Affinage · Plasmodium

AP2-G

PF3D7_1222600 · AP2 domain transcription factor AP2-G

Annotated
2026-09-08
70 papers in source corpus 24 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PF3D7_1222600 (AP2-G) is the master transcriptional activator that commits asexually replicating P. falciparum to sexual differentiation, and its function is both necessary and sufficient for gametocytogenesis: forward and reverse genetics established it as essential for sexual-stage development (PMID:24572369), the orthologous PbAP2-G is required for commitment in P. berghei (PMID:24572359), and conditional overexpression of AP2-G converts >90% of parasites into gametocytes in both species (PMID:30177743, PMID:32577509). AP2-G acts through its AP2 DNA-binding domain, which recognizes a GnGTAC/GTACNY consensus motif; a single V2163L substitution in this domain abolishes DNA binding, eliminates transcriptional activation, and abrogates autoregulation of the ap2-g locus (PMID:41547993, PMID:18541913). Genome-wide occupancy mapping shows AP2-G dynamically binds hundreds to over a thousand sites, directly activating early gametocyte genes, autoregulating its own locus, and inducing a downstream transcription-factor cascade including AP2-G2 and AP2-FG, with regulation requiring physical interaction with PfAP2-I (PMID:32198457, PMID:34119684, PMID:29094698). Beyond transcriptional reprogramming, AP2-G is also required for stabilization of gametocyte-specific transcripts (PMID:28416533). In asexual parasites the locus is kept silent within HP1-dependent H3K9me3 heterochromatin whose maintenance depends on locus-specific cis-elements and on metabolic S-adenosylmethionine availability (PMID:25121746, PMID:42443261, PMID:37277533); derepression occurs stochastically at baseline (PMID:24572369) or is actively triggered by GDV1-mediated HP1 eviction, which is essential for the initial activation of the silent locus (PMID:29590075, PMID:41547993). After commitment the ap2-g locus is silenced again by H3K36me2/3 in stage II gametocytes (PMID:33794978).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2008 Medium

    Before AP2-G's regulatory role was known, it was unclear which cis motifs Plasmodium ApiAP2 factors recognize; establishing the AP2 domain's binding specificity was the prerequisite for coupling this trans factor to its target promoters.

    Evidence Protein-binding microarrays defining cognate DNA motifs for ApiAP2 domains including that of PF3D7_1222600

    PMID:18541913

    Open questions at the time
    • In vitro binding specificity does not establish in vivo occupancy or function
    • Does not identify the biological process AP2-G controls
  2. 2014 High

    The identity of the master switch for sexual commitment was unknown; forward and reverse genetics in both P. falciparum and P. berghei established AP2-G as the essential, feedback-regulated transcription factor whose ablation abolishes gametocyte production.

    Evidence Loss-of-function mutants, conditional ablation, genome-wide motif mapping and transcriptional profiling (P. falciparum); forward screen plus gene deletion (P. berghei)

    PMID:24572359 PMID:24572369

    Open questions at the time
    • Direct genome-wide binding not yet mapped
    • Mechanism keeping the locus silent in asexual parasites not defined
  3. 2014 High

    Having identified AP2-G, the field needed to explain how it stays off in replicating parasites; HP1-dependent heterochromatin and the histone deacetylase Hda2 were shown to silence the locus and control conversion frequency.

    Evidence Conditional depletion of PfHP1 and PfHda2 with transcriptional profiling and gametocytogenesis assays

    PMID:25121746 PMID:25121747

    Open questions at the time
    • What triggers de-silencing physiologically was not resolved
    • Hda2 evidence is single-lab (Medium)
  4. 2016 Medium

    It was unclear whether ap2-g silencing was absolute; genome sequencing of non-producing lines and epigenetic analysis established that the locus is a stochastically activated, epigenetically labile switch, explaining baseline conversion.

    Evidence Whole-genome sequencing of gametocyte-deficient F12/A4 lines and epigenetic/transcriptional analysis of asexual parasites

    PMID:24572369 PMID:27098483

    Open questions at the time
    • Molecular basis of stochastic activation not defined
    • Loss-of-function mutations distinct from the epigenetic switch mechanism
  5. 2017 High

    Whether AP2-G merely initiates or executes a broader program was open; single-cell RNA-seq and comparative KO transcriptomics showed AP2-G triggers a downstream cascade of other ApiAP2 factors and chromatin modifiers, placing it atop a regulatory network.

    Evidence Single-cell RNA-seq with conditional AP2-G knockdown (P. falciparum); systematic ApiAP2 KO screen and comparative transcriptomics (P. berghei)

    PMID:28081440 PMID:29094698

    Open questions at the time
    • Direct vs indirect targets not distinguished by expression alone
    • Cascade wiring across stages incomplete
  6. 2018 High

    The trigger derepressing ap2-g and the sufficiency of AP2-G were unresolved; GDV1 was shown to evict HP1 to activate the locus, and AP2-G overexpression was shown to be sufficient to drive synchronous gametocyte conversion.

    Evidence Conditional GDV1 overexpression with HP1 ChIP (P. falciparum); inducible AP2-G overexpression achieving >90% conversion (P. berghei); marker tracking revealing two conversion routes (P. falciparum)

    PMID:29590075 PMID:30177743 PMID:30478286

    Open questions at the time
    • How environmental cues feed into GDV1 not fully mapped
    • Two-route conversion evidence is Medium confidence
  7. 2020 High

    The direct genome-wide targets and protein partners of AP2-G were needed to define its mechanism; ChIP-seq identified over a thousand binding sites, autoregulation, and a downstream TF cascade, and co-IP showed AP2-G requires PfAP2-I as a cofactor.

    Evidence ChIP-seq, conditional knockdown, transcriptional profiling and co-immunoprecipitation (P. falciparum); ChIP-seq with expression timing (P. berghei); conditional expression with RNA-seq (P. falciparum)

    PMID:32198457 PMID:32577509 PMID:34119684

    Open questions at the time
    • Structural basis of the AP2-G/PfAP2-I interaction unknown
    • Functional consequence of same-cycle vs next-cycle occupancy differences unresolved
  8. 2021 Medium

    The layers restraining and terminating AP2-G expression were incompletely defined; PfAP2-G5 was identified as a direct repressor, PfAP2-G2 as an indirect upstream regulator, and H3K36me2/3 as a post-commitment silencing mark.

    Evidence ChIP-seq/KO showing PfAP2-G5 direct binding and repression; KO/RT-qPCR/ChIP-qPCR implicating PfAP2-G2; ChIP-seq with Jumonji inhibitor for H3K36 methylation

    PMID:33537025 PMID:33794978 PMID:34365503

    Open questions at the time
    • PfAP2-G2 link to ap2-g is single-method RT-qPCR and Low confidence
    • How post-commitment H3K36 repression is targeted temporally is unknown
  9. 2015 Medium

    Whether AP2-G acts only at transcription was unclear; biosynthetic mRNA labeling in AP2-G-deficient F12 parasites showed the sexual program initiates but aborts, and gametocyte transcript stabilization also fails, revealing a role beyond initial transcription.

    Evidence Thiol-modified pyrimidine biosynthetic labeling comparing wild-type and F12 (AP2-G-deficient) parasites

    PMID:28416533

    Open questions at the time
    • Mechanism linking AP2-G to transcript stabilization not defined
    • Single-lab study
  10. 2022 Medium

    Whether upregulation of the endogenous locus alone drives commitment was untested outside overexpression constructs; CRISPRa activation of the native locus increased AP2-G transcripts and gametocytemia, confirming dosage sufficiency at the endogenous gene.

    Evidence Inducible dCas9-GCN5 CRISPRa targeting the ap2-g locus with RT-qPCR and gametocytemia readout

    PMID:35510853

    Open questions at the time
    • Does not distinguish transcriptional from epigenetic derepression contributions
    • Single-lab study
  11. 2023 High

    How metabolic state biases the epigenetic switch was unknown; SAM competition between histone methyltransferases and phosphoethanolamine methyltransferase was shown to modulate H3K9me3-based ap2-g silencing under phosphatidylcholine-precursor scarcity.

    Evidence Molecular genetics, metabolomics and H3K9me3 ChIP with conditional manipulation of the phospholipid pathway

    PMID:37277533

    Open questions at the time
    • Quantitative link between SAM flux and per-cell conversion probability not established
    • Whether other metabolic cues converge on the same node unknown
  12. 2026 High

    The DNA-binding requirement and the division of labor between GDV1-driven initial activation and AP2-G autoregulation were undefined; a V2163L point mutation that abolishes DNA binding proved AP2-G binding is required for activation and autoregulation, while GDV1 initiates the silent locus in the absence of functional AP2-G.

