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Showing H1-10H1FX is a alias.

H1-10

Histone H1.10 · UniProt Q92522

Length
213 aa
Mass
22.5 kDa
Annotated
2026-06-10
16 papers in source corpus 10 papers cited in narrative 10 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

H1-10 (H1X) is a replication-independent linker histone variant that partitions into specific genomic compartments to shape chromatin structure and gene regulation (PMID:16006241, PMID:25645921). Unlike replication-dependent H1 subtypes, its abundance is stable through S phase, and it shuttles into nucleolar chromatin during G1 phase (PMID:17868027), with nucleolar enrichment coupled to active rDNA transcription (PMID:38530350). Genome-wide profiling places H1X in high-GC, RNA polymerase II-enriched coding regions and hypomethylated CpG islands, biased toward exons and the 3' ends of expressed genes, where its depletion dysregulates genes linked to cell movement and transport (PMID:25645921). H1X preferentially occupies high-GC A-compartment regions and recently incorporated transposable elements, and its loss derepresses SVA and SINE-Alu elements, establishing a direct role in transposon silencing (PMID:38261975); it likewise contributes to locus-specific repression, occupying the Nanog regulatory region during retinoic acid-induced differentiation (PMID:20974140). Deposition of H1X onto chromatin is governed by the histone chaperone TAF-Iβ, which binds the H1X globular domain through electrostatic contacts in a 2:2 complex that occludes its DNA-binding sites (PMID:35870650). H1X transcription is directly activated by MEF2D downstream of IL-13/IL13RA1 signaling, driving β-CATENIN upregulation and gastric cancer metastasis (PMID:38609001).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2005 Medium

    Established H1X as a distinct linker histone variant by showing it associates with MNase-resistant chromatin like H1.0 yet, unlike H1.0, is not induced by growth arrest or differentiation.

    Evidence Cell fractionation, MNase digestion, and mRNA analysis

    PMID:16006241

    Open questions at the time
    • Did not define genomic targets or chromatin compartments occupied
    • Regulatory function not tested
  2. 2007 Medium

    Revealed cell-cycle-dependent subnuclear dynamics, showing H1X accumulates in nucleolar chromatin during G1 while remaining stable in abundance through S phase, distinguishing it from replication-coupled H1.

    Evidence Immunocytochemistry with cell synchronization across cell-cycle stages

    PMID:17868027

    Open questions at the time
    • Mechanism driving G1 nucleolar relocalization unknown
    • Functional consequence of nucleolar accumulation not established
  3. 2010 Medium

    Linked H1X to locus-specific gene repression by showing it is incorporated into the Nanog regulatory region as the gene is silenced during differentiation.

    Evidence ChIP-qPCR and Western blot in retinoic acid-differentiated NT2 cells

    PMID:20974140

    Open questions at the time
    • Causal repressive role inferred from occupancy correlation, not direct perturbation
    • Recruitment mechanism to Nanog locus unknown
  4. 2015 High

    Defined the genome-wide distribution of H1X, placing it in RNA Pol II-enriched coding regions and hypomethylated CpG islands and tying its depletion to a defined transcriptional phenotype.

    Evidence ChIP-Seq, cell fractionation, and inducible knockdown with expression profiling in breast cancer cells

    PMID:25645921

    Open questions at the time
    • Did not identify how H1X is targeted to these regions
    • Direct vs indirect effects on dysregulated genes not resolved
  5. 2019 Medium

    Provided structural insight into the H1X N-terminal domain, showing it adopts transient alpha-helical structure under DNA-mimicking high ionic strength.

    Evidence Solution NMR backbone resonance assignment and chemical shift analysis

    PMID:30868366

    Open questions at the time
    • Functional role of induced helicity inferred, not directly tested on DNA
    • No full-length structure in chromatin context
  6. 2022 High

    Defined the molecular mechanism of H1X chaperoning, showing TAF-Iβ binds the globular domain electrostatically in a 2:2 complex that occludes DNA-binding sites to prevent premature chromatin deposition.

    Evidence Methyl-TROSY NMR with spin labels, binding assays, structure-guided mutagenesis, and structural modeling

    PMID:35870650

    Open questions at the time
    • How TAF-Iβ hands off H1X for deposition not resolved
    • Cellular regulation of the chaperone interaction not established
  7. 2024 High

    Demonstrated a direct genome-protective function, showing H1X occupancy at recently incorporated transposable elements is required to keep SVA and Alu elements repressed.

    Evidence ChIP-Seq and H1X depletion with transposable element expression analysis across cell lines

    PMID:38261975

    Open questions at the time
    • How H1X distinguishes recent TEs from older ones unknown
    • Cofactors mediating TE silencing not identified
  8. 2024 Medium

    Confirmed and extended H1X subnuclear localization, linking its nucleolar enrichment specifically to active rDNA transcription in a variant-distinct manner.

    Evidence Super-resolution microscopy and rDNA transcription inhibition across multiple human cell lines

    PMID:38530350

    Open questions at the time
    • Functional role of H1X at rDNA not defined
    • Mechanism coupling H1X to rDNA transcription state unknown
  9. 2024 Medium

    Identified an upstream regulatory and disease axis, showing MEF2D directly activates H1X transcription downstream of IL-13/IL13RA1 to promote β-CATENIN and gastric cancer metastasis.

    Evidence ChIP, promoter-binding assays, overexpression/knockdown, proteomics, and mouse metastasis models

    PMID:38609001

    Open questions at the time
    • How elevated H1X mechanistically drives β-CATENIN upregulation not resolved
    • Chromatin targets mediating the metastatic program not mapped
  10. 2024 Medium

    Tested whether elevated H1X is causally sufficient for stress-related behavioral adaptation, finding hippocampal overexpression alone produces no behavioral phenotype.

    Evidence Viral vector overexpression in mouse ventral hippocampus with chronic social defeat stress and behavioral testing

    PMID:38834575

    Open questions at the time
    • Negative result does not exclude a context-dependent or partner-dependent role
    • Did not assess chromatin or transcriptional changes from overexpression

Open questions

Synthesis pass · forward-looking unresolved questions
  • How H1X is specifically targeted to high-GC A-compartment regions, recent transposable elements, and nucleoli, and how its deposition is regulated in vivo beyond TAF-Iβ, remain unresolved.
  • Targeting determinants for compartment-specific deposition unknown
  • Post-translational modifications and their regulatory roles uncharacterized
  • Downstream effectors of H1X-mediated repression not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0005198 structural molecule activity 2 GO:0003677 DNA binding 1
Localization
GO:0005694 chromosome 3 GO:0005634 nucleus 2 GO:0005730 nucleolus 2
Pathway
R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3
Complex memberships
TAF-Iβ–H1X 2:2 complex

Evidence

Reading pass · 10 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 H1X (H1x) localizes to the nucleus and is partially associated with nucleosomes; it is predominantly found in chromatin regions resistant to micrococcal nuclease digestion, resembling the distribution of the replacement histone H1.0. Its gene is solitarily located and produces polyadenylated mRNA, but unlike H1.0, its expression is not induced by growth arrest or differentiation. Cell fractionation, micrococcal nuclease digestion, mRNA analysis (biochemical characterization) Biological chemistry Medium 16006241
2007 H1X undergoes a cell-cycle-dependent change in nuclear distribution: it accumulates in the nucleolus (specifically in condensed nucleolar chromatin) during G1 phase and is evenly distributed throughout the nucleus during S and G2 phases. The amount of H1X protein remains nearly unchanged during S phase, in contrast to replication-dependent H1 subtypes. Immunocytochemistry, cell synchronization, cell-cycle staging Biology of the cell Medium 17868027
2010 During retinoic acid-induced differentiation of NT2 embryonal carcinoma cells, H1X is preferentially incorporated into the regulatory region of the Nanog gene (a stemness marker that is repressed upon differentiation), suggesting a repressive role for H1X at this locus. Chromatin immunoprecipitation (ChIP) coupled with real-time PCR, Western blot FEBS letters Medium 20974140
2015 ChIP-sequencing and cell fractionation in human breast cancer cells revealed that H1X is associated with coding regions, RNA polymerase II-enriched regions, and hypomethylated CpG islands; it accumulates within constitutive or included exons and retained introns and toward the 3' end of expressed genes. H1X knockdown dysregulates a subset of genes related to cell movement and transport; up-regulated genes in H1X-depleted cells have lower-than-average H1 content and do not form an H1 valley upon induction. ChIP-sequencing, cell fractionation, inducible knockdown, gene expression analysis The Journal of biological chemistry High 25645921
2019 NMR backbone resonance assignments of the H1X N-terminal domain and globular domain show that the N-terminal domain adopts transient alpha-helical secondary structural elements at high ionic strength (in the presence of sodium perchlorate), suggesting the N-terminal domain can assume structured conformations in conditions mimicking the presence of DNA. Solution NMR (backbone resonance assignment, chemical shift analysis) Biomolecular NMR assignments Medium 30868366
2022 The histone chaperone TAF-Iβ recognizes H1.10 (H1X) in a 2:2 complex; the TAF-Iβ core interacts mainly through electrostatic interactions with the globular domain of H1.10. Structure-guided mutagenesis confirmed these interactions. The structural model shows that TAF-Iβ occludes the DNA-binding sites of H1.10, providing the mechanism by which TAF-Iβ functions as a chaperone by preventing H1.10 from directly binding DNA. Methyl-TROSY NMR with spin labels, biochemical binding assays, mutagenesis, structural modeling, comparison with chromatosome structure Journal of molecular biology High 35870650
2024 ChIP-Seq profiling in a breast cancer cell line shows H1X preferentially localizes in high-GC regions (A compartment) and is enriched at recently incorporated transposable elements (SVA and SINE-Alu families). H1X depletion leads to derepression of these transposable elements, demonstrating a direct role for H1X in maintaining TE repression. ChIP-Seq, H1X knockdown/depletion, transposable element expression analysis Nucleic acids research High 38261975
2024 Super-resolution imaging and imaging analysis in multiple human cell lines show that H1X is distributed throughout the nucleus and is universally enriched in high-GC regions and in nucleoli. H1X (but not other H1 variants) shows a distinct response to inhibition of ribosomal DNA transcription, linking its nucleolar enrichment to active rDNA transcription. H1 variant depletion affects chromatin structure in a variant-specific manner. Super-resolution microscopy, immunofluorescence, rDNA transcription inhibition, multiple cell lines eLife Medium 38530350
2024 MEF2D transcription factor directly binds the H1X promoter and drives transcriptional activation of H1X in gastric cancer cells. H1X upregulation in turn promotes in vivo metastasis of gastric cancer cells and upregulates β-CATENIN. The IL-13/IL13RA1 signaling axis induces MEF2D and H1X expression in a time-dependent manner. Chromatin immunoprecipitation (ChIP), promoter-binding assay, overexpression/knockdown, proteomics, mouse metastasis models, quantitative RT-PCR Cancer letters Medium 38609001
2024 Overexpression of H1X in the mouse ventral hippocampus via viral vector does not produce behavioral changes (social, anxiety-like, or memory tests) in susceptible, resilient, or unstressed mice, indicating that elevated H1X alone is not sufficient to drive behavioral adaptations to chronic social stress. Viral vector overexpression in vivo, chronic social defeat stress paradigm, behavioral testing Translational psychiatry Medium 38834575

Source papers

Stage 0 corpus · 16 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2015 Genome distribution of replication-independent histone H1 variants shows H1.0 associated with nucleolar domains and H1X associated with RNA polymerase II-enriched regions. The Journal of biological chemistry 58 25645921
2005 Characterisation of human histone H1x. Biological chemistry 53 16006241
2007 G1 phase-dependent nucleolar accumulation of human histone H1x. Biology of the cell 37 17868027
2008 Histone H1x is highly expressed in human neuroendocrine cells and tumours. BMC cancer 24 19108733
2020 A newly identified lncRNA H1FX-AS1 targets DACT1 to inhibit cervical cancer via sponging miR-324-3p. Cancer cell international 15 32760225
2010 Evidence for a dynamic role of the linker histone variant H1x during retinoic acid-induced differentiation of NT2 cells. FEBS letters 13 20974140
2024 MEF2D facilitates liver metastasis of gastric cancer cells through directly inducing H1X under IL-13 stimulation. Cancer letters 9 38609001
2017 Temporally and Spatially Regulated Expression of the Linker Histone H1fx During Mouse Development. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 7 28766996
2024 Genomic profiling of six human somatic histone H1 variants denotes that H1X accumulates at recently incorporated transposable elements. Nucleic acids research 5 38261975
2024 Imaging analysis of six human histone H1 variants reveals universal enrichment of H1.2, H1.3, and H1.5 at the nuclear periphery and nucleolar H1X presence. eLife 5 38530350
2022 Structural Mechanism of TAF-Iβ Chaperone Function on Linker Histone H1.10. Journal of molecular biology 2 35870650
2019 NMR assignments of human linker histone H1x N-terminal domain and globular domain in the presence and absence of perchlorate. Biomolecular NMR assignments 2 30868366
2026 H1FX as a novel biomarker linking pan-apoptosis to immune dysregulation in allergic rhinitis. European journal of medical research 0 41620781
2024 Histone H1x in mouse ventral hippocampus associates with, but does not cause behavioral adaptations to stress. Translational psychiatry 0 38834575
2023 Histone H1x in mouse ventral hippocampus correlates with, but does not cause behavioral adaptations to stress. bioRxiv : the preprint server for biology 0 37986938
2020 Raw nuclear magnetic resonance data of human linker histone H1x, lacking the C-terminal domain (NGH1x), and trajectory data of nanosecond molecular dynamics simulations of GH1x- and NGH1x-chromatosomes. Data in brief 0 32642505

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