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Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum.

ABSTRACT: Epigenetic regulatory mechanisms are central to the development and survival of all eukaryotic organisms. These mechanisms critically depend on the marking of chromatin domains with distinctive histone tail modifications (PTMs) and their recognition by effector protein complexes. Here we used quantitative proteomic approaches to unveil interactions between PTMs and associated reader protein complexes of Plasmodium falciparum, a unicellular parasite causing malaria. Histone peptide pull-downs with the most prominent and/or parasite-specific PTMs revealed the binding preference for 14 putative and novel reader proteins. Amongst others, they highlighted the acetylation-level-dependent recruitment of the BDP1/BDP2 complex and identified an PhD-finger protein (PHD 1, PF3D7_1008100) that could mediate a cross-talk between H3K4me2/3 and H3K9ac marks. Tagging and interaction proteomics of 12 identified proteins unveiled the composition of 5 major epigenetic complexes, including the elusive TBP-associated-factor complex as well as two distinct GCN5/ADA2 complexes. Furthermore, it has highlighted a remarkable degree of interaction between these five (sub)complexes. Collectively, this study provides an extensive inventory of PTM-reader interactions and composition of epigenetic complexes. It will not only fuel further explorations of gene regulation amongst ancient eukaryotes, but also provides a stepping stone for exploration of PTM-reader interactions for antimalarial drug development.

SUBMITTER: Hoeijmakers WAM

PROVIDER: S-EPMC7145593 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum

Project description:Epigenetic regulatory mechanisms are central to the development and survival of all eukaryotic organisms. These mechanisms critically depend on the marking of chromatin domains with distinctive histone tail modifications (PTMs) and their recognition by effector protein complexes. In this project, histone peptide pull-downs and protein-protein interaction quantitative proteomics were used to unveil interactions between PTMs and associated reader protein complexes of Plasmodium falciparum, a unicellular parasite causing malaria. One of the identified bromodomain proteins (BDP5, PF3D7_1234100) has previously been proposed to be the P. falciparum homologue of TBP-associated factor 1 (TAF1). As the bdp5/taf1 locus was refractory to disruption, knock-sideways strategy was employed to disrupt BDP5/TAF1 function by tethering it to the cell membrane (Birnbaum, 2017, Nature Methods). To gain insight in the transcriptional defects upon BDP5/TAF1 knock-sideways (KS), directional RNA seq libraries were generated at 2, 6 and 12 hours after knock-sideways induction.

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Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum

Project description:Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum

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The Variantome of the malaria parasite Plasmodium falciparum.

Project description:We compared transcript levels at several points along the asexual blood cycle between 21 P. falciparum lines. These 21 parasite lines are organized in 4 sets of parasite lines, with all parasite lines within a set sharing a clonal origin. We compared transcript levels within each set. We also performed comparative genome hybridization (CGH) for all 21 parasite lines.

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The mRNA-bound proteome of the human malaria parasite Plasmodium falciparum.

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