Affinage

ASF1B

Histone chaperone ASF1B · UniProt Q9NVP2

Length
202 aa
Mass
22.4 kDa
Annotated
2026-06-09
26 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASF1B is a histone H3-H4 chaperone with a specific, non-redundant role in cell proliferation and chromatin assembly during DNA replication (PMID:21179005, PMID:27753532). Its activity depends on intact histone-binding capacity—the V94R binding-deficient mutant fails to drive proliferation—and on histone H3.3 in particular, which synergizes with ASF1B and is required for its proliferative effect (PMID:27753532). Genome-wide, ASF1B occupies the majority of H3.3 nucleosomes and determines H3.3 enrichment at promoters and enhancers, working with the chromatin remodeler BRG1 and H3K27ac to control lineage gene programs; its loss de-represses developmentally silenced genes (PMID:42100853). ASF1B is functionally coupled to replication machinery via HCF-1, with which it co-localizes at replication foci, and its depletion impairs DNA replication (PMID:20133788). Diverging from the paralog ASF1A, ASF1B carries distinct N- and C-terminal determinants that specify preferential chaperone interactions (PMID:23645555), and it is selectively required to sustain proliferation, such that loss triggers S-phase arrest and Chk1/Chk2 checkpoint activation (PMID:21179005, PMID:35599471). ASF1B chaperone function is held in check by CDAN1, which assembles cytosolic complexes that sequester ASF1B through two B-domains and histone-H3-mimicking helices [PMID:bio_10.1101_2024.08.08.607204]. In proliferative and oncogenic contexts ASF1B is transcriptionally induced by FOXM1 and feeds forward to regulate downstream effectors such as PRDX3 (PMID:38537775), stabilizes CDK9 (PMID:32848135), and recruits chromatin modifiers including the lactyltransferase p300 to promote H3K18 lactylation (PMID:42193960). In vivo, ASF1B is required for normal meiotic entry and gonad development and for pre-implantation embryo proliferation (PMID:26850882, PMID:34906203).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 2010 High

    Established that ASF1B, distinct from ASF1A, is specifically required for cell proliferation, defining its core biological role rather than treating the two paralogs as interchangeable.

    Evidence siRNA depletion, cell-cycle exit assays, and transcriptional profiling in cultured cells

    PMID:21179005

    Open questions at the time
    • Molecular basis of the ASF1B-specific requirement not resolved
    • Did not define genome-wide chromatin targets
  2. 2010 High

    Linked ASF1B to active DNA replication by showing it acts downstream of HCF-1 at replication foci, connecting the chaperone to the replication machinery.

    Evidence Co-IP, immunofluorescence co-localization, and siRNA depletion with viral DNA quantification in HSV infection

    PMID:20133788

    Open questions at the time
    • Demonstrated in a viral replication context; relevance to cellular replication inferred
    • Mechanism of chromatin reorganization downstream of HCF-1 not detailed
  3. 2013 Medium

    Explained why ASF1A and ASF1B are non-redundant by mapping divergent N- and C-terminal regions outside the core interface that specify distinct chaperone partnerships.

    Evidence Biochemical binding assays, structural analysis, and evolutionary/positive-selection analysis

    PMID:23645555

    Open questions at the time
    • ASF1B-specific reconstitution and mutagenesis details limited
    • Functional consequences of preferential interactions not tested in cells
  4. 2016 High

    Defined the molecular requirement for ASF1B proliferative function as histone binding and specifically H3.3, not H3.1/H3.2.

    Evidence Overexpression, V94R binding-deficient mutant, H3.3 knockdown, and multiple proliferation readouts in human beta-cells

    PMID:27753532

    Open questions at the time
    • Downstream chromatin events of ASF1B-H3.3 deposition not mapped
    • Restricted to beta-cell model
  5. 2016 Medium

    Demonstrated an in vivo developmental role, showing ASF1B is required for normal meiotic entry timing and gonad development.

    Evidence Asf1b gene-trap knockout mouse with beta-gal reporter, histology, and reproductive phenotyping

    PMID:26850882

    Open questions at the time
    • Molecular mechanism downstream of ASF1B loss in germ cells not resolved
    • Chromatin targets in meiosis not identified
  6. 2021 Medium

    Separated ASF1A and ASF1B roles in early embryogenesis, attributing proliferation maintenance (PCNA accumulation) to ASF1B and paternal H3.3 assembly to ASF1A.

    Evidence Morpholino knockdown with immunofluorescence for PCNA, H3.3, and H3K56ac in mouse embryos

    PMID:34906203

    Open questions at the time
    • Single-lab morpholino approach
    • Direct mechanism linking ASF1B to PCNA accumulation not defined
  7. 2020 Medium

    Identified CDK9 as an ASF1B partner that ASF1B stabilizes, extending ASF1B function into cell-cycle/transcriptional kinase regulation in cancer.

    Evidence Co-IP, Western blot, siRNA knockdown, and xenograft model in cervical cancer cells

    PMID:32848135 PMID:35087760

    Open questions at the time
    • Biochemical mechanism of CDK9 stabilization not dissected
    • Whether stabilization requires histone-chaperone activity unknown
  8. 2022 Low

    Placed ASF1B upstream of the replication checkpoint, showing its loss causes S-phase arrest and Chk1/Chk2 activation.

    Evidence siRNA knockdown, flow cytometry cell-cycle analysis, and Chk1/Chk2 phospho-Western in pancreatic cancer cells

    PMID:35599471

    Open questions at the time
    • No epistasis or reconstitution to establish directness
    • Single-lab observational link
  9. 2024 Medium

    Defined an upstream transcriptional driver, showing FOXM1 directly activates ASF1B which then regulates PRDX3, embedding ASF1B in a proliferation/oxidative-stress axis.

    Evidence ChIP, FOXM1 inhibitor (thiostrepton), knockdown/overexpression, and in vitro/in vivo gastric cancer models

    PMID:38537775

    Open questions at the time
    • Mechanism by which ASF1B controls PRDX3 transcription unclear
    • Whether axis is gastric-cancer-specific not addressed
  10. 2024 High

    Provided a structural mechanism for ASF1B inhibition, showing CDAN1/CDIN1 sequester ASF1B via B-domains and histone-H3-mimicking helices.

    Evidence Single-particle cryo-EM and biochemical reconstitution of CDAN1-ASF1 complexes (preprint)

    PMID:bio_10.1101_2024.08.08.607204

    Open questions at the time
    • Cellular consequences of CDAN1 sequestration on ASF1B function not quantified
    • Preprint, not peer-reviewed
  11. 2026 High

    Delivered the genome-wide chaperone model, mapping ASF1B to most H3.3 nucleosomes and showing it controls H3.3 enrichment, BRG1 recruitment, and lineage gene repression in erythropoiesis.

    Evidence ChIP-seq, ATAC-seq, transcriptome sequencing, BRG1 Co-IP, and ASF1B knockout in mouse fetal liver erythroid cells

    PMID:42100853

    Open questions at the time
    • How ASF1B selects H3.3 sites genome-wide not defined
    • Extent of ASF1A compensation across loci incomplete
  12. 2026 Medium

    Extended ASF1B to chromatin-modifier recruitment, showing it brings p300 to chromatin to promote H3K18 lactylation in HCC.

    Evidence Co-IP, ChIP-seq, Cut&Run, and dual-luciferase reporter in hepatocellular carcinoma cells

    PMID:42193960

    Open questions at the time
    • Mechanism of ASF1B-p300 recruitment not characterized
    • Direct vs indirect H3K18la control unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ASF1B achieves H3.3-selective, locus-specific deposition and integrates its chaperone activity with its many reported cancer signaling partners remains unresolved.
  • No unified model linking histone-chaperone function to CDK9/HOXB3/p300 effects
  • Determinants of ASF1B target-site specificity unknown
  • Whether oncogenic functions require intact histone binding largely untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 2 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 1
Pathway
R-HSA-1640170 Cell Cycle 2 R-HSA-4839726 Chromatin organization 2 R-HSA-69306 DNA Replication 2
Complex memberships
CDAN1-CDIN1-ASF1 cytosolic complex

