| 1995 |
The sequence of Plasmodium falciparum histone H3 (PF3D7_0610400) was determined, establishing its identity as a canonical histone H3 in this parasite. |
DNA sequencing / molecular cloning |
Molecular and biochemical parasitology |
Low |
7723778
|
| 2003 |
Plasmodium falciparum histone H3 was cloned and expressed as a recombinant protein; sequence analysis revealed that the apicomplexan H3 proteins harbor novel and rare features compared to other eukaryotes, establishing the existence of at least two H3 variants (H3 and H3.3) in this parasite. |
Molecular cloning, sequence analysis, recombinant protein expression |
DNA sequence : the journal of DNA sequencing and mapping |
Low |
14509838
|
| 2004 |
Recombinant PfGCN5 acetylates histone H3 (PF3D7_0610400) at lysine 8 and lysine 14 in vitro, establishing H3 as a substrate of PfGCN5 with site-specific modification at K8 and K14. |
In vitro HAT assay with recombinant PfGCN5 using free core histones as substrate, substrate-specific antibodies |
Eukaryotic cell |
High |
15075257
|
| 2006 |
Mass spectrometry of P. falciparum histones identified acetylation of lysines and methylation of lysines and arginines in the N-terminus of histone H3 (PF3D7_0610400). Recombinant PfH3 was efficiently acetylated by both recombinant and native PfGCN5 at K9 and K14, confirming H3 as a substrate despite sequence divergence from mammalian H3 N-termini. H3-K9 acetylation increased in late trophozoite and schizont stages during intraerythrocytic development. |
Mass spectrometry of purified histones, in vitro acetyltransferase assay with recombinant PfH3 and PfGCN5, immunoblotting with acetylation-specific antibodies at multiple time points |
Gene |
High |
16410041
|
| 2006 |
Curcumin treatment caused specific hypoacetylation of histone H3 (PF3D7_0610400) at K9 and K14 (but not H4 at K5, K8, K12, K16) in P. falciparum, consistent with inhibition of PfGCN5 HAT activity, as confirmed by in vitro HAT inhibition assays with recombinant PfGCN5. |
In vitro HAT assay with recombinant PfGCN5, nuclear HAT activity assay, acetylation-specific antibodies |
Antimicrobial agents and chemotherapy |
Medium |
17145789
|
| 2007 |
PfGCN5-mediated acetylation of histone H3 (PF3D7_0610400) at K9 (H3K9ac) is enriched at putative promoter regions of active genes in a stage-specific manner during erythrocytic development; H3K9ac and H3K9me3 marks on H3 act antagonistically as epigenetic markers of active and silent genes respectively, genome-wide. |
ChIP-on-chip (chromatin immunoprecipitation with microarray), real-time PCR, treatment with PfGCN5 inhibitor |
Eukaryotic cell |
High |
17449656
|
| 2007 |
Trimethylation and dimethylation of histone H3 lysine 4 (H3K4me3/me2) on PF3D7_0610400 peaks in the 5' upstream region of transcribed var genes and acts as a bookmarking epigenetic mark during the poised state; H3K9me3 acts antagonistically to K4 methylation to establish stable var gene silencing, while H3K9 acetylation competes with H3K9 methylation in the 5' flanking region to repress or activate var gene expression. |
Chromatin immunoprecipitation (ChIP) with modification-specific antibodies, real-time PCR across var gene regions |
Molecular microbiology |
High |
18028313
|
| 2007 |
H3K9me3 on histone H3 (PF3D7_0610400) serves as an epigenetic mark controlling var gene transcription and antigenic variation, constituting a chromatin memory associated with mutually exclusive var gene expression. |
Chromatin immunoprecipitation (ChIP) with H3K9me3-specific antibodies |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
17209011
|
| 2008 |
Anacardic acid inhibits PfGCN5 HAT activity and induces hypoacetylation of histone H3 (PF3D7_0610400) at K9 and K14 (but not H4 at K5, K8, K12, K16), with ChIP-PCR confirming reduced H3K9 acetylation near promoters of downregulated genes, establishing H3K9/K14ac as functionally linked to active gene expression. |
In vitro HAT inhibition assay with recombinant PfGCN5, acetylation-specific antibodies, ChIP and real-time PCR, microarray gene expression |
Eukaryotic cell |
High |
18487348
|
| 2008 |
Methyl marks were detected on K4, K9, and K36 of histone H3 (PF3D7_0610400) by site-specific methyl-lysine antibodies; two P. falciparum SET-domain protein domains expressed in a eukaryotic system showed histone methyltransferase activity towards H3 in vitro. |