    Evidence CRISPR forward/reverse point mutagenesis, DNA-binding assays, transcriptional reporters and transgenic AP2-G.L2163 lines

    PMID:40568120 PMID:41547993

    Open questions at the time
    • Structural basis of V2163 in motif recognition not resolved
    • How GDV1 activation and AP2-G autoregulation are quantitatively coupled remains open
  13. 2026 Medium

    Whether locus-specific DNA sequence dictates heterochromatin at ap2-g was unresolved; a URE-G cis-element was shown to be required for high local H3K9me3 without altering global heterochromatin, and distinct locus fragments were shown to serve nucleation versus maintenance roles.

    Evidence Cis-element deletion and heterologous integration assays with H3K9me3 ChIP and gametocyte formation readouts

    PMID:40455742 PMID:42443261

    Open questions at the time
    • Trans factors reading URE-G to recruit methylation not identified
    • Nucleation is low-efficiency and requires large fragments, leaving the primary signal ambiguous

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory inputs — GDV1-triggered HP1 eviction, SAM-dependent methylation, cis-element-based heterochromatin maintenance, repressors PfAP2-G5/AP2-G2, and AP2-G autoregulation — are quantitatively integrated to set the per-cell probability and timing of commitment remains unresolved.
  • No structural model of AP2-G on DNA or with PfAP2-I
  • Mechanism by which AP2-G stabilizes gametocyte-specific transcripts unknown
  • Temporal control of post-commitment H3K36-based silencing not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification
Partners
AP2-FG (DOWNSTREAM CASCADE TARGET) [#10]GDV1 (UPSTREAM ACTIVATOR VIA HP1 EVICTION; REQUIRED FOR INITIAL LOCUS ACTIVATION) [#4, #17]PFAP2-G2 (INDIRECT UPSTREAM REGULATOR; DOWNSTREAM CASCADE TARGET) [#24, #10]PFAP2-G5 (DIRECT TRANSCRIPTIONAL REPRESSOR OF THE AP2-G LOCUS) [#14]PFAP2-I (PHYSICAL INTERACTION REQUIRED FOR AP2-G-DEPENDENT REGULATION) [#6]PFHDA2 (UPSTREAM EPIGENETIC REGULATOR OF AP2-G EXPRESSION) [#3]PFHP1 (HETEROCHROMATIN-BASED SILENCER OF THE LOCUS) [#2]

