TY - JOUR
T1 - Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum
AU - Hoeijmakers, Wieteke Anna Maria
AU - Miao, Jun
AU - Schmidt, Sabine
AU - Toenhake, Christa Geeke
AU - Shrestha, Sony
AU - Venhuizen, Jeron
AU - Henderson, Rob
AU - Birnbaum, Jakob
AU - Ghidelli-Disse, Sonja
AU - Drewes, Gerard
AU - Cui, Liwang
AU - Stunnenberg, Hendrik Gerard
AU - Spielmann, Tobias
AU - Bártfai, Richárd
N1 - Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2019/12/16
Y1 - 2019/12/16
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85076329330&partnerID=8YFLogxK
U2 - 10.1093/nar/gkz1044
DO - 10.1093/nar/gkz1044
M3 - Article
C2 - 31728527
AN - SCOPUS:85076329330
SN - 0305-1048
VL - 47
SP - 11574
EP - 11588
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 22
ER -