histone
Enable an AI agent to identify a histone, assess its molecular and assembly state, and choose justified characterization, handling or experimental interventions.
Research draft, second pass
A second pass drafted this model: the structure a model of this thing needs, and what is known about it in the world. The line under this one says how the second half was obtained - researched against sources, or recalled without web access, in which case nothing here was read anywhere and every claim is a lead to verify. Unreviewed either way.
Researched by: Codex + Grok
Purpose and description
Enable an AI agent to identify a histone, assess its molecular and assembly state, and choose justified characterization, handling or experimental interventions.
A histone is a small, highly conserved, positively charged nuclear protein that packages eukaryotic DNA into nucleosomes by wrapping ~147 bp of DNA around an octamer of core histones (two each of H2A, H2B, H3 and H4), with linker histone H1 binding internucleosomal DNA; post-translational modifications of histone tails constitute a major chromatin-regulatory code.
It can be Classify a histone family and variant while retaining unresolved sequence assignments.; Map processing, mutations and modifications onto a defined reference sequence.; Select complementary assays to resolve identity, modification or assembly ambiguity.; Assess whether a histone preparation is suitable for binding, modification or chromatin-reconstitution experiments.; Plan and evaluate histone modification, exchange, assembly or disassembly under documented conditions.; Compare histone populations across conditions without treating association measurements as causal regulatory conclusions..
Distinguishing features
Require sequence or structural evidence supporting histone-family membership; DNA binding or basic charge alone does not distinguish a histone from other DNA-binding proteins.
Distinguish the H2A, H2B, H3 and H4 core-histone families from linker histone H1 rather than requiring all histones to share one assembly role. Reference classification: [NCBI HistoneDB](https://www.ncbi.nlm.nih.gov/research/histonedb/).
For H1 assignments, test family identity and compatibility with association near nucleosomal DNA entry-exit regions rather than imposing a core-histone role. Reference: [NCBI H1 classification](https://www.ncbi.nlm.nih.gov/research/histonedb/type/H1/).
Distinguish a histone protein from a nucleosome by recording whether the referent is a protein constituent or a DNA-protein assembly.
Distinguish sequence variants from modified proteoforms by separately establishing amino-acid sequence and covalent modifications; an antibody label or apparent gel mass alone is insufficient.
Scope
+ Histone family, variant, organism and sequence identity
+ Residue-specific modifications, processing and engineered changes
+ Folding, solubility, aggregation and molecular integrity
+ Association with DNA, other histones and histone chaperones
+ Histone-specific assay interpretation and preparation suitability
+ Evidence supporting classification, state judgments and interventions
- Histone genes, transcription units and RNA processing as independently modeled entities
- Whole nucleosomes, chromatin fibers and chromosomes as assemblies
- DNA sequence identity and genome annotation beyond binding-context references
- Histone-modifying enzymes, chaperones and chromatin remodelers as independent entities
- Cell-wide epigenetic programs, gene regulation and disease diagnosis
- Nonhistone DNA-binding proteins and isolated synthetic histone-tail peptides as complete histones
Characteristics
- Histone family and variant
- H2A, H2B, H3, H4, H1, other supported histone family, unresolved; variant with classification reference Determines which identity criteria, assembly expectations and comparisons apply.
- Sequence and biological origin
- Versioned protein accession or explicit sequence; source organism; encoding locus when distinguishable Anchors identity and prevents unsupported assignment among indistinguishable gene products.
- Material origin
- Endogenous isolate, recombinant, chemically synthesized, semisynthetic, mixed, unknown Changes expectations about native modifications, contaminants and biological interpretation.
- Sequence integrity
- Full length, processed, clipped, degraded, engineered; mapped alterations and confidence Separates intended variants or constructs from damage and incomplete material.
- Residue modification state
- Modification chemistry, residue, numbering convention, localization confidence; unknown and unmodified distinguished Defines the proteoform without conflating absent evidence with absence of modification.
- Modification occupancy
- Fraction or percent of the stated histone population at a specified site; method and uncertainty Distinguishes a minority modified population from a uniformly modified preparation.
- Assembly membership
- Free, histone oligomer, chaperone-bound, nucleosome-associated, linker-associated, other, unresolved; partner identities Determines whether molecular surfaces and proposed manipulations are accessible.
- Physical condition
- Soluble, precipitated, aggregated; folding assessment under recorded solution conditions Separates usable material from preparations whose apparent activity may reflect physical artifacts.
- Histone concentration and purity
- mol/L or mg/mL; purity fraction or percent with analytical basis Supports controlled comparisons and interpretation of binding or assembly experiments.
- Biological or experimental location
- Cell compartment, extracellular material, genomic association or in-vitro preparation; method, time and resolution Constrains interpretation of the histone's observed state and accessibility.
Also called
Where this came from
wikidata · CC0 1.0
Drafted structure
Bundle to layer to finding to question, as the second pass will find it: 6 bundles · 11 layers · 18 findings · 28 questions.
Histone identity Establishes what histone is represented and at what level of specificity.
Family, variant and gene-product ambiguity change how every subsequent observation should be interpreted.
Family and variant
Separates supported histone classification from resemblance or naming convention.
Supported histone assignment
Record the proposed family and variant together with discriminating evidence and unresolved alternatives.
- Which sequence features, structural observations or curated classification support this histone-family assignment? definition
- Can the evidence distinguish the proposed variant from related histones and nonhistone proteins? boundary
Sequence and origin
Anchors the protein to a sequence and a biological or manufactured source.
Traceable histone material
Identify the source organism, reference sequence, preparation origin and any ambiguity among encoding loci.
- Which versioned sequence and source organism define this histone, and can its encoding locus actually be distinguished? provenance
- Was the material isolated from cells, expressed recombinantly or synthesized, and what construct changes were introduced? provenance
Histone proteoform Describes the actual molecular form beyond its family name.
A histone sequence designation does not specify its processing, covalent modifications or population heterogeneity.
Sequence integrity
Distinguishes intact material, deliberate engineering and proteolytic changes.
Mapped sequence alterations
Record observed termini, substitutions, deletions and tags against an explicit residue-numbering convention.
- Which termini and sequence alterations are experimentally established, and how are residue positions mapped to the reference? measurement
- Which alterations were designed, arose biologically or appeared during isolation and storage? provenance
Modification and occupancy
Represents modification identity, localization and abundance without inventing a uniform proteoform.
Resolved modification pattern
Record site-specific evidence and distinguish measured co-occurrence on one molecule from separate population signals.
- Which modifications are localized to which residues, with what confidence and site occupancy? measurement
- Does the assay establish that reported modifications coexist on the same molecule, or only within the same sample? boundary
Histone association Records the histone's partners, assembly role and location.
Free, chaperone-bound and chromatin-associated histones require different state judgments and experimental actions.
Assembly partners
Identifies protein and nucleic-acid associations appropriate to the histone family.
Observed assembly state
Record partners, supported stoichiometry and whether the histone participates in a defined assembly or heterogeneous mixture.
- Is this histone free, oligomerized, chaperone-bound or associated with a DNA-containing assembly, and what evidence distinguishes these states? measurement
- Which partner identities and stoichiometries are measured rather than assumed from a canonical nucleosome model? boundary
Location and exchange
Places association observations in their biological and temporal context.
Contextual histone occupancy
Record compartment, genomic association and exchange observations with the resolution supported by the method.
- Where and when was this histone detected, and does the method resolve individual molecules, loci or only population enrichment? measurement
- What evidence supports stable association, deposition or exchange under the recorded conditions? measurement
Histone measurement validity Determines what analytical results actually establish about the histone.
Closely related sequences, modification-sensitive reagents and pooled measurements can produce misleading identity or state assignments.
Analyte specificity
Tests whether the assay distinguishes the intended family, variant or modification.
Discriminating assay evidence
Record reagent validation, sequence coverage and unresolved cross-reactivity or analytical ambiguity.
- Which controls establish that the antibody, peptide signal or other readout identifies the intended histone or modification? measurement
- Could shared peptides, neighboring modifications, epitope accessibility or unresolved signals explain the observation? boundary
Quantitation and inference
Separates histone abundance, modification fraction and chromatin enrichment.
Bounded state conclusion
Attach units, denominators, uncertainty and inferential limits to each state judgment.
- Does the result measure total histone amount, a modification fraction or relative chromatin enrichment, and what denominator was used? measurement
- What additional evidence is needed before linking this observation to altered chromatin behavior or gene regulation? boundary
Histone use and intervention Connects preparation condition to justified manipulations and outcome checks.
An identified histone may still be unsuitable for an experiment because of aggregation, contamination, proteoform mixtures or incompatible assembly conditions.
Preparation fitness
Assesses whether the available material can support the intended histone experiment.
Usable histone preparation
Record concentration, purity, physical integrity and condition history against the intended use.
- What measurements establish histone concentration, purity, solubility and integrity in the actual working buffer? measurement
- Do nucleic-acid carryover, residual purification reagents, aggregation or storage-related changes compromise the intended assay? action
Controlled histone manipulation
Defines feasible interventions and evidence that the intended molecular or assembly change occurred.
Verified histone state transition
Specify the intended modification, binding, exchange or reconstitution outcome with prerequisites and acceptance criteria.
- Which modification, exchange or assembly action is justified by this histone's identity, accessible sites, partners and preparation condition? action
- Which before-and-after measurements will confirm the intended change and detect unintended proteoform or assembly heterogeneity? action
Evidence and external alignment What the world already says about this thing, gathered so the model can be checked against it.
A model that cannot be lined up against existing standards, identifiers and practice cannot be adopted by anyone who already uses them.
Reported evidence
Findings from the breadth pass, kept separate from the structural claims.
Kinds and varieties
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- H2A (core histone)
- H2B (core histone)
- H3 (core histone)
- H4 (core histone)
- H1 / linker histone
- histone variants (e.g. H2A.Z, H2A.X, H3.3, CENP-A/CenH3, macroH2A)
- histone post-translational modification states (acetylation, methylation, phosphorylation, ubiquitination)
- archaeal histone homologs
- Which of these kinds and varieties hold for the sense of histone this model covers, and on what evidence? provenance
Identifiers and schemes
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Wikidata - Q28823 - Wikidata item for histone (protein family)
- UniProt Keyword - KW-0349 - UniProt keyword Histone
- HGNC gene family - Histones (gene family 864 and related histone gene clusters) - Human histone genes are clustered, mainly at 6p22.1-p22.2 and 1q21
- InterPro / Pfam - IPR007125 / PF00125 (Histone core); PF00538 (linker histone H1/H5)
- ChEBI - CHEBI:15358 - histone (role/class in chemical ontology; use with care vs protein family)
- Which of these identifiers and schemes hold for the sense of histone this model covers, and on what evidence? provenance
Standards and regulation
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- HUPO Proteomics Standards Initiative (PSI-MS / PSI-MOD): controlled vocabularies for histone PTMs in proteomic reporting
- IUPAC / IUBMB biochemical nomenclature: residue numbering and PTM naming for histone modifications
- Human Genome Organisation Gene Nomenclature Committee (HGNC): official human histone gene symbols (HIST1/H1-H4 cluster names and revised H1-/H2-/H3-/H4- symbols)
- Clinical / biosafety: recombinant histone reagents and chromatin assays fall under general laboratory biosafety and IVD/research-use labelling (no histone-specific statute)
- Which of these standards and regulation hold for the sense of histone this model covers, and on what evidence? provenance
Real-world use
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Chromatin immunoprecipitation (ChIP-seq / CUT&RUN / CUT&Tag) using modification-specific histone antibodies to map epigenetic states
- Western blot, ELISA and mass-spectrometry assays of histone PTMs as research and translational biomarkers
- Recombinant histones and nucleosome reconstitution kits for structural biology and enzyme assays (HATs, HDACs, KMTs, KDMs)
- CENP-A / H3.3 / H2A.X variant assays in chromosome-segregation, development and DNA-damage research
- Therapeutic targeting of histone-modifying enzymes (HDAC inhibitors, EZH2 inhibitors, BET bromodomain inhibitors) rather than histones themselves
- Forensic and pathology immunohistochemistry of histone marks (e.g. γH2A.X) as DNA-damage indicators
- Which of these real-world use hold for the sense of histone this model covers, and on what evidence? provenance
Typical measurements
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Nucleosomal DNA wrap length - 145-147 - bp
- Core histone polypeptide length - H3 ~135 aa; H4 ~102 aa; H2A ~129 aa; H2B ~125 aa; H1 ~194-220 aa (human canonical) - amino acids
- Core histone molecular mass - ~11-15 (H4 smallest ~11.2; H3 ~15.3) - kDa
- Linker histone H1 molecular mass - ~21-23 - kDa
- Net charge / pI (core histones) - strongly basic, pI typically ~10-12 - pI (dimensionless)
- Histone:DNA mass ratio in chromatin - approximately 1:1 - mass/mass
