title: The nucleosome landscape of Plasmodium falciparum reveals chromatin architecture and dynamics of regulatory sequences.
abstract: In eukaryotes, the chromatin architecture has a pivotal role in regulating all DNA-associated processes and it is central to the control of gene expression. For Plasmodium falciparum, a causative agent of human malaria, the nucleosome positioning profile of regulatory regions deserves particular attention because of their extreme AT-content. With the aid of a highly controlled MNase-seq procedure we reveal how positioning of nucleosomes provides a structural and regulatory framework to the transcriptional unit by demarcating landmark sites (transcription/translation start and end sites). In addition, our analysis provides strong indications for the function of positioned nucleosomes in splice site recognition. Transcription start sites (TSSs) are bordered by a small nucleosome-depleted region, but lack the stereotypic downstream nucleosome arrays, highlighting a key difference in chromatin organization compared to model organisms. Furthermore, we observe transcription-coupled eviction of nucleosomes on strong TSSs during intraerythrocytic development and demonstrate that nucleosome positioning and dynamics can be predictive for the functionality of regulatory DNA elements. Collectively, the strong nucleosome positioning over splice sites and surrounding putative transcription factor binding sites highlights the regulatory capacity of the nucleosome landscape in this deadly human pathogen.
authors.affiliation: Department of Molecular Biology, Radboud University, 6525GA Nijmegen, The Netherlands.
authors.forename: Philip Reiner
authors.initials: PR
authors.lastname: Kensche
authors.affiliation: Department of Molecular Biology, Radboud University, 6525GA Nijmegen, The Netherlands.
authors.forename: Wieteke Anna Maria
authors.initials: WA
authors.lastname: Hoeijmakers
authors.affiliation: Department of Molecular Biology, Radboud University, 6525GA Nijmegen, The Netherlands.
authors.forename: Christa Geeke
authors.initials: CG
authors.lastname: Toenhake
authors.affiliation: Department of Molecular Biology, Radboud University, 6525GA Nijmegen, The Netherlands.
authors.forename: Maaike
authors.initials: M
authors.lastname: Bras
authors.affiliation: Parasite Genomics Group, Wellcome Trust Sanger Institute, CB10 1SA Hinxton, UK.
authors.forename: Lia
authors.initials: L
authors.lastname: Chappell
authors.affiliation: Parasite Genomics Group, Wellcome Trust Sanger Institute, CB10 1SA Hinxton, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Berriman
authors.affiliation: Department of Molecular Biology, Radboud University, 6525GA Nijmegen, The Netherlands R.Bartfai@ncmls.ru.nl.
authors.forename: Richárd
authors.initials: R
authors.lastname: Bártfai
mesh_terms: D001482:Base Composition; D042002:Chromatin Assembly and Disassembly; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004912:Erythrocytes / Q000469:parasitology; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D007438:Introns; D008018:Life Cycle Stages / Q000235:genetics*; D009707:Nucleosomes / Q000737:chemistry* / Q000378:metabolism; D016366:Open Reading Frames; D010963:Plasmodium falciparum / Q000235:genetics* / Q000254:growth & development; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics*; D022821:RNA Splice Sites; D014157:Transcription Factors / Q000235:genetics; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D016054:DNA, Protozoan; D009707:Nucleosomes; D015800:Protozoan Proteins; D022821:RNA Splice Sites; D014157:Transcription Factors