title: H3.3 demarcates GC-rich coding and subtelomeric regions and serves as potential memory mark for virulence gene expression in Plasmodium falciparum.
abstract: Histones, by packaging and organizing the DNA into chromatin, serve as essential building blocks for eukaryotic life. The basic structure of the chromatin is established by four canonical histones (H2A, H2B, H3 and H4), while histone variants are more commonly utilized to alter the properties of specific chromatin domains. H3.3, a variant of histone H3, was found to have diverse localization patterns and functions across species but has been rather poorly studied in protists. Here we present the first genome-wide analysis of H3.3 in the malaria-causing, apicomplexan parasite, P. falciparum, which revealed a complex occupancy profile consisting of conserved and parasite-specific features. In contrast to other histone variants, PfH3.3 primarily demarcates euchromatic coding and subtelomeric repetitive sequences. Stable occupancy of PfH3.3 in these regions is largely uncoupled from the transcriptional activity and appears to be primarily dependent on the GC-content of the underlying DNA. Importantly, PfH3.3 specifically marks the promoter region of an active and poised, but not inactive antigenic variation (var) gene, thereby potentially contributing to immune evasion. Collectively, our data suggest that PfH3.3, together with other histone variants, indexes the P. falciparum genome to functionally distinct domains and contribute to a key survival strategy of this deadly pathogen.
authors.affiliation: Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands.
authors.forename: Sabine Anne-Kristin
authors.initials: SA
authors.lastname: Fraschka
authors.affiliation: Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands.
authors.forename: Rob Wilhelmus Maria
authors.initials: RW
authors.lastname: Henderson
authors.affiliation: Department of Molecular Biology, Radboud University, Nijmegen, the Netherlands.
authors.forename: Richárd
authors.initials: R
authors.lastname: Bártfai
mesh_terms: D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D016054:DNA, Protozoan / Q000737:chemistry / Q000378:metabolism; D020862:GC Rich Sequence; D015723:Gene Library; D018503:Genome, Protozoan; D059014:High-Throughput Nucleotide Sequencing; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008018:Life Cycle Stages; D010963:Plasmodium falciparum / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity*; D011401:Promoter Regions, Genetic; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016053:RNA, Protozoan / Q000737:chemistry / Q000378:metabolism; D017423:Sequence Analysis, RNA; D014774:Virulence / Q000235:genetics*
chemical_list: D002843:Chromatin; D016054:DNA, Protozoan; D006657:Histones; D015800:Protozoan Proteins; D016053:RNA, Protozoan; C085731:erythrocyte membrane protein 1, Plasmodium falciparum