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 AP2-G (PF3D7_1222600) is a DNA-binding transcription factor that functions as a master regulator of sexual-stage development. Forward and reverse genetics demonstrated that PF3D7_1222600 function is essential for P. falciparum sexual differentiation; genome-wide PF3D7_1222600 cognate motif occurrence combined with global transcriptional changes from PF3D7_1222600 ablation identified early gametocyte genes as direct targets whose wild-type expression depends on PF3D7_1222600. Forward genetics (loss-of-function mutants), reverse genetics (conditional ablation), genome-wide motif mapping, transcriptional profiling Nature High 24572369
2014 PbAP2-G (ortholog of PF3D7_1222600) in P. berghei is essential for commitment of asexually replicating forms to sexual development. Loss-of-function mutations in the gene encoding PbAP2-G (PBANKA_143750) were identified from parasites that had lost the ability to produce sexual stages after blood passage, and systematic gene deletion confirmed its essential role in gametocytogenesis. Data are consistent with a positive feedback loop involving PbAP2-G. Forward genetics (mutation identification from blood-passaged parasites), systematic gene deletion, transcriptional analysis Nature High 24572359
2014 PfHP1 (heterochromatin protein 1) controls expression of PF3D7_1222600 (pfap2-g): conditional depletion of PfHP1 causes derepression of PF3D7_1222600, leading to increased gametocyte conversion, establishing PfHP1-dependent heterochromatin as a silencer of the ap2-g locus. Conditional protein depletion (PfHP1 knockdown), transcriptional profiling, gametocytogenesis assay Cell host & microbe High 25121746
2014 PfHda2 (P. falciparum histone deacetylase 2) globally silences virulence genes and controls the frequency of PF3D7_1222600 (PfAP2-g) expression; depletion of PfHda2 leads to dysregulated PF3D7_1222600 expression and increased gametocytogenesis, identifying PfHda2 as an upstream epigenetic regulator of AP2-G. Conditional gene depletion (PfHda2 knockdown), transcriptional profiling, gametocytogenesis assay Cell host & microbe Medium 25121747
2018 GDV1 (gametocyte development 1 protein) acts as an upstream activator of PF3D7_1222600 (ap2-g) by targeting heterochromatin and triggering HP1 eviction, thereby derepressing the ap2-g locus. GDV1 expression was itself responsive to environmental triggers of sexual conversion and controlled via a gdv1 antisense RNA. Conditional overexpression of GDV1, chromatin immunoprecipitation (HP1 occupancy assay), transcriptional profiling, genetic manipulation Science (New York, N.Y.) High 29590075
2008 The AP2 domain of PF3D7_1222600 (PfAP2-G) binds specific DNA sequences; the DNA-binding specificity of ApiAP2 domains (including the one in PF3D7_1222600) was characterized using protein-binding microarrays, identifying cognate motifs and coupling these trans factors to cis-regulatory motifs in Plasmodium. Protein-DNA sequence specificity is conserved in orthologous proteins between phylogenetically distant Apicomplexan species. Protein-binding microarrays (PBM), computational prediction, comparative genomics Proceedings of the National Academy of Sciences of the United States of America Medium 18541913
2020 PF3D7_1222600 (PfAP2-G) is a transcriptional activator that dynamically binds hundreds of sites across the genome; ChIP-seq identified direct targets including early gametocyte genes and genes important for red blood cell invasion. PF3D7_1222600 occupancy differs between gametocytes derived via next-cycle versus same-cycle conversion. Regulation by PF3D7_1222600 requires physical interaction with PfAP2-I (a second transcription factor). ChIP-seq (genome-wide occupancy), conditional knockdown, transcriptional profiling, co-immunoprecipitation Nature communications High 32198457
2017 Single-cell RNA sequencing of malaria cultures during sexual commitment showed that AP2-G (PF3D7_1222600) expression during the commitment cycle drives transcriptional changes in nascent merozoites; AP2-G+ mature schizonts specifically upregulate additional regulators of gene expression (other AP2 transcription factors, histone-modifying enzymes, and regulators of nucleosome positioning), suggesting AP2-G activates a downstream epigenetic cascade. A conditional AP2-G knockdown line was used to attribute these changes to PF3D7_1222600. Single-cell RNA sequencing, conditional AP2-G knockdown, comparative transcriptomics Nature High 29094698
