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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.
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Citation / Publisher Attribution
Nucleic Acids Research, v. 47, issue 22, p. 11574-11588
Scholar Commons Citation
Hoeijmakers, Wieteke Anna Maria; Miao, Jun; Schmidt, Sabine; Toenhake, Christa Geeke; Shrestha, Sony; Venhuizen, Jeron; Henderson, Rob; Birnbaum, Jakob; Ghidelli-Disse, Sonja; Drewes, Gerard; Cui, Liwang; Stunnenberg, Hendrik Gerard; Spielmann, Tobias; and Bártfai, Richárd, "Epigenetic Reader Complexes of the Human Malaria Parasite, Plasmodium falciparum" (2019). Internal Medicine Faculty Publications. 152.