H2B

H2B (PF3D7_1105100) is a canonical core histone of Plasmodium falciparum that packages the parasite genome into nucleosomes and localizes to the parasite nucleus (PMID:9149412, PMID:28033404). Its expression is developmentally regulated: H2B mRNA is undetectable in ring stages and rises through trophozoites and schizonts, with protein levels peaking dramatically in late trophozoite/schizont stages in a pattern consistent with replication-coupled nucleosome assembly (PMID:10579431, PMID:16410041). Nucleosomes incorporating H2B show reduced salt stability relative to human nucleosomes and adopt the shortest known nucleosome repeat length (155 bp), a distinctive feature of parasite chromatin (PMID:28033404). H2B is deposited and handled by histone chaperones — the nucleosome assembly proteins PfNapS/PfNAPS and the nucleoplasmin PfNPM bind assembled H2A/H2B, with PfNPM engagement requiring its acidic tracts, though both chaperones bind H2B with lower affinity than the H3/H4 pair (PMID:15899528, PMID:20377878, PMID:40049416). Canonical H2B carries a post-translational modification profile distinct from that of the H2B.Z variant, and both forms are co-detected with the PfSWR1 remodeling complex whose primary deposition substrate is the H2B.Z variant (PMID:19351122, PMID:38564734). Beyond these chaperone interactions, chromatin properties, and expression profile, no direct functional or knockout phenotype for PF3D7_1105100 has been characterized in the available corpus.

1. 1995 Medium

   Establishing that P. falciparum encodes a canonical H2B histone at all was the necessary first step before any chromatin biology could be studied in the parasite.

   Evidence Gene cloning and sequencing of the P. falciparum H2B gene

   PMID:7637710

   Open questions at the time

   • No functional assay beyond sequence identification
   • Nucleosomal incorporation not shown
2. 1997 Medium

   Purifying the protein and confirming sequence homology and nuclear localization established that the cloned gene produces a bona fide nuclear histone rather than merely an ORF.

   Evidence Protein purification, N-terminal sequencing and immunofluorescence in schizonts

   PMID:9149412

   Open questions at the time

   • Did not test DNA binding directly
   • Nucleosome context not established
3. 1999 Low

   Mapping H2B transcript across the life cycle addressed whether the histone is constitutive or stage-restricted, revealing developmental regulation absent in rings.

   Evidence Northern blot / transcript analysis across developmental stages

   PMID:10579431

   Open questions at the time

   • Single lab, single transcript method with no protein-level confirmation
   • Regulatory mechanism not defined
4. 2004 Medium

   Recombinant expression of the P. vivax ortholog tested whether the histone binds DNA and localizes to the nucleus, and modeling flagged divergence from host H2B at modification and DNA-contact sites.

   Evidence Recombinant expression, South-Western DNA binding, confocal microscopy and structural modeling in P. vivax

   PMID:15276199

   Open questions at the time

   • Shown in P. vivax ortholog, not directly in P. falciparum PF3D7_1105100
   • Functional consequence of divergent residues untested
5. 2006 Medium

   Quantifying protein levels and confirming synthesis by MS resolved whether the stage-restricted transcription translates into protein accumulation, linking H2B expression to late-stage DNA replication.

   Evidence Real-time RT-PCR, immunoblotting and mass spectrometry across stages

   PMID:16410041

   Open questions at the time

   • Correlation with replication is inferential, not causal
   • Chromatin loading kinetics not measured
6. 2009 Medium

   Global MS mapping distinguished canonical H2B from the H2B.Z variant by their post-translational modification patterns, establishing that the two forms are chemically and likely functionally distinct.

   Evidence LC-MS/MS mapping of P. falciparum histone modifications

   PMID:19351122

   Open questions at the time

   • Functional consequence of the distinct modification pattern not tested
   • Enzymes writing/erasing the marks not identified
7. 2010 Medium

   Structural and spectroscopic characterization of PfNapS identified where core histones including H2B are recognized, defining the chaperone-histone interface distinct from the linker H1 site.

   Evidence Crystal structure of PfNapS plus fluorescence spectroscopy interaction mapping

   PMID:20377878

   Open questions at the time

   • H2B was one of several histones tested, not the focus
   • Functional relevance of the interaction in vivo not shown
8. 2016 High

   Reconstitution and mapping showed that H2A/H2B confer reduced salt stability and that parasite nucleosomes have an unusually short repeat length, defining a biophysically distinct chromatin state.

   Evidence In vitro nucleosome reconstitution, salt stability assays and in vivo nucleosome mapping

   PMID:28033404

   Open questions at the time

   • Contribution of PF3D7_1105100 versus H2B.Z to instability not fully partitioned
   • Consequences for gene regulation not established
9. 2024 Low

   Reciprocal pulldowns placed both canonical H2B and H2B.Z with the PfSWR1 remodeler, addressing which chromatin machinery handles the histones while establishing the variant as the primary deposition substrate.

   Evidence Reciprocal co-immunoprecipitation and mass spectrometry

   PMID:38564734

   Open questions at the time

   • Mechanistic role of canonical H2B in the SWR1 complex not established
   • Co-detection may reflect nucleosomal association rather than a functional role
10. 2025 High

    Crystallography, binding assays and mutagenesis defined how the nucleoplasmin PfNPM engages assembled H2A/H2B, showing equimolar acidic-tract-dependent binding that is weaker than for H3/H4 and displaceable by H3/H4.

    Evidence Crystal structure of PfNPM, binding affinity measurements and acidic-tract mutagenesis

    PMID:40049416

    Open questions at the time

    • In vivo role of PfNPM-H2B interaction not demonstrated
    • Whether this hand-off governs nucleosome assembly timing not shown

• Whether PF3D7_1105100 is essential and what phenotype its loss produces remains unaddressed, as no genetic knockout, knockdown, or direct functional perturbation of the canonical H2B has been reported.
• No knockout or conditional depletion
• No defined regulatory function separate from bulk chromatin packaging
• Role of its distinct modifications unresolved