title: Quantitative chromatin proteomics reveals a dynamic histone post-translational modification landscape that defines asexual and sexual Plasmodium falciparum parasites.
abstract: Gene expression in Plasmodia integrates post-transcriptional regulation with epigenetic marking of active genomic regions through histone post-translational modifications (PTMs). To generate insights into the importance of histone PTMs to the entire asexual and sexual developmental cycles of the parasite, we used complementary and comparative quantitative chromatin proteomics to identify and functionally characterise histone PTMs in 8 distinct life cycle stages of P. falciparum parasites. ~500 individual histone PTMs were identified of which 106 could be stringently validated. 46 individual histone PTMs and 30 co-existing PTMs were fully quantified with high confidence. Importantly, 15 of these histone PTMs are novel for Plasmodia (e.g. H3K122ac, H3K27me3, H3K56me3). The comparative nature of the data revealed a highly dynamic histone PTM landscape during life cycle development, with a set of histone PTMs (H3K4ac, H3K9me1 and H3K36me2) displaying a unique and conserved abundance profile exclusively during gametocytogenesis (P < 0.001). Euchromatic histone PTMs are abundant during schizogony and late gametocytes; heterochromatic PTMs mark early gametocytes. Collectively, this data provides the most accurate, complete and comparative chromatin proteomic analyses of the entire life cycle development of malaria parasites. A substantial association between histone PTMs and stage-specific transition provides insights into the intricacies characterising Plasmodial developmental biology.
authors.affiliation: Department of Biochemistry, Institute for Sustainable Malaria Control, University of Pretoria, Private bag x20, Hatfield, Pretoria, South Africa.
authors.forename: Nanika
authors.initials: N
authors.lastname: Coetzee
authors.affiliation: Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Simone
authors.initials: S
authors.lastname: Sidoli
authors.affiliation: Department of Biochemistry, Institute for Sustainable Malaria Control, University of Pretoria, Private bag x20, Hatfield, Pretoria, South Africa.
authors.forename: Riëtte
authors.identifier: http://orcid.org/0000-0002-1710-0441
authors.initials: R
authors.lastname: van Biljon
authors.affiliation: Department of Biochemistry & Molecular Biology and Centre for Malaria Research, Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Heather
authors.initials: H
authors.lastname: Painter
authors.affiliation: Department of Biochemistry & Molecular Biology and Centre for Malaria Research, Pennsylvania State University, University Park, Pennsylvania, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Llinás
authors.affiliation: Epigenetics Program, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Benjamin A
authors.initials: BA
authors.lastname: Garcia
authors.affiliation: Department of Biochemistry, Institute for Sustainable Malaria Control, University of Pretoria, Private bag x20, Hatfield, Pretoria, South Africa. lbirkholtz@up.ac.za.
authors.forename: Lyn-Marie
authors.identifier: http://orcid.org/0000-0001-5888-2905
authors.initials: LM
authors.lastname: Birkholtz
mesh_terms: D000595:Amino Acid Sequence; D002843:Chromatin / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020869:Gene Expression Profiling; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D008018:Life Cycle Stages; D010963:Plasmodium falciparum / Q000254:growth & development / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods; D059467:Transcriptome
chemical_list: D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones