Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Silberhorn
authors.affiliation: Biochemistry III; Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Schwartz
authors.affiliation: Biochemistry II; Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany.
authors.forename: Patrick
authors.identifier: http://orcid.org/0000-0003-0580-8239
authors.initials: P
authors.lastname: Löffler
authors.affiliation: Biochemistry II; Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany.
authors.forename: Samuel
authors.identifier: http://orcid.org/0000-0001-5314-6095
authors.initials: S
authors.lastname: Schmitz
authors.affiliation: Biochemistry III; Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Symelka
authors.affiliation: School of Medicine, Deakin University, Waurn Ponds, Australia.
authors.forename: Tania
authors.initials: T
authors.lastname: de Koning-Ward
authors.affiliation: Biochemistry II; Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany.
authors.forename: Rainer
authors.identifier: http://orcid.org/0000-0002-3521-2957
authors.initials: R
authors.lastname: Merkl
authors.affiliation: Biochemistry III; Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany.
authors.forename: Gernot
authors.initials: G
authors.lastname: Längst
mesh_terms: D016054:DNA, Protozoan / Q000737:chemistry*; D024202:Electrophoretic Mobility Shift Assay; D005786:Gene Expression Regulation / Q000235:genetics; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008958:Models, Molecular; D009707:Nucleosomes / Q000737:chemistry* / Q000235:genetics*; D010963:Plasmodium falciparum / Q000737:chemistry* / Q000235:genetics*; D016133:Polymerase Chain Reaction
chemical_list: D016054:DNA, Protozoan; D009707:Nucleosomes