2018 PF3D7_1222600 (PfAP2-G)-positive sexually committed parasite stages exist prior to the previously known committed schizont stage. Two distinct routes to sexual conversion were demonstrated: (1) PF3D7_1222600-expressing parasites completing a replicative cycle before converting, and (2) a direct route with conversion within the same cycle as initial PF3D7_1222600 expression, linked to early ring-stage expression. This was demonstrated using PF3D7_1222600 as a molecular marker of commitment. Conditional expression system tracking PF3D7_1222600, plaque assays, reanalysis of single-cell RNA-seq data Nature microbiology Medium 30478286
2018 In P. berghei, conditional overexpression of AP2-G (ortholog of PF3D7_1222600) synchronously converts the great majority (>90%) of parasites into fertile gametocytes, demonstrating that AP2-G is sufficient to trigger gametocytogenesis and that gender-specific transcription occurs within 6 hours of induction. Conditional overexpression (inducible AP2-G system), flow cytometry, transcriptomics Nature microbiology High 30177743
2020 PF3D7_1222600 (PfAP2-G) expression in P. berghei begins at ~12 h post-invasion, peaks at ~18 h when sexual features first appear, and decreases as sex-specific features manifest. ChIP-seq at peak expression identified >1,000 genomic binding sites with the main motif GTACNY. Targets include genes related to protein biogenesis and upstream gametocyte-specific transcription factors (AP2-G2, AP2-FG, and AP2-G itself), indicating AP2-G autoregulates and activates a transcriptional cascade for early gametocyte differentiation. Fluorescence microscopy (expression timing), ChIP-seq (genome-wide binding), gene disruption assays Parasitology international Medium 34119684
2020 A conditional PF3D7_1222600 (PfAP2-G) expression system in P. falciparum achieves ~90% sexual conversion upon induction. Transcriptomic and phenotypic characterization of sexually committed schizonts and sexual rings revealed downregulation of genes involved in solute transport upon sexual commitment, among other transcriptional changes attributable to PF3D7_1222600 induction. Conditional expression system (inducible PfAP2-G), RNA-seq, flow cytometry, phenotypic characterization Science advances High 32577509
2017 In P. berghei, the ap2-g gene (ortholog of PF3D7_1222600) was found to have non-essential functions in blood stages, and AP2-G2 was identified as a repressor active in both asexual and sexual stages. Comparative transcriptomics across ApiAP2 mutants and developmental stages established that AP2-G is part of a network of stage-specific interacting ApiAP2 proteins controlling co-regulated gene clusters with shared cis promoter elements. Systematic knockout screen, comparative transcriptomics, cis-element analysis Cell host & microbe Medium 28081440
2015 Transcriptional biosynthetic labeling experiments in F12 parasites (which lack functional PF3D7_1222600/PfAP2-G) showed that the transcriptional program required for sexual commitment and maturation is initiated but aborted in the absence of PF3D7_1222600, and gametocyte-specific mRNA stabilization fails. This establishes that PF3D7_1222600 is required both for transcriptional reprogramming and for stabilization of gametocyte-specific transcripts. Biosynthetic mRNA labeling (thiol-modified pyrimidine incorporation via FCU expression), comparative transcriptomics between wild-type and F12 (PfAP2-G-deficient) parasites Genome research Medium 28416533
2021 PfAP2-G5 (PF3D7_1139300) suppresses transcriptional activity of PF3D7_1222600 (pfap2-g) by binding to its upstream region and gene body, the latter linked to maintenance of local heterochromatin, thereby preventing sexual commitment. Knockout of pfap2-g5 upregulates PF3D7_1222600 expression and promotes sexual commitment, establishing PfAP2-G5 as a direct transcriptional repressor of PF3D7_1222600. Systematic ApiAP2 functional screening, gene knockout, ChIP-seq, RNA-seq Nucleic acids research Medium 34365503
2023 The frequency of PF3D7_1222600 (ap2-g) derepression is regulated by metabolic competition for S-adenosylmethionine (SAM) between histone methyltransferases and phosphoethanolamine methyltransferase. When phosphatidylcholine precursors (LysoPC, choline) are scarce, increased SAM consumption for de novo phosphatidylcholine synthesis impairs histone methylation (H3K9me3) responsible for silencing the ap2-g locus, increasing derepression frequency and sexual differentiation. Molecular genetics, metabolomics, chromatin profiling (H3K9me3 ChIP), conditional manipulation of phospholipid pathway Nature microbiology High 37277533
