Proteomics

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Plasmodium falciparum SET10 is a histone H3 lysine K18 methyltransferase regulating nucleic acid metabolic processes during intraerythrocytic development


ABSTRACT: Lifecycle progression of the malaria parasite Plasmodium falciparum requires a finely tuned regulation of gene expression including histone methylation. The histone methyltransferase PfSET10 was previously identified as a histone H3 lysine K4 methyltransferase involved in var gene regulation, making it a prominent antimalarial target. We here investigated the role of PfSET10 in the P. falciparum blood stages in more detail, using tagged PfSET10-knockout (KO) and -knockdown (KD) lines. We demonstrated a nuclear localization of PfSET10 in the P. falciparum blood stages with peak protein levels in schizonts. PfSET10 deficiency resulted in reduced intraerythrocytic growth, but had no effect on gametocyte formation. When the PfSET10-KO line was screened for histone methylation variations, lack of PfSET10 rendered the parasites unable to mark H3K18me1, while no significant changes in the H3K4 methylation status were observed. Comparative transcriptomic profiling of PfSET10-KO schizonts demonstrated the up-regulation of transcripts particularly encoding proteins of erythrocyte invasion and multi gene family proteins, suggesting a suppressive function of the histone methylation mark. TurboID coupled with mass spectrometry further revealed an extensive nuclear PfSET10 interaction network with roles in transcriptional regulation, DNA replication and repair, chromatin remodeling and mRNA processing. Main interactors of PfSET10 included ApiAP2 transcription factors, epigenetic regulators, mediators of RNA polymerase II and DNA replication licensing factors. The combined data pinpoint PfSET10 as a histone H3 lysine K18 methyltransferase regulating DNA and RNA metabolic processes important for intraerythrocytic development of P. falciparum.

ORGANISM(S): Cellular Organisms

SUBMITTER: Gabriele Pradel 

PROVIDER: PXD052931 | JPOST Repository | Tue Sep 24 00:00:00 BST 2024

REPOSITORIES: jPOST

Dataset's files

Source:
Action DRS
20200420_up_5445entries_plasmodium_falicparum_refence_proteome_UP000001450_isolate3D7.fasta Fasta
I220602_22.raw Raw
I220602_23.raw Raw
I220602_24.raw Raw
I220602_25.raw Raw
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