Histone H1.4 is a replication-dependent nuclear linker histone encoded in the chromosome 6p22.2 histone cluster. It binds nucleosomal DNA and contributes to chromatin organization across compacted and transcriptionally active states. Post-translational modifications tune its chromatin association and regulatory contacts. Heterozygous C-terminal frameshift variants cause Rahman syndrome, a neurodevelopmental disorder in which overgrowth is variable.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | IEA GO_REF:0000117 | ACCEPT | Summary: Chromatin occupancy spans multiple states. Reason: H1.4 occupies euchromatic and heterochromatic chromatin. This broad unextended location represents both positive pools and the core structural function. |
| GO:0000786 nucleosome | IEA GO_REF:0000002 | ACCEPT | Summary: nucleosome. Reason: Retain H1.4 as an associated nucleosome protein, distinct from the core histone octamer. Supporting Evidence: |
| GO:0000791 euchromatin | IBA GO_REF:0000033 | ACCEPT | Summary: euchromatin. Reason: Retain the euchromatin activity inferred at Theria AN101; the target descends from this experimentally grounded node. Supporting Evidence: file:human/H1-4/H1-4-source-evidence.json |
| GO:0000792 heterochromatin | IDA PMID:15911621 H1 family histones in the nucleus. Control of binding and lo... | ACCEPT | Summary: Heterochromatin localization supported. Reason: Human H1.4 GFP fusions preferentially occupy heterochromatin in mouse fibroblasts; the indexed original supports localization without implying euchromatin exclusion. |
| GO:0000792 heterochromatin | IDA PMID:40240600 Histone H1 deamidation facilitates chromatin relaxation for ... | ACCEPT | Summary: Active heterochromatin context retained. Reason: Retain the curator-assigned activity context; the repair study did not isolate heterochromatin. Separate H1.4 localization supports compatibility, not direct verification of this activity relation. Supporting Evidence: PMID:15911621 differences in their preference for euchromatin and heterochromatin. file:human/H1-4/H1-4-source-evidence.json |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | TOO GENERAL | Summary: DNA binding. Reason: Accepted nucleosomal DNA binding is an is_a descendant of DNA binding in the same enables context. Supporting Evidence: file:human/H1-4/H1-4-source-evidence.json |
| GO:0003690 double-stranded DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: double-stranded DNA binding. Reason: Retain inherited double-stranded DNA binding; nucleosomal DNA binding is not its descendant in the current ontology. Supporting Evidence: file:human/H1-4/H1-4-source-evidence.json |
| GO:0003723 RNA binding | HDA PMID:22681889 The mRNA-bound proteome and its global occupancy profile on ... | UNDECIDED | Reason: The human mRNA interactome assay is described in the authentic abstract, but the H1.4 target entry and peptide assignment remain unverified. Preserve the positive curator assertion without inferring an RNA-binding mechanism from an inaccessible supplement. |
| GO:0005515 protein binding | IPI PMID:17474147 Systematic identification of SH3 domain-mediated human prote... | KEEP AS NON CORE | Reason: Retain non-core NCK1-domain binding to H1.4 peptides. Peptide-array evidence does not establish a broader signaling role or a more specific molecular function. |
| GO:0005515 protein binding | IPI PMID:17540172 L3MBTL1, a histone-methylation-dependent chromatin lock. | KEEP AS NON CORE | Reason: Retain L3MBTL1 association and methylated-H1b recognition as non-core binding; no more specific H1.4 molecular function is established. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Reason: Retain FTSJ3-associated recovery of H1.4 as non-core binding. AP-MS supports co-complex association, not purified pairwise affinity. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | KEEP AS NON CORE | Reason: Retain the nuclear H1.4–RPL14 contact as non-core binding. Cross-linking supports proximity without establishing a more specific molecular function. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | KEEP AS NON CORE | Reason: Retain the nuclear H1.4–H2BC21 contact as non-core binding. Cross-linking supports proximity without establishing a more specific molecular function. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | KEEP AS NON CORE | Reason: Retain the nuclear H1.4–FTSJ3 contact as non-core binding. Cross-linking supports proximity without establishing a more specific molecular function. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | KEEP AS NON CORE | Reason: Retain the nuclear H1.4–SYNGAP1 contact as non-core binding. Cross-linking supports proximity without establishing a more specific molecular function. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | KEEP AS NON CORE | Reason: Retain the nuclear H1.4–UTP3 contact as non-core binding. Cross-linking supports proximity without establishing a more specific molecular function. |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | KEEP AS NON CORE | Reason: Retain the nuclear H1.4–BAZ1B contact as non-core binding. Cross-linking supports proximity without establishing a more specific molecular function. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Reason: Retain RPL14-associated H1.4 recovery as non-core binding with its nuclear context. BioPlex AP-MS does not establish purified pairwise affinity. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Reason: Retain FTSJ3-associated H1.4 recovery as non-core binding with its nuclear context. BioPlex AP-MS does not establish purified pairwise affinity. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Reason: Retain UTP3-associated H1.4 recovery as non-core binding with its nuclear context. BioPlex AP-MS does not establish purified pairwise affinity. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Reason: Retain BAZ1B-associated H1.4 recovery as non-core binding with its nuclear context. BioPlex AP-MS does not establish purified pairwise affinity. |
