Affinage

ASF1A

Histone chaperone ASF1A · UniProt Q9Y294

Length
204 aa
Mass
23.0 kDa
Annotated
2026-06-09
31 papers in source corpus 24 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASF1A is a histone H3-H4 chaperone that operates across replication-independent chromatin assembly, DNA damage signaling, and transcriptional regulation (PMID:21807893, PMID:28943310). In its core assembly role, ASF1A is a member of the HIRA/UBN1/CABIN1/ASF1a (HUCA) quaternary complex in which HIRA serves as scaffold to assemble UBN1, CABIN1, and ASF1a for replication-independent deposition of histone variant H3.3 (PMID:19029251, PMID:21807893); this complex is rate-limiting for senescence-associated heterochromatin foci (SAHF) and senescence-associated cell-cycle exit, and HIRA's transit through PML nuclear bodies is required for SAHF formation (PMID:15621527, PMID:17242198). Structurally, HIRA binds the ASF1a beta-sandwich through an antiparallel B-domain beta-hairpin, and CAF-1 p60 uses B-domain-like motifs to compete for the same surface, making downstream-chaperone engagement mutually exclusive (PMID:16980972); in nucleosome assembly ASF1a acts with sNASP, which positions H3 upstream and forms a quaternary complex that folds the H3-H4 dimer (PMID:28123037). The chaperone surface is competitively occupied and inhibited by CODANIN-1 (CDAN1), which engages ASF1A via B-domains and histone H3 mimic helices, blocking ASF1/H3-H4 complex formation and sequestering ASF1A in the cytoplasm. Beyond assembly, ASF1A has a chaperone-independent role in DNA double-strand break repair: it is recruited to breaks, interacts with MDC1, and facilitates ATM-mediated MDC1 phosphorylation to drive RNF8/RNF168-dependent histone ubiquitination, 53BP1 recruitment, and NHEJ, a function specific to ASF1a over ASF1b and promoted by Chk1-mediated phosphorylation at Ser-166 (PMID:28943310, PMID:33503415). ASF1A protein levels are set by ubiquitin-dependent turnover, opposed by USP52-mediated deubiquitination and stabilization, and by ATR/CRL1(βTRCP)-dependent degradation at stalled replication forks (PMID:29599486, PMID:24700029). As a transcriptional coactivator, ASF1A promotes H3K56 acetylation at Notch target promoters to enhance RBPJ binding and cooperates with P300 to regulate H3K18 lactylation, while in development its histone-interaction activity resolves bivalent chromatin domains during ES-cell differentiation and assembles H3.3 in the paternal pronucleus (PMID:36184659, PMID:39027248, PMID:29915027, PMID:34906203).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2005 High

    Established that ASF1a physically partners with HIRA and that this complex is rate-limiting for forming senescence-associated heterochromatin and driving senescence cell-cycle exit, defining ASF1a's role in replication-independent chromatin remodeling.

    Evidence Co-IP, dominant-negative mutants, and siRNA with colocalization in primary human cells approaching senescence

    PMID:15621527

    Open questions at the time
    • Did not define the full subunit composition of the complex
    • Mechanism of HIRA entry into PML bodies left open
  2. 2006 High

    Resolved the structural basis of ASF1a partner selection, showing the HIRA B-domain and CAF-1 p60 compete for the same beta-sandwich surface, explaining mutually exclusive downstream-chaperone routing.

    Evidence X-ray crystallography of the ASF1a-HIRA heterodimer with biochemical competition and mutagenesis

    PMID:16980972

    Open questions at the time
    • No structure of the full quaternary complex
    • Determinants of ASF1a vs ASF1b differential affinity only partly mapped
  3. 2008 High

    Identified UBN1 as a direct HIRA-binding component of the complex linked to H3K9 methyltransferase activity at repressed genes, extending the senescence assembly machinery beyond ASF1a and HIRA.

    Evidence Co-IP, recombinant protein binding, siRNA, and ChIP

    PMID:19029251

    Open questions at the time
    • How UBN1 directs histone deposition versus methyltransferase recruitment unresolved
  4. 2011 High

    Completed the HUCA quaternary complex by adding CABIN1 with HIRA as scaffold and showed it preferentially deposits H3.3 in a replication-independent manner; parallel work placed the HIRA/ASF1a pathway alongside pRB and p53 in SAHF formation and dissected HIRA-specific roles in ALT bodies.

    Evidence Reconstitution from recombinant proteins, endogenous Co-IP, epistasis analysis, and comparative HIRA vs ASF1a knockdown in senescent and ALT cells

    PMID:17242198 PMID:21347226 PMID:21807893

    Open questions at the time
    • Stoichiometry and assembly order within HUCA not fully defined
    • ASF1a contribution to H3.3 deposition separable from HIRA only partially addressed
  5. 2011 Medium

    Linked ASF1a to recovery from the DNA damage checkpoint by showing it restores H3K56 acetylation after UV repair, enabling γ-H2AX dephosphorylation, while leaving repair itself ASF1a-independent.

    Evidence siRNA, ChIP, and γ-H2AX immunofluorescence in UV-irradiated human cells

    PMID:21727091

    Open questions at the time
    • Acetyltransferase responsible for H3K56Ac restoration not identified here
    • Mechanistic coupling of H3K56Ac to phosphatase activity unclear
  6. 2012 Medium

    Extended ASF1a's chaperone function to host-pathogen chromatin, showing it assembles chromatin on incoming HSV-1 DNA to restrain immediate-early transcription and viral replication.

    Evidence siRNA, MNase protection, RT-PCR, and viral growth assays in HeLa cells

    PMID:22951827

    Open questions at the time
    • Which downstream chaperone partner deposits histones on viral DNA not defined
    • Direct vs indirect effect on IE transcription not separated
  7. 2013 Medium

    Provided the evolutionary and biochemical basis for ASF1a/ASF1b subfunctionalization, mapping N- and C-terminal regions outside the H3-H4 surface as determinants of preferential downstream-chaperone partnering.

    Evidence Biochemical binding assays, evolutionary and structural comparison

    PMID:23645555

    Open questions at the time
    • Functional consequences of MCM9-intronic genomic relocation not tested in cells
  8. 2014 Medium

    Defined two layers of ASF1A regulation and function: ATR/CRL1(βTRCP)-mediated degradation that drives dechromatinization at stalled forks, and an essential requirement for reprogramming somatic cells to pluripotency.

    Evidence Ubiquitination assays with ATR/CRL1βTRCP perturbation; oocyte localization plus loss/gain-of-function reprogramming assays

    PMID:24700029 PMID:25035411

    Open questions at the time
    • Whether dechromatinization is purely degradation-driven or also active not resolved
    • Molecular target genes reprogrammed by ASF1A not mapped
  9. 2015 Medium

    Identified the degradation machinery for ASF1A, showing the conserved E2 RAD6 cooperates with E3 MDM2 to drive ubiquitin-proteasome turnover.

    Evidence Co-IP, in vitro interaction, and ubiquitination assays in Drosophila and human cells

    PMID:26336826

    Open questions at the time
    • Ubiquitination site(s) on ASF1A not mapped
    • Signals triggering RAD6/MDM2-dependent turnover unknown
  10. 2016 High

    Placed ASF1A within reconstituted mismatch repair and the upstream folding pathway, showing CAF-1/ASF1A-H3-H4 deposition is gated by MutSα and that sNASP and ASF1A together fold the H3-H4 dimer; in parallel ASF1a was tied to innate immunity via CBP-dependent H3K56ac at the Ifnb promoter.

    Evidence Fully reconstituted in vitro MMR and tetrasome assays; in vitro H3-H4 folding/binding assays; Co-IP, ChIP, and IFN-β assays in macrophages

    PMID:26945061 PMID:27596240 PMID:28123037

    Open questions at the time
    • In vivo relevance of MMR-coupled tetrasome deposition not shown
    • Whether sNASP-ASF1A folding feeds all downstream chaperones untested
  11. 2017 High

    Revealed a chaperone-independent role for ASF1a in NHEJ, where it recruits to DSBs and promotes ATM-mediated MDC1 phosphorylation to trigger RNF8/RNF168 ubiquitination and 53BP1 recruitment, with specificity over ASF1b.

    Evidence Reciprocal Co-IP, siRNA, ChIP, NHEJ assays, foci analysis, and chaperone-dead mutant in human cells

    PMID:28943310

    Open questions at the time
    • How ASF1a is recruited to breaks not fully defined here
    • Structural basis of ASF1a-MDC1 interaction unknown
  12. 2018 High

    Identified USP52 as the deubiquitinase opposing ASF1A turnover, stabilizing it to support chromatin assembly and cell-cycle progression, and separately established that ASF1a histone-interaction activity resolves bivalent chromatin during ES-cell differentiation.

    Evidence In vitro DUB assay, Co-IP, ubiquitination assays in breast cancer cells; CRISPR deletion, ChIP, and domain-specific mutants in mouse ES cells

    PMID:29599486 PMID:29915027

    Open questions at the time
    • Transcription factors recruiting ASF1a to bivalent promoters only partly identified
    • Balance between USP52 and RAD6/MDM2 in setting ASF1A levels not quantified
  13. 2019 Medium

    Linked ASF1A loss to anti-tumor outcomes, showing its inhibition triggers p53-p21-dependent senescence in WT-p53 cancers and reprograms the tumor microenvironment toward immunogenic macrophages, synergizing with anti-PD-1.