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 ASF1B expression is proliferation-dependent: both mRNA and protein decrease upon cell cycle exit in cultured cells. Depletion of ASF1B severely compromises proliferation and leads to aberrant nuclear structures, indicating a specific requirement for ASF1B (not ASF1a) in cell proliferation. siRNA depletion, cell cycle exit experiments, Western blot, immunofluorescence, transcriptional profiling The EMBO journal High 21179005
2010 HCF-1 directly and simultaneously interacts with both HSV DNA replication proteins and ASF1B. ASF1B co-localizes with HCF-1 at viral replication foci late in HSV infection, and depletion of ASF1B results in significantly reduced viral DNA accumulation, indicating ASF1B functions in viral DNA replication via chromatin reorganization downstream of HCF-1 recruitment. Co-immunoprecipitation, co-localization (immunofluorescence), siRNA depletion with viral DNA quantification Proceedings of the National Academy of Sciences of the United States of America High 20133788
2013 ASF1a and ASF1b, which arose by gene duplication at the ancestor of jawed vertebrates, have distinct preferential interactions with different H3-H4 chaperones; regions outside the primary interaction surface (in the N- and C-terminal regions) are key determinants of these preferential interactions, as demonstrated by biochemical and structural analyses. Biochemical binding assays, structural analysis, evolutionary/comparative genomics, positive selection analysis Molecular biology and evolution Medium 23645555
2016 ASF1B promotes human β-cell proliferation in a histone-binding-dependent manner; the histone-binding-deficient mutant V94R fails to induce proliferation. Co-expression of histone H3.3 (but not H3.1 or H3.2) synergistically augments ASF1B-mediated β-cell proliferation, and suppression of endogenous H3.3 attenuates the stimulatory effect of ASF1B, establishing that ASF1B requires histone H3.3 binding for its proliferative function. Overexpression, dominant-negative (V94R) mutant, siRNA knockdown of H3.3, multiple proliferation assays (BrdU, Ki67, mitotic markers) Cell cycle (Georgetown, Tex.) High 27753532
2016 Loss of ASF1B in mice reduces female reproductive capacity; ASF1B is specifically expressed in germ cells with peak expression correlating with meiosis, and Asf1b-null female mice show altered timing of meiotic entry and defective gonad development, indicating ASF1B plays a role in chromatin modifications at meiotic entry. Asf1b gene-trap knockout mouse, β-galactosidase reporter assay, histological analysis, reproductive phenotyping Reproduction (Cambridge, England) Medium 26850882
2020 ASF1B forms stable complexes with CDK9 and positively regulates CDK9 stabilization in cervical cancer cells; ASF1B knockdown reduces CDK9 protein levels. Co-immunoprecipitation, Western blot, siRNA knockdown, in vivo tumor xenograft model Cell death & disease Medium 32848135
2021 Asf1a, but not Asf1b, is required for histone H3.3 assembly in the paternal pronucleus after fertilization. Knockdown of Asf1b (but not Asf1a) nearly eliminates nuclear accumulation of PCNA in morula-stage embryos, indicating ASF1B specifically safeguards pre-implantation embryo development by regulating cell proliferation, while Asf1a regulates H3K56ac levels and Oct4 expression. Morpholino-mediated knockdown, immunofluorescence with specific antibodies, confocal microscopy in mouse embryos Epigenetics & chromatin Medium 34906203
2022 ASF1B knockdown in HCC cells reduces expression of PCNA, cyclinB1, cyclinE2, and CDK9, and ASF1B interacts with CDK9 in HCC cells, consistent with a role for ASF1B-CDK9 complex in cell cycle regulation. Co-immunoprecipitation, Western blot, siRNA knockdown Frontiers in oncology Low 35087760
2022 ASF1B knockdown increases S-phase cell cycle arrest and activates checkpoint kinases Chk1 and Chk2, indicating ASF1B normally suppresses replication checkpoint activation in pancreatic cancer cells. siRNA knockdown, flow cytometry cell cycle analysis, Western blot for Chk1/Chk2 phosphorylation Cancer biomarkers : section A of Disease markers Low 35599471
2023 ASF1B interacts with and occupies the TLK1 gene locus (ChIP assay), and the interaction between ASF1B and TLK1 promotes proliferation, cell cycle progression, and metastasis of low-grade glioma cells; overexpression of TLK1 rescues the effects of ASF1B interference. ChIP assay, co-expression rescue experiments, siRNA knockdown, cell functional assays Annals of medicine Low 36947060
2024 Transcription factor FOXM1 directly binds the ASF1B promoter region and regulates ASF1B transcription. In turn, ASF1B regulates PRDX3 transcription in a FOXM1-dependent manner, forming a FOXM1-ASF1B-PRDX3 axis that controls GC cell proliferation and oxidative stress balance. ChIP assay, FOXM1 inhibitor (thiostrepton) treatment, knockdown/overexpression experiments, in vitro and in vivo tumor models Cancer letters Medium 38537775
2024 CDAN1 dimerizes and assembles into cytosolic complexes with CDIN1 and multiple copies of ASF1A/B. Cryo-EM structures reveal that CDAN1 engages ASF1B via two B-domains (found in other ASF1-binding partners) and two helices that mimic histone H3 binding. CDAN1 can recruit two ASF1 molecules simultaneously and sequesters/inhibits ASF1 chaperone function; ASF1A and ASF1B have different requirements for CDAN1 engagement. Single-particle cryo-EM, biochemical reconstitution, structural analysis bioRxiv (preprint)preprint High bio_10.1101_2024.08.08.607204
2025 ASF1B promotes gastric cancer progression by downregulating histone H2AC20, which activates the PI3K/AKT and ERK1/2 signaling pathways; identified by IP-MS and TMT proteomics to define the ASF1B-interacting protein network. Immunoprecipitation-Mass Spectrometry (IP-MS), TMT proteomics, ASF1B knockout/overexpression, in vitro and in vivo tumor models, organoids Frontiers in pharmacology Medium 40041497
2026 ASF1B recruits the transcription factor HOXB3, promoting ZDHHC9 transcription. ZDHHC9 then palmitoylates PCBP1 at residue C109, inhibiting PCBP1 ubiquitination and suppressing SLC7A11-mediated ferroptosis, thus promoting gastric cancer liver metastasis. Identified by immunoprecipitation and LC-MS analyses. Immunoprecipitation/LC-MS, transcriptome sequencing, label-free proteomics, spleen-injection liver metastasis model, IHC, immunofluorescence NPJ precision oncology Medium 41535416
2026 ASF1B occupies >70% of H3.3 nucleosomes in mouse fetal liver erythroid cells and determines H3.3 enrichment at erythroid gene promoters and enhancers. ASF1B predominantly regulates H3.3-encoding genes and erythroid genes (with ASF1A serving a compensatory function). Loss of ASF1B de-represses embryonic/fetal globin genes by altering H3.3 enrichment, erythroid transcription factor binding, and chromatin accessibility. The regulatory pathway involves recruitment of chromatin remodeler BRG1 and accumulation of H3K27ac at active chromatin. ChIP-seq, ATAC-seq, ASF1B knockout in mouse fetal liver cells, transcriptome sequencing, co-immunoprecipitation for BRG1 interaction Nucleic acids research High 42100853
2026 ASF1B recruits the lactyltransferase p300, thereby promoting histone H3K18 lactylation (H3K18la) in hepatocellular carcinoma cells, forming a positive feedback loop with H3K18la. Co-immunoprecipitation, ChIP sequencing, Cut&Run, dual-luciferase reporter assay Cells Medium 42193960