- Nucleosome repeat length (species/tissue dependent) - ~160-240 (often ~180-200 in higher eukaryotes) - bp
- Which of these typical measurements hold for the sense of histone this model covers, and on what evidence? provenance
Failure modes and hazards
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Oncogenic histone mutations (e.g. H3 K27M, H3 G34R/V, H3 K36M 'oncohistones') drive specific paediatric and young-adult cancers by poisoning chromatin-modifying complexes
- Mis-assignment of PTM antibodies (lot-to-lot cross-reactivity) yields false epigenetic maps
- Histone extraction artefacts (acid extraction, over-fixation) alter apparent modification occupancy
- Excess free histones in extracellular space after cell death are cytotoxic and pro-inflammatory (damage-associated molecular patterns; contribute to sepsis and thrombosis)
- HDAC/KMT inhibitor toxicity from global chromatin and non-histone substrate effects
- Replication-dependent histone mRNA/protein imbalance causes genome instability
- Which of these failure modes and hazards hold for the sense of histone this model covers, and on what evidence? provenance
Regional variation
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- Gene nomenclature: older HIST1H3A-style cluster names remain in many datasets; HGNC has renamed many to H3C1, H4C1, H2AC4, H1-4 etc., so mapping differs by database vintage and region of use
- Oncohistone diagnostic practice is concentrated in neuropathology centres (diffuse midline glioma H3 K27-altered) under WHO CNS tumour classification, not uniformly applied in all health systems
- Canonical vs variant histone gene repertoires differ across eukaryotes; plants and protists have distinct variant sets and repeat lengths
- Archaea package DNA with histone-fold proteins that form dimers/tetramers rather than octameric nucleosomes; 'histone' as a term is used more loosely in microbiology than in animal chromatin biology
- Which of these regional variation hold for the sense of histone this model covers, and on what evidence? provenance
Neighbouring kinds and how to tell them apart
Reported by the breadth pass; each item needs checking against its source before it becomes normative.
- protamine - Protamines replace histones during spermatogenesis; they are arginine-rich, form toroidal DNA packing, and lack the nucleosome octamer fold of core histones.
- high-mobility group (HMG) proteins - HMGs are non-histone chromatin proteins that bind nucleosomal or linker DNA but are not stoichiometric components of the histone octamer; distinguished by sequence (HMG-box / AT-hook) and extractability.
- histone-fold transcription factors / NC2 / TBP-associated factors - Share the histone-fold dimerization motif but do not package genomic DNA into nucleosomes; distinguished by complex membership (TFIID, SAGA) and lack of nucleosome-core stoichiometry.
- nucleosome / chromatin - The nucleosome is the particle (histone octamer + DNA); chromatin is the fibre; histone is the protein subunit. Distinguish by whether DNA is part of the named entity.
- histone-modifying enzymes (HATs, HDACs, KMTs, KDMs, kinases) - Enzymes that write or erase marks on histones are not histones; they are identified by catalytic domains (GNAT, MYST, JmjC, SET, Zn-dependent deacetylase) and substrates that include non-histone proteins.
- archaeal histone vs eukaryotic core histone - Archaeal histones typically form homodimers that tetramerize and wrap ~60-120 bp without H2A/H2B or H1; eukaryotic nucleosomes are octameric with ~147 bp DNA. Sequence identity of the histone fold plus oligomeric state separates them.
- Which of these neighbouring kinds and how to tell them apart hold for the sense of histone this model covers, and on what evidence? provenance
Sources
- Histone - Nucleosome packaging of eukaryotic DNA by core histones H2A, H2B, H3 and H4 and the role of linker histone H1.
- Histones - Protein-family definition, conservation, and UniProt keyword assignment for histones.
- Crystal structure of the nucleosome core particle - Atomic structure of the histone octamer wrapping DNA in the nucleosome core particle.
What the second pass must settle
- With no registry definition recorded, should this entry explicitly include archaeal histones and viral histone homologs, and what evidence should determine their inclusion?
- Which classification authority and version should govern variant naming and ambiguous assignments across organisms?
- When does a clipped histone or engineered fusion remain an instance of histone rather than require linkage to a separate fragment or construct model?
- What evidence thresholds should support claims of modification co-occurrence, variant-specific occupancy and causal chromatin effects?
- Which preparation acceptance criteria and extracellular-state considerations are required for the intended applications?