Site-specific methyl-lysine antibodies, in vitro eukaryotic expression and HKMT activity assay |
International journal for parasitology |
Medium |
18299133
|
| 2009 |
The chromodomain (CD) of PfHP1 binds specifically to di- and tri-methylated lysine 9 of histone H3 (PF3D7_0610400) but not to unmodified H3 or H3K4-methylated forms, establishing H3K9me2/3 as the recognition mark for PfHP1-mediated heterochromatin formation and var gene silencing. |
Recombinant protein binding assay (CD of PfHP1 vs. modified/unmodified H3 peptides), ChIP analysis |
Nucleic acids research |
High |
19270070
|
| 2009 |
Mass spectrometry analysis of P. falciparum asexual stage histones revealed a general preponderance of H3/H4 acetylation and H3K4me3 on histone H3. ChIP-on-chip profiling showed H3K4me3 and H3K9ac on H3 are broadly distributed across euchromatic genome regions in asynchronous parasites, with stage-specific patterns: in rings they are homogeneous across genes, while in schizonts they are enriched at the 5' end of active genes. |
Mass spectrometry, ChIP-on-chip with H3, H3K4me3, H3K9me3, H3K9ac antibodies, synchronized parasite analysis |
Proceedings of the National Academy of Sciences of the United States of America |
High |
19497874
|
| 2010 |
H3K9ac and H3K4me3 modifications on histone H3 (PF3D7_0610400) are preferentially deposited at H2A.Z-containing nucleosomes in euchromatic intergenic regions; H3K9ac at promoter regions correlates with transcriptional status dynamically throughout the intraerythrocytic cycle, while H3K4me3 shows stage-specific regulation peaking at trophozoite stage. |
Genome-wide ChIP with next-generation sequencing (ChIP-seq) for H2A.Z, H3K9ac, H3K4me3; RNA-seq at 8 time points; linear amplification library preparation |
PLoS pathogens |
High |
21187892
|
| 2012 |
Recombinant P. falciparum histone H3 (PfH3/PF3D7_0610400) directly stimulated production of IL-8 and other inflammatory mediators by primary human endothelial cells via Src family kinases and p38 MAPK signaling, and induced endothelial permeability through a charge-dependent mechanism; these effects were abrogated by histone-specific antibodies and by recombinant human activated protein C, which proteolytically cleaved PfH3. |
Recombinant PfH3 treatment of primary human dermal microvascular endothelial cells, antibody blocking, kinase inhibitors, live cell imaging, activated protein C cleavage assay |
The American journal of pathology |
High |
22260922
|
| 2013 |
PfSETvs-dependent trimethylation of histone H3 lysine 36 (H3K36me3) on PF3D7_0610400, present along the entire var gene body including the transcription start site, is required for silencing of var genes; knockout of PfSETvs abolished H3K36me3 at var genes and resulted in transcription of virtually all var genes simultaneously. |
PfSETvs knockout by targeted disruption, ChIP with H3K36me3-specific antibodies, RNA-seq, flow cytometry, immunofluorescence |
Nature |
High |
23823717
|
| 2013 |
Fourteen phosphorylation sites on histone H3 (PF3D7_0610400) and other histones were detected by LC-MS/MS in P. falciparum asexual blood stages; Pf14-3-3I was identified as a phospho-H3 reader that preferentially binds H3S28ph over H3S10ph, independent of modification of neighboring residues. |
LC-MS/MS with phosphopeptide enrichment, recombinant Pf14-3-3I protein binding to purified parasite histones, ITC with H3 phosphopeptides, in silico structural analysis |
PloS one |
High |
23308157
|
| 2013 |
Genome-wide ChIP-on-chip mapping of twelve histone modifications including H3K9ac, H3K14ac, H3K56ac, H3K4me3, and H3K79me3 on histone H3 (PF3D7_0610400) throughout the P. falciparum IDC showed dynamic stage-specific enrichment; H3 acetylations correlate with transcript levels and show differential affinity to genomic regions. H4K8ac occupies predominantly promoter regions while H3 marks occur at 5' ends of coding sequences, with promoter occupancy of H4K8ac retained when ectopically inserted at a different locus. |
ChIP-on-chip with modification-specific antibodies across erythrocytic stages, ectopic locus insertion |
PLoS pathogens |
High |
23468622
