ArticleNature microbiology2023
Sexual differentiation in human malaria parasites is regulated by competition between phospholipid metabolism and histone methylation.
Article in Nature microbiology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- AP2-HS and a GDV1 regulatory feedback loop mediate environmental induction of sexual conversion in Plasmodium falciparum.Nature microbiology · 2026Article
- Histone H2B monoubiquitination drives sexual commitment in malaria parasites.Nature microbiology · 2026Article
- Article
- Elevated Plasmodium falciparum sexual conversion in HbAC and HbAS red blood cells in naturally infected malaria patients.PLoS pathogens · 2026Article
- TgSEC14-LTP1 is a vacuole-secreted SEC14/CRAL-TRIO-like protein required for host DAG flux and PC homeostasis in T. gondii.Cell reports · 2026Article
- Mechanistic insights into coordinated var transcriptional switching in malaria parasites.The EMBO journal · 2026Article
- Long-term feeder cell-free cat intestinal organoid cultures to study Toxoplasma gondii's sexual development.Communications biology · 2026Article
- The inducible gametocyte producer (iGP1) strain is well-suited to produce both immature and mature gametocytes for subsequent drug sensitivity profiling.Frontiers in cellular and infection microbiology · 2026Article
- Histone lactylation: A new epigenetic mark in the malaria parasite Plasmodium.PLoS genetics · 2025Article
- Key Regulators of Parasite Biology Viewed Through a Post-Translational Modification Repertoire.Proteomics · 2025Review
- CUT&Tag and DiBioCUT&Tag enable investigation of the AT-rich epigenome of Plasmodium falciparum from low-input samples.Cell reports methods · 2025Article
- Systemic analyses show that the biosynthesis and spatial distribution of fatty acids, triglycerides and lipids differed in male and female mice and humans.Open biology · 2025Article
- Gametocyte production and transmission fitness of African and AsianAntimicrobial agents and chemotherapy · 2025Article
- scRNA-seq reveals transcriptional plasticity of var gene expression in Plasmodium falciparum for host immune avoidance.Nature microbiology · 2025Article
- Variable surface antigen expression, virulence, and persistent infection byMicrobiology and molecular biology reviews : MMBR · 2025Review
- Gametocyte production and transmission fitness of African and AsianbioRxiv : the preprint server for biology · 2025Article
- Unraveling the complexities of ApiAP2 regulation in Plasmodium falciparum.Trends in parasitology · 2024Review
- Single-cell analyses of polyclonal Plasmodium vivax infections and their consequences on parasite transmission.Nature communications · 2024Article
- Comparative genome-wide identification and characterization of SET domain-containing and JmjC domain-containing proteins in piroplasms.BMC genomics · 2024Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
For Plasmodium falciparum, the most widespread and virulent malaria parasite that infects humans, persistence depends on continuous asexual replication in red blood cells, while transmission to their mosquito vector requires asexual blood-stage parasites to differentiate into non-replicating gametocytes. This decision is controlled by stochastic derepression of a heterochromatin-silenced locus encoding AP2-G, the master transcription factor of sexual differentiation. The frequency of ap2-g derepression was shown to be responsive to extracellular phospholipid precursors but the mechanism linking these metabolites to epigenetic regulation of ap2-g was unknown. Through a combination of molecular genetics, metabolomics and chromatin profiling, we show that this response is mediated by metabolic competition for the methyl donor S-adenosylmethionine between histone methyltransferases and phosphoethanolamine methyltransferase, a critical enzyme in the parasite's pathway for de novo phosphatidylcholine synthesis. When phosphatidylcholine precursors are scarce, increased consumption of SAM for de novo phosphatidylcholine synthesis impairs maintenance of the histone methylation responsible for silencing ap2-g, increasing the frequency of derepression and sexual differentiation. This provides a key mechanistic link that explains how LysoPC and choline availability can alter the chromatin status of the ap2-g locus controlling sexual differentiation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.