Source papers

Stage 0 corpus · 26 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2010 Asf1b, the necessary Asf1 isoform for proliferation, is predictive of outcome in breast cancer. The EMBO journal 139 21179005
2010 Transcriptional coactivator HCF-1 couples the histone chaperone Asf1b to HSV-1 DNA replication components. Proceedings of the National Academy of Sciences of the United States of America 57 20133788
2020 ASF1B promotes cervical cancer progression through stabilization of CDK9. Cell death & disease 55 32848135
2013 Subfunctionalization via adaptive evolution influenced by genomic context: the case of histone chaperones ASF1a and ASF1b. Molecular biology and evolution 55 23645555
2016 Histone chaperone ASF1B promotes human β-cell proliferation via recruitment of histone H3.3. Cell cycle (Georgetown, Tex.) 39 27753532
2022 ASF1B Serves as a Potential Therapeutic Target by Influencing Cell Cycle and Proliferation in Hepatocellular Carcinoma. Frontiers in oncology 28 35087760
2016 Loss of the histone chaperone ASF1B reduces female reproductive capacity in mice. Reproduction (Cambridge, England) 28 26850882
2021 ASF1B Promotes Oncogenesis in Lung Adenocarcinoma and Other Cancer Types. Frontiers in oncology 27 34568067
2020 LINC00665 Promotes the Progression of Multiple Myeloma by Adsorbing miR-214-3p and Positively Regulating the Expression of PSMD10 and ASF1B. OncoTargets and therapy 16 32764956
2024 Activation of the FOXM1/ASF1B/PRDX3 axis confers hyperproliferative and antioxidative stress reactivity to gastric cancer. Cancer letters 12 38537775
2022 ASF1B enhances migration and invasion of lung cancers cell via regulating the P53-mediated epithelial-mesenchymal transformation (EMT) signaling pathway. Neoplasma 10 35103478
2022 Downregulation of ASF1B inhibits tumor progression and enhances efficacy of cisplatin in pancreatic cancer. Cancer biomarkers : section A of Disease markers 10 35599471
2021 Distinct role of histone chaperone Asf1a and Asf1b during fertilization and pre-implantation embryonic development in mice. Epigenetics & chromatin 10 34906203
2023 Knockdown of ASF1B inhibits cell proliferation, migration, invasion and cisplatin resistance in gastric cancer through the Myc pathway. Oncology letters 6 37153049
2022 miR-24-3p Regulates Epithelial-Mesenchymal Transition and the Malignant Phenotype of Pancreatic Adenocarcinoma by Regulating ASF1B Expression. Biochemical genetics 6 36114946
2022 The circCDK17/miR-122-5p/ASF1B axis regulates the progression of cervical cancer. Histology and histopathology 6 36178207
2022 miR-767-3p suppresses melanoma progression by inhibiting ASF1B expression. Biochemical and biophysical research communications 5 36007337
2023 The interaction between ASF1B and TLK1 promotes the malignant progression of low-grade glioma. Annals of medicine 4 36947060
2024 Carcinogenic Role and Clinical Significance of Histone H3-H4 Chaperone Anti-silencing Function 1 B (ASF1B) in Lung Adenocarcinoma. Journal of Cancer 3 38164276
2025 ASF1B promotes gastric cancer progression by modulating H2AC20 and activating PI3K/AKT and ERK1/2 pathways. Frontiers in pharmacology 2 40041497
2026 ASF1B promotes gastric cancer liver metastasis through inhibiting ZDHHC9/PCBP1/ SLC7A11 signaling axis mediated ferroptosis. NPJ precision oncology 1 41535416
2026 ASF1B promotes erythropoiesis by regulating the establishment and enrichment of H3.3 nucleosomes. Nucleic acids research 0 42100853
2026 Ablation of ASF1B mitigates the proliferation of A549 cells and enhances anti-PD-L1 therapy by regulating ferroptosis. Tissue & cell 0 42114389
2026 A Feedback Loop Driven by H3K18la and ASF1B via the LINC02732-miR-1291 Axis Promotes Hepatocellular Carcinoma Proliferation. Cells 0 42193960
2025 APOBEC3B/ASF1B-TGF-β signaling axis promotes epithelial-mesenchymal transition in HPV-positive oropharyngeal cancer. Journal of dental sciences 0 41585149
2021 LINC00665 Promotes the Progression of Multiple Myeloma by Adsorbing miR-214-3p and Positively Regulating the Expression of PSMD10 and ASF1B [Retraction]. OncoTargets and therapy 0 34103943

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