Plasmodium falciparum Nucleosomes Exhibit Reduced Stability and Lost Sequence Dependent Nucleosome Positioning

PLoS Pathogens

Samuel Schmitz¹  Tania de Koning-Ward¹  Uwe Schwartz¹  Gernot Längst¹  Rainer Merkl²  Anne Symelka²  Elisabeth Silberhorn³  Patrick Löffler³ 

[1] Biochemistry Centre Regensburg (BCR), University of Regensburg, Regensburg, Germany;Biochemistry II;Biochemistry III;School of Medicine, Deakin University, Waurn Ponds, Australia

关键词: Nucleosomes;    Histones;    Plasmodium;    DNA sequence analysis;    Chromatin;    Plasmodium falciparum;    Sequence motif analysis;    Sequence assembly tools;   

DOI  :  10.1371/journal.ppat.1006080

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY