ArticleNucleic acids research2022
Genome-wide landscape of ApiAP2 transcription factors reveals a heterochromatin-associated regulatory network during Plasmodium falciparum blood-stage development.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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46 citing papers in PubMed, 85 citations in OpenAlex.
- AP2-HS and a GDV1 regulatory feedback loop mediate environmental induction of sexual conversion in Plasmodium falciparum.Nature microbiology · 2026Article
- The DNA-binding protein PfAP2-V regulates erythrocyte invasion and pathogenesis of the human malaria parasite Plasmodium falciparum.Science China. Life sciences · 2026Article
- A critical role of the histone lysine demethylase JmjC1 in regulating severe malaria-associated virulence genes in Plasmodium falciparum.Nature communications · 2026Article
- Characterisation of the thermal and non-thermal stress conditions that activate the Plasmodium falciparum AP2-HS-dependent heat-shock response.PLoS pathogens · 2026Article
- Global-scale population genetic analysis of Plasmodium falciparum identifies region-specific patterns of malaria parasite adaptation.Nature communications · 2026Article
- Targeting protein-protein interactions in Plasmodium: from asexual replication to sexual development.Parasites & vectors · 2026Review
- PfVPS4, an ESCRT AAA-ATPase, is essential for asexual proliferation and gametocyte sexual conversion in Plasmodium falciparum.Parasites & vectors · 2026Article
- RALP1 is essential for schizont maturation and erythrocyte invasion in Plasmodium falciparum.Parasites & vectors · 2026Article
- Chromatin state dynamics during the Plasmodium falciparum intraerythrocytic development cycle.BMC genomics · 2026Article
- Heat shock protein Gp96 (Grp94) in malaria: functional insights at the host-parasite interface and therapeutic perspectives.Frontiers in cell and developmental biology · 2026Review
- A guide to the apicomplexan cell cycle: endodyogeny and schizogony.Trends in parasitology · 2025Review
- Comparative genomics, integrated with single-cell sequencing and genetic analyses, reveal roles of transcription factor AP2-M2 in asexual replication of Babesia parasite.PLoS pathogens · 2025Article
- An ApiAP2 Family Transcriptional Factor PfAP2-06B Regulates Erythrocyte Invasion Indirectly inPathogens (Basel, Switzerland) · 2025Article
- Circadian Biology in Parasites: Beyond Known Mechanisms.Annual review of microbiology · 2025Review
- β-hydroxybutyrate inhibits Plasmodium falciparum development and confers protection against malaria in mice.Nature metabolism · 2025Article
- Malaria: past, present, and future.Signal transduction and targeted therapy · 2025Review
- Article
- Heterochromatin de novo formation and maintenance in Plasmodium falciparum.PLoS pathogens · 2025Article
- Transcriptome analysis reveals a de novo DNA element that may interact with chromatin-associated proteins in Plasmodium berghei during erythrocytic development.Scientific reports · 2025Article
- Article
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Heterochromatin-associated gene silencing controls multiple physiological processes in malaria parasites, however, little is known concerning the regulatory network and cis-acting sequences involved in the organization of heterochromatin and how they modulate heterochromatic gene expression. Based on systematic profiling of genome-wide occupancy of eighteen Apicomplexan AP2 transcription factors by ChIP-seq analysis, we identify and characterize eight heterochromatin-associated factors (PfAP2-HFs), which exhibit preferential enrichment within heterochromatic regions but with differential coverage profiles. Although these ApiAP2s target euchromatic gene loci via specific DNA motifs, they are likely integral components of heterochromatin independent of DNA motif recognition. Systematic knockout screenings of ApiAP2 factors coupled with RNA-seq transcriptomic profiling revealed three activators and three repressors of heterochromatic gene expression including four PfAP2-HFs. Notably, expression of virulence genes is either completely silenced or significantly reduced upon the depletion of PfAP2-HC. Integrated multi-omics analyses reveal autoregulation and feed-forward loops to be common features of the ApiAP2 regulatory network, in addition to the occurrence of dynamic interplay between local chromatin structure and ApiAP2s in transcriptional control. Collectively, this study provides a valuable resource describing the genome-wide landscape of the ApiAP2 family and insights into functional divergence and cooperation within this family during the blood-stage development of malaria parasites.
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