| GO:0005515 protein binding | IPI PMID:34232536 Interactomes of SARS-CoV-2 and human coronaviruses reveal ho... | KEEP AS NON CORE | Reason: Retain H1.4–nucleocapsid association from tandem affinity purification as non-core binding; no specific host molecular activity is established. |
| GO:0005515 protein binding | IPI PMID:34901782 SARS-CoV-2 nucleocapsid protein binds host mRNAs and attenua... | KEEP AS NON CORE | Reason: Retain H1.4–nucleocapsid association from HEK293 affinity purification as non-core binding, without inferring direct binary affinity. |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | UNDECIDED | Reason: The curated OpenCell H2BC21 association remains unresolved: neither the target table nor an exact current IntAct record was recovered. This access gap does not refute binding. |
| GO:0005515 protein binding | IPI PMID:36217030 A comprehensive SARS-CoV-2-human protein-protein interactome... | KEEP AS NON CORE | Reason: Retain the validated H1.4–nucleocapsid co-immunoprecipitation as non-core binding; a viral regulatory role remains hypothetical. |
| GO:0005515 protein binding | IPI PMID:36950384 Protein interaction studies in human induced neurons indicat... | UNDECIDED | Reason: The curated neuronal SYNGAP1 association remains unresolved because its target-specific IP-MS result was not independently recovered. This access gap does not refute binding. |
| GO:0005634 nucleus | EXP PMID:38530350 Imaging analysis of six human histone H1 variants reveals un... | ACCEPT | Summary: Nuclear localization supported. Reason: Endogenous H1.4 is distributed throughout nuclei in human cell lines; specific phosphorylated pools and antibody cross-reactivity should not define the entire protein's localization. |
| GO:0005634 nucleus | EXP PMID:40240600 Histone H1 deamidation facilitates chromatin relaxation for ... | ACCEPT | Summary: Nuclear localization supported. Reason: Human H1.4 nuclear and chromatin assays support this broad compartment; retain it separately from activity-specific heterochromatin annotation. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: nucleus. Reason: Retain inherited nuclear activity, including valid target experimental self-donor grounding; a narrower location does not replace this activity relation. Supporting Evidence: file:human/H1-4/H1-4-source-evidence.json |
| GO:0005634 nucleus | IDA PMID:17540172 L3MBTL1, a histone-methylation-dependent chromatin lock. | ACCEPT | Summary: Nuclear localization retained. Reason: Retain the curator's nuclear localization. The full localization assay was unavailable for independent inspection. H1b is an established H1.4 name. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: nucleus. Reason: Retain nuclear localization across chromatin states; this located_in assertion is distinct from inferred nuclear activity. Supporting Evidence: UniProtKB:P10412 |
| GO:0005694 chromosome | EXP PMID:15911621 H1 family histones in the nucleus. Control of binding and lo... | TOO GENERAL | Summary: Positive localization retained. Reason: Fusion-protein localization remains supported. Heterochromatin is a narrower location. |
| GO:0005694 chromosome | EXP PMID:21852232 Protein kinase A-mediated serine 35 phosphorylation dissocia... | TOO GENERAL | Summary: Positive localization retained. Reason: Mitotic experiments retain chromatin-associated H1.4 while its phosphorylated S35 pool dissociates. Heterochromatin supplies the narrower unextended location. |
| GO:0005694 chromosome | EXP PMID:38530350 Imaging analysis of six human histone H1 variants reveals un... | TOO GENERAL | Summary: Positive localization retained. Reason: Human H1.4 occupancy remains positive. Prefer the retained heterochromatin location. |
| GO:0005694 chromosome | EXP PMID:40240600 Histone H1 deamidation facilitates chromatin relaxation for ... | TOO GENERAL | Summary: Positive localization retained. Reason: Chromatin association remains supported. Prefer the retained heterochromatin location. |
| GO:0005694 chromosome | IEA GO_REF:0000044 | TOO GENERAL | Summary: chromosome. Reason: Positive heterochromatin localization entails this broader chromosome location through chromatin; the original compartment inference remains positive. Supporting Evidence: file:human/H1-4/H1-4-source-evidence.json |
| GO:0006334 nucleosome assembly | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Later nucleosome incorporation retained. Reason: The GO nucleosome includes associated proteins; assembly is not restricted to forming the core octamer. Retain later H1.4 incorporation as non-core, without inferring histone deposition or chaperone activity. Supporting Evidence: |
| GO:0016607 nuclear speck | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nonexclusive nuclear-speck localization retained. Reason: HPA CAB011506 supports a nuclear-speck pool in A-431, U-251 MG and U2OS. Broad nuclear H1.4 imaging does not exclude that pool; neither observation establishes a speck-specific function. |