2021 H3K36me2 and H3K36me3 at the PF3D7_1222600 (ap2-g) locus in stage II gametocytes actively repress the gene post-commitment, providing the first evidence of ap2-g repression in post-commitment gametocytes. This H3K36 methylation-mediated repression is a stage-specific mechanism that operates after the gene's initial activation. Chromatin immunoprecipitation followed by sequencing (ChIP-seq), Jumonji inhibitor treatment (JIB-04), transcriptional profiling Epigenetics & chromatin Medium 33794978
2026 A single valine-to-leucine substitution at position 2163 (V2163L) within the AP2 DNA-binding domain of PF3D7_1222600 (AP2-G) abolishes DNA binding to the consensus motif GnGTAC, eliminates transcriptional activation of target genes, and abrogates autoregulation of the ap2-g locus. Using AP2-G.L2163 parasite lines, GDV1 was shown to be essential for the initial activation of the silent ap2-g locus during the trophozoite-to-schizont transition in the absence of functional AP2-G. AP2-G.V2163 (wild-type) was required for MSRP1 expression, distinguishing early from late sexually committed schizonts. Forward and reverse mutation editing (CRISPR), DNA-binding assays, transcriptional reporter assays, transgenic parasite lines Nature communications High 41547993
2025 A single valine-to-leucine substitution (V2163L) in the AP2 domain of PF3D7_1222600 abrogates DNA binding to the GnGTAC motif and eliminates AP2-G-dependent transcription including autoregulation (preprint version of the published study above). GDV1 was shown to drive initial activation of the silent ap2-g locus in the absence of functional AP2-G, demonstrating GDV1's critical role in the initial trophozoite-to-schizont activation step. Forward and reverse mutation editing, DNA-binding assays, transcriptional reporter assays bioRxiv : the preprint server for biologypreprint Medium 40568120
2026 A cis-regulatory element (URE-G) within the pfap2-g (PF3D7_1222600) locus is required for high levels of H3K9 methylation at the ap2-g locus. Deletion of URE-G decreases H3K9me3 at this locus, resulting in PF3D7_1222600 activation and increased gametocyte formation without altering global heterochromatin structure, establishing a sequence-dependent mechanism for heterochromatin maintenance specifically at the ap2-g locus. Cis-regulatory element deletion (genetic manipulation), H3K9me3 ChIP analysis, gametocyte formation assay Scientific reports Medium 42443261
2025 Fragments from the beginning of the coding sequence of PF3D7_1222600 (pfap2-g) nucleate H3K9me3-marked heterochromatin with low efficiency (requiring long ~2 kb fragments and occurring in only a fraction of parasites), whereas fragments from the pfap2-g upstream region do not nucleate heterochromatin but are required for its maintenance, demonstrating that the primary DNA sequence at different parts of the ap2-g locus plays distinct roles in HC nucleation versus maintenance. Integration of regulatory fragments into euchromatic loci, H3K9me3 ChIP analysis PLoS pathogens Medium 40455742
2016 Genomic sequencing of gametocyte non-producing 3D7-derived lines F12 and A4 confirmed that the PF3D7_1222600 locus (encoding PfAP2-G) harbors mutations responsible for the loss of gametocyte production, validating PF3D7_1222600 as the genetic switch for gametocyte development in these lines. Whole genome sequencing of gametocyte non-producing lines Malaria journal Medium 27098483
2022 A CRISPRa system targeting PF3D7_1222600 (PfAP2-G) achieved >10-fold increase of PfAP2-G transcripts, resulting in >4-fold higher gametocytemia in induced P. falciparum parasites, demonstrating that transcriptional upregulation of PF3D7_1222600 is sufficient to drive increased sexual commitment. Inducible CRISPRi/a (dCas9-GCN5 activation), RT-qPCR, gametocytemia assay Microbiology spectrum Medium 35510853
2016 PF3D7_1222600 (ap2-g) is epigenetically silenced in asexual parasites and is among a set of loci prone to spontaneous stochastic activation; this stochastic activation mechanism provides the baseline rate of gametocyte production observed in culture and infections. Epigenetic analysis, transcriptional profiling of asexual parasites, genetic ablation experiments Nature Medium 24572369
2021 PfAP2-G2 knockout in P. falciparum leads to downregulation of PF3D7_1222600 (PfAP2-G) specifically at the schizont stage (but not ring stage), and ChIP-qPCR showed PfAP2-G2 is enriched at the transcriptional start site of PfMDV-1 in ring and schizont stages, implicating PfAP2-G2 as an indirect upstream regulator of PF3D7_1222600 expression during schizogony. Gene knockout, RT-qPCR, RNA-seq, ChIP-qPCR Frontiers in microbiology Low 33537025

Source papers

Stage 0 corpus · 70 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 A transcriptional switch underlies commitment to sexual development in malaria parasites. Nature 397 24572369
2005 Discovery of the principal specific transcription factors of Apicomplexa and their implication for the evolution of the AP2-integrase DNA binding domains. Nucleic acids research 395 16040597
2014 A cascade of DNA-binding proteins for sexual commitment and development in Plasmodium. Nature 326 24572359
2014 Heterochromatin protein 1 secures survival and transmission of malaria parasites. Cell host & microbe 217 25121746
2018 GDV1 induces sexual commitment of malaria parasites by antagonizing HP1-dependent gene silencing. Science (New York, N.Y.) 195 29590075
2008 Specific DNA-binding by apicomplexan AP2 transcription factors. Proceedings of the National Academy of Sciences of the United States of America 193 18541913
2014 A Plasmodium falciparum histone deacetylase regulates antigenic variation and gametocyte conversion. Cell host & microbe 174 25121747
2017 Single-cell RNA sequencing reveals a signature of sexual commitment in malaria parasites. Nature 168 29094698
2009 Identification of a transcription factor in the mosquito-invasive stage of malaria parasites. Molecular microbiology 164 19220746
2017 A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle. Cell host & microbe 163 28081440
2010 The Apicomplexan AP2 family: integral factors regulating Plasmodium development. Molecular and biochemical parasitology 156 21126543
2018 Chromatin Accessibility-Based Characterization of the Gene Regulatory Network Underlying Plasmodium falciparum Blood-Stage Development. Cell host & microbe 140 29649445
2010 A major role for the Plasmodium falciparum ApiAP2 protein PfSIP2 in chromosome end biology. PLoS pathogens 134 20195509
2009 Transcription factor AP2-Sp and its target genes in malarial sporozoites. Molecular microbiology 129 20025671
2017 Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor. Cell host & microbe 113 28618269
2020 Dissecting the role of PfAP2-G in malaria gametocytogenesis. Nature communications 108 32198457
2018 Regulation of Sexual Commitment and Gametocytogenesis in Malaria Parasites. Annual review of microbiology 91 29975590
2018 Revisiting the initial steps of sexual development in the malaria parasite Plasmodium falciparum. Nature microbiology 91 30478286
2012 Identification of an AP2-family protein that is critical for malaria liver stage development. PloS one 88 23144823
2015 Global transcriptional repression: An initial and essential step for Plasmodium sexual development. Proceedings of the National Academy of Sciences of the United States of America 84 26417110
2012 A tetracycline-repressible transactivator system to study essential genes in malaria parasites. Cell host & microbe 76 23245327
2021 Higher gametocyte production and mosquito infectivity in chronic compared to incident Plasmodium falciparum infections. Nature communications 73 33903595
2020 Conditional expression of PfAP2-G for controlled massive sexual conversion in Plasmodium falciparum. Science advances 67 32577509
2018 Inducible developmental reprogramming redefines commitment to sexual development in the malaria parasite Plasmodium berghei. Nature microbiology 65 30177743
2020 Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential. Genome medicine 63 31915075
2014 Endoplasmic reticulum stress triggers gametocytogenesis in the malaria parasite. The Journal of biological chemistry 63 24755215
2016 Proteome-wide analysis reveals widespread lysine acetylation of major protein complexes in the malaria parasite. Scientific reports 62 26813983
2019 Plasmodium falciparum sexual differentiation in malaria patients is associated with host factors and GDV1-dependent genes. Nature communications 60 31086187
2017 Adaptation of Plasmodium falciparum to its transmission environment. Nature ecology & evolution 59 29255304
2023 Regulators of male and female sexual development are critical for the transmission of a malaria parasite. Cell host & microbe 58 36634679
2021 A cascade of transcriptional repression determines sexual commitment and development in Plasmodium falciparum. Nucleic acids research 49 34365503
2016 Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia. Proceedings of the National Academy of Sciences of the United States of America 48 27911780
2010 The construction and use of log-odds substitution scores for multiple sequence alignment. PLoS computational biology 48 20657661
2020 From Genes to Transcripts, a Tightly Regulated Journey in Plasmodium. Frontiers in cellular and infection microbiology 46 33425787
2015 Specific expression and export of the Plasmodium falciparum Gametocyte EXported Protein-5 marks the gametocyte ring stage. Malaria journal 46 26315106
2023 Sexual differentiation in human malaria parasites is regulated by competition between phospholipid metabolism and histone methylation. Nature microbiology 42 37277533