|
| 2015 |
PfBDP1 bromodomain protein binds to acetylated histone H3 (PF3D7_0610400) at transcriptional start sites of invasion-related genes; conditional PfBDP1 knockdown reduces expression of invasion genes and impairs parasite invasion. |
Conditional knockdown (DiCre or similar), ChIP-seq, co-immunoprecipitation, RNA-seq |
Cell host & microbe |
High |
26067602
|
| 2016 |
PfSET7 is an AdoMet-dependent histone methyltransferase that methylates histone H3 (PF3D7_0610400) at K4 and K9 (with highest activity towards these residues); PfSET7 displays specific substrate preference towards nucleosomes with pre-existing H3K14 acetylation. |
Recombinant PfSET7 expression and purification, in vitro methyltransferase assay with H3 substrates, steady-state kinetics, substrate preference assay with H3K14ac-containing nucleosomes |
Scientific reports |
High |
26902486
|
| 2016 |
A crystal structure of the PfGCN5 bromodomain in complex with the PCAF bromodomain inhibitor L-45 was solved, rationalizing selective binding to PCAF/GCN5 bromodomains; PfGCN5 bromodomain interaction with histone H3.3 (a variant) was disrupted in cells by L-45, but this experiment was performed with H3.3 (the variant), not canonical H3 (PF3D7_0610400). |
Co-crystal structure of PfGCN5-BRD with inhibitor, nanoBRET assay in cells |
Angewandte Chemie (International ed. in English) |
Low |
27966810
|
| 2019 |
Proteolytic clipping of the N-terminal tail of nucleosome-associated histone H3 (PF3D7_0610400) at amino acid position 21 occurs in P. falciparum via a cathepsin C-like activity present in nuclear parasite extracts; ectopically expressed clipped H3 (PfH3p-HA) is targeted to the nucleus, integrates into mononucleosomes, and ChIP-seq shows it is highly enriched upstream of six DNA replication/repair genes, demarcating a specific 1.5 kb chromatin island. |
Nuclear extract proteolytic clipping assay, ectopic expression of truncated H3-HA, ChIP-seq, subcellular fractionation/localization |
EMBO reports |
High |
30833341
|
| 2020 |
H3K18ac and H3K27ac modifications on histone H3 (PF3D7_0610400) dynamically mark regulatory sequences upstream of genes during the asexual life cycle, co-localizing with PfAP2-I, PfBDP1, and PfH2A.Z at stably positioned nucleosomes within exposed DNA at active transcriptional start sites; transient transfection assays showed that sequences enriched for these marks possess promoter activity in schizont stages but no enhancer-like activity. |
ChIP-seq for H3K18ac, H3K27ac, H3K4me1, H3K27ac; integration with existing datasets; transient transfection promoter activity assays |
Epigenetics & chromatin |
High |
33225957
|
| 2021 |
Plasmodium falciparum histone chaperone PfAsf1 specifically interacts with histone H3 (PF3D7_0610400) and H4 and deposits the H3/H4 dimer onto DNA to form disomes; critical residues of PfAsf1 involved in H3/H4 interaction were mapped by site-directed mutagenesis, and the crystal structure of PfAsf1 N-terminal domain was solved at 2.4 Å. |
X-ray crystallography of PfAsf1 (2.4 Å), co-immunoprecipitation/pulldown of PfAsf1 with P. falciparum H3/H4, in vitro nucleosome assembly (disome formation) assay, site-directed mutagenesis of PfAsf1 |
The Biochemical journal |
High |
33501928
|
| 2022 |
The PfBDP1 bromodomain preferentially recognizes tetra-acetylated histone H4 and also weakly interacts with multi-acetylated H2A.Z in addition to previously reported acetylated histone H3 (PF3D7_0610400); a crystal structure of PfBDP1-BRD reveals a unique binding mechanism distinct from human bromodomain families. |
Crystal structure of PfBDP1 bromodomain, solution NMR spectroscopy, ITC binding assays with acetylated histone peptides |
International journal of biological macromolecules |
Medium |
36328269
|
| 2023 |
PfPRMT5 catalyzes symmetric dimethylation of histone H3 (PF3D7_0610400) at R2 (H3R2me2s) and R8 in vitro; genome-wide H3R2me2s marks invasion-related genes and other loci, and PfPRMT5 disruption depletes H3R2me2s and reduces invasion efficiency and invasion gene transcription. |
In vitro methyltransferase assay with recombinant PfPRMT5, ChIP-seq for H3R2me2s, conditional disruption of PfPRMT5, transcriptomics, interactome (Co-IP/MS) |
Communications biology |
High |
37349497
|