| GO:0030261 chromosome condensation | IBA GO_REF:0000033 | ACCEPT | Summary: chromosome condensation. Reason: Retain inherited chromosome condensation; the target’s experimental annotations legitimately contribute to the ancestral evidence. Supporting Evidence: file:human/H1-4/H1-4-source-evidence.json |
| GO:0030261 chromosome condensation | IDA PMID:33238161 Distinct Structures and Dynamics of Chromatosomes with Diffe... | ACCEPT | Summary: Condensation assignment retained. Reason: The source establishes DNA organization in reconstituted chromatosomes. Independent H1.4-dependent mitotic compaction experiments support the cellular role. |
| GO:0030261 chromosome condensation | IDA PMID:35581345 Histone H1 binding to nucleosome arrays depends on linker DN... | ACCEPT | Summary: Condensation assignment retained. Reason: Retain the condensation assignment, grounded here in H1.4-dependent array architecture rather than observed cell division. Independent mitotic experiments support the cellular role. |
| GO:0030261 chromosome condensation | IDA PMID:40240600 Histone H1 deamidation facilitates chromatin relaxation for ... | ACCEPT | Summary: Condensation assignment retained. Reason: Retain the curated condensation assignment; repair-associated compaction does not establish mitotic timing. Independent H89-induced mitotic compaction depended on H1.4, supporting the process. Supporting Evidence: PMID:21852232 the above effect was lost upon H1.4 depletion file:human/H1-4/H1-4-source-evidence.json |
| GO:0030527 structural constituent of chromatin | IDA PMID:33238161 Distinct Structures and Dynamics of Chromatosomes with Diffe... | ACCEPT | Summary: Structural activity supported. Reason: Reconstituted human H1.4 chromatosomes show direct DNA contacts and structural organization. The retained condensation extension describes the inferred cellular role; this assay itself is reconstituted. |
| GO:0030527 structural constituent of chromatin | IDA PMID:35581345 Histone H1 binding to nucleosome arrays depends on linker DN... | ACCEPT | Summary: Structural activity supported. Reason: Full-length human P10412 contacts dyad and linker DNA in reconstituted arrays. Retain structural activity and the condensation context without presenting the array assay as mitosis. |
| GO:0030527 structural constituent of chromatin | IDA PMID:40240600 Histone H1 deamidation facilitates chromatin relaxation for ... | ACCEPT | Summary: Structural activity supported. Reason: Retain the curated structural activity and joint condensation/heterochromatin context; repair assays support compaction. Independent reconstitution establishes DNA contacts, without directly verifying the complete conjunction. Supporting Evidence: file:human/H1-4/H1-4-source-evidence.json PMID:35581345 H1 shows three DNA contacts |
| GO:0030527 structural constituent of chromatin | IEA GO_REF:0000120 | ACCEPT | Summary: structural constituent of chromatin. Reason: Retain structural chromatin activity: human H1.4 contacts DNA and alters chromatin compaction. Supporting Evidence: |
| GO:0031490 chromatin DNA binding | IEA GO_REF:0000117 | TOO GENERAL | Summary: chromatin DNA binding. Reason: Accepted nucleosomal DNA binding entails this broader chromatin DNA binding in the same enables context. Supporting Evidence: file:human/H1-4/H1-4-source-evidence.json |
| GO:0031490 chromatin DNA binding | IMP PMID:15911621 H1 family histones in the nucleus. Control of binding and lo... | TOO GENERAL | Summary: Positive DNA binding retained. Reason: Positive binding is retained; nucleosomal DNA binding provides the narrower enables annotation. |
| GO:0031492 nucleosomal DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: nucleosomal DNA binding. Reason: Retain nucleosomal DNA binding inherited from AN0, supported by actual descendant experiments. Supporting Evidence: file:human/H1-4/H1-4-source-evidence.json |
| GO:0042826 histone deacetylase binding | IPI PMID:15469825 Human SirT1 interacts with histone H1 and promotes formation... | KEEP AS NON CORE | Reason: Retain the specific SIRT1 interaction, supported by the original abstract and curated H1.4 Lys-26 deacetylation. This enzyme–substrate contact is contextual to chromatin regulation; detailed original methods remain unavailable. |
| GO:0045910 negative regulation of DNA recombination | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: negative regulation of DNA recombination. Reason: Retain the experimentally grounded ancestral recombination-restraint inference as non-core; this does not assert a direct human assay. Supporting Evidence: file:human/H1-4/H1-4-source-evidence.json |
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Download this section (compressed HTML)Q: Does the InterPro assembly mapping include H1.4 incorporation into a preassembled nucleosome?
Q: Which endogenous chromatin changes distinguish Rahman C-terminal frameshifts from loss of normal H1.4?
Experiment: Compare isogenic human neurons carrying a disease frameshift, H1-4 knockout and repaired control using matched chromatin accessibility and transcription measurements.
Hypothesis: Rahman frameshifts alter chromatin differently from H1-4 loss.
Type: Isogenic genotype comparison
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