2020 Artemisinin exposure at the ring or trophozoite stage impacts Plasmodium falciparum sexual conversion differently. eLife 42 33084568
2017 Capturing in vivo RNA transcriptional dynamics from the malaria parasite Plasmodium falciparum. Genome research 40 28416533
2021 Mechanisms of triggering malaria gametocytogenesis by AP2-G. Parasitology international 29 34119684
2023 Plasmodium falciparum adapts its investment into replication versus transmission according to the host environment. eLife 27 36916164
2020 Rrp6 Regulates Heterochromatic Gene Silencing via ncRNA RUF6 Decay in Malaria Parasites. mBio 26 32487761
2023 Characterization of the dual role of Plasmodium falciparum DNA methyltransferase in regulating transcription and translation. Nucleic acids research 25 37026483
2020 Disruption of the Plasmodium falciparum Life Cycle through Transcriptional Reprogramming by Inhibitors of Jumonji Demethylases. ACS infectious diseases 25 32272012
2010 From cradle to grave: RNA biology in malaria parasites. Wiley interdisciplinary reviews. RNA 25 21935891
2021 Single-Cell RNA Sequencing Reveals Cellular Heterogeneity and Stage Transition under Temperature Stress in Synchronized Plasmodium falciparum Cells. Microbiology spectrum 24 34232098
2019 The role of epigenetics and chromatin structure in transcriptional regulation in malaria parasites. Briefings in functional genomics 24 31220857
2017 A disrupted transsulphuration pathway results in accumulation of redox metabolites and induction of gametocytogenesis in malaria. Scientific reports 24 28091526
2022 A Dynamic and Combinatorial Histone Code Drives Malaria Parasite Asexual and Sexual Development. Molecular & cellular proteomics : MCP 23 35051657
2019 A patatin-like phospholipase functions during gametocyte induction in the malaria parasite Plasmodium falciparum. Cellular microbiology 23 31734953
2022 Identification of a novel AP2 transcription factor in zygotes with an essential role in Plasmodium ookinete development. PLoS pathogens 22 35947628
2021 A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite-Induced Controlled Malaria Infection. The Journal of infectious diseases 22 32239171
2019 Predicting gene expression in the human malaria parasite Plasmodium falciparum using histone modification, nucleosome positioning, and 3D localization features. PLoS computational biology 20 31509524
2020 Metabolic regulation of sexual commitment in Plasmodium falciparum. Current opinion in microbiology 17 33053503
2016 Genomic variation in two gametocyte non-producing Plasmodium falciparum clonal lines. Malaria journal 17 27098483
2021 A 39-Amino-Acid C-Terminal Truncation of GDV1 Disrupts Sexual Commitment in Plasmodium falciparum. mSphere 16 34011691
2022 Plasmodium falciparum Sexual Commitment Rate Variation among Clinical Isolates and Diverse Laboratory-Adapted Lines. Microbiology spectrum 15 36409095
2021 H3K36 methylation reprograms gene expression to drive early gametocyte development in Plasmodium falciparum. Epigenetics & chromatin 15 33794978
2022 A Leak-Free Inducible CRISPRi/a System for Gene Functional Studies in Plasmodium falciparum. Microbiology spectrum 14 35510853
2021 PfAP2-G2 Is Associated to Production and Maturation of Gametocytes in Plasmodium falciparum via Regulating the Expression of PfMDV-1. Frontiers in microbiology 14 33537025
2025 Pink or blue: sex determination in malaria gametocytes. Trends in parasitology 2 41107154
2025 Transcription factor 25 modulates gametocytogenesis and ribosome biogenesis in the malaria parasite Plasmodium falciparum. Frontiers in cellular and infection microbiology 2 41210950
2025 Heterochromatin de novo formation and maintenance in Plasmodium falciparum. PLoS pathogens 1 40455742
2026 A single valine to leucine switch disrupts Plasmodium falciparum AP2-G DNA binding and reveals GDV1's role in ap2-g activation. Nature communications 0 41547993
2026 Molecular mechanisms involved in Plasmodium gametocytogenesis. Frontiers in microbiology 0 41716278
2026 A heterologous marker-free selection approach for CRISPR/Cas9-based gene editing in the malaria parasite Plasmodium falciparum. mSphere 0 41885428
2026 A divergent Plasmodium NEK4 acts as a key regulator driving the early events of meiosis. Nature communications 0 42120403
2026 Identification of a sequence element regulating H3K9 methylation at the ap2-g locus in Plasmodium falciparum. Scientific reports 0 42443261
2026 Persistence of Plasmodium falciparum DNA detection after antimalarial treatment and the implication of gametocytes: a prospective cohort study in a non-endemic setting. Microbiology spectrum 0 42684939
2025 A single valine to leucine switch disrupts Plasmodium falciparum AP2-G DNA binding and reveals GDV1's role in ap2-g activation. bioRxiv : the preprint server for biology 0 40568120
2025 A divergent Plasmodium NEK4 acts as a key regulator driving the early events of meiosis. bioRxiv : the preprint server for biology 0 41332573