• Open Access

H2A.Z/H2B.Z double-variant nucleosomes inhabit the AT-rich promoter regions of the Plasmodium falciparum genome

Authors

  • Wieteke A. M. Hoeijmakers,

    1. Department of Molecular Biology, Radboud University, Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands
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  • Adriana M. Salcedo-Amaya,

    1. Department of Molecular Biology, Radboud University, Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands
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  • Arne H. Smits,

    1. Department of Molecular Biology, Radboud University, Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands
    Current affiliation:
    1. Department of Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands
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  • Kees-Jan Françoijs,

    1. Department of Molecular Biology, Radboud University, Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands
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  • Moritz Treeck,

    1. Malaria Group, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany
    Current affiliation:
    1. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA
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  • Tim-Wolf Gilberger,

    1. Malaria Group, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany
    2. Pathology and Molecular Medicine, M.G. DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON, Canada
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  • Hendrik G. Stunnenberg,

    Corresponding author
    1. Department of Molecular Biology, Radboud University, Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands
    • Department of Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands
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  • Richárd Bártfai

    Corresponding author
    1. Department of Molecular Biology, Radboud University, Nijmegen Centre for Molecular Life Sciences, Nijmegen, the Netherlands
    • Department of Molecular Cancer Research, University Medical Center Utrecht, Utrecht, the Netherlands
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For correspondence. E-mail R.Bartfai@ncmls.ru.nl or H.Stunnenberg@ncmls.ru.nl; Tel. (+31) 24 3610523; Fax (+31) 24 3610520.

Summary

Histone variants are key components of the epigenetic code and evolved to perform specific functions in transcriptional regulation, DNA repair, chromosome segregation and other fundamental processes. Although variants for histone H2A and H3 are found throughout the eukaryotic kingdom, variants of histone H2B and H4 are rarely encountered. H2B.Z is one of those rare H2B variants and is apicomplexan-specific. Here we show that in Plasmodium falciparum H2B.Z localizes to euchromatic intergenic regions throughout intraerythrocytic development and together with H2A.Z forms a double-variant nucleosome subtype. These nucleosomes are enriched in promoters over 3′ intergenic regions and their occupancy generally correlates with the strength of the promoter, but not with its temporal activity. Remarkably, H2B.Z occupancy levels exhibit a clear correlation with the base-composition of the underlying DNA, raising the intriguing possibility that the extreme AT content of the intergenic regions within the Plasmodium genome might be instructive for histone variant deposition. In summary, our data show that the H2A.Z/H2B.Z double-variant nucleosome demarcates putative regulatory regions of the P. falciparum epigenome and likely provides a scaffold for dynamic regulation of gene expression in this deadly human pathogen.

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