    Evidence siRNA with p53-inhibitor epistasis and DNA damage markers; in vivo CRISPR screen, KO, and immune phenotyping in KRAS-mutant lung adenocarcinoma

    PMID:30692519 PMID:31744829

    Open questions at the time
    • Direct cause of DNA damage upon ASF1A loss not pinpointed
    • Mechanism connecting ASF1A loss to GM-CSF upregulation undefined
  14. 2021 High

    Defined the kinase signaling that activates ASF1A's NHEJ role, showing Chk1 (downstream of ATM) directly phosphorylates Ser-166 to enable the MDC1-ATM interaction in G1, and established ASF1a-specific H3.3 assembly in the paternal pronucleus.

    Evidence In vitro kinase assay, phospho-specific antibody, Co-IP, and NHEJ/foci assays in G1-arrested cells; morpholino knockdown with immunofluorescence in mouse embryos

    PMID:33503415 PMID:34906203

    Open questions at the time
    • Whether Ser-166 phosphorylation affects chaperone roles untested
    • Distinct mechanisms of Asf1a vs Asf1b in embryogenesis only partly resolved
  15. 2022 Medium

    Established ASF1A as a transcriptional coactivator for Notch, depositing H3K56ac at target promoters to enhance RBPJ binding and enforce differentiation arrest in CML blast crisis.

    Evidence Co-IP, ChIP for H3K56ac and RBPJ, knockdown, and in vivo CML model

    PMID:36184659

    Open questions at the time
    • Acetyltransferase recruited by ASF1A at Notch promoters not identified
    • Direct ASF1A-RBPJ contacts not mapped
  16. 2024 High

    Expanded ASF1A coactivator function to histone lactylation and resolved the structural basis of its inhibition, showing ASF1A partners P300 to regulate H3K18la at SNAI1 driving EndMT in atherosclerosis, while CDAN1 sequesters ASF1A in the cytoplasm via B-domains and H3 mimic helices to block H3-H4 binding.

    Evidence Co-IP, ChIP for H3K18la, endothelial-specific Asf1a KO in Apoe-null mice; cryo-EM of the CDAN1-ASF1A complex with biochemical reconstitution (preprint)

    PMID:39027248

    Open questions at the time
    • How P300 and ASF1A jointly select lactylation targets unclear
    • Cellular triggers controlling CDAN1-mediated cytoplasmic sequestration undefined
  17. 2025 Medium

    Identified Sp100A as the driver of HUCA complex targeting to PML nuclear bodies, connecting an upstream localization determinant to ASF1a's senescence-associated chromatin functions.

    Evidence CRISPR Sp100 knockout with immunofluorescence and isoform-specific rescue in keratinocytes (preprint)

    Open questions at the time
    • Single preprint not independently confirmed
    • Functional consequence of failed PML-NB localization for SAHF not tested here

Open questions

Synthesis pass · forward-looking unresolved questions
  • How ASF1A's multiple roles — H3.3/H3-H4 chaperoning, chaperone-independent NHEJ signaling, and transcriptional coactivation via distinct histone modifications — are coordinately partitioned within a single cell and switched between contexts remains unresolved.
  • No unified model integrating chaperone vs non-chaperone functions
  • Determinants directing ASF1A to assembly vs repair vs transcription unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 4 GO:0140110 transcription regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2 GO:0005829 cytosol 2
Pathway
R-HSA-4839726 Chromatin organization 3 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
CABIN1CDAN1EP300HIRAMDC1RAD6UBN1USP52
Complex memberships
CDAN1-ASF1A complexHUCA (HIRA/UBN1/CABIN1/ASF1a)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 ASF1a forms a physical complex with HIRA that is rate-limiting for formation of macroH2A-containing senescence-associated heterochromatin foci (SAHF) and onset of senescence-associated cell cycle exit. As cells approach senescence, HIRA enters PML nuclear bodies where it transiently colocalizes with HP1 proteins prior to HP1 incorporation into SAHF; ASF1a is required for efficient SAHF formation and senescence-associated cell cycle exit. Co-immunoprecipitation, dominant-negative mutants, siRNA knockdown, immunofluorescence/colocalization in primary human cells approaching senescence Developmental cell High 15621527
2006 Crystal structure of ASF1a-HIRA heterodimer shows the HIRA B domain forms an antiparallel beta-hairpin binding perpendicular to the beta-sandwich of ASF1a via beta-sheet, salt bridge, and van der Waals contacts. The N- and C-terminal regions of ASF1a and ASF1b determine differential affinity for HIRA. CAF-1 p60 uses B domain-like motifs to competitively bind ASF1a, mutually exclusive with HIRA binding. X-ray crystallography, biochemical binding assays, mutational analysis Nature structural & molecular biology High 16980972
2007 HIRA/ASF1a pathway cooperates with pRB and p53 in parallel to form SAHF; the HIRA/ASF1a and pRB pathways converge through the DNAJ-domain protein DNAJA2. HIRA's localization to PML bodies is required for SAHF formation, but this translocation occurs independently of functional pRB and p53. Dominant-negative HIRA mutants, PML-RARα disruption of PML bodies, epistasis analysis, co-immunoprecipitation in primary human cells Molecular and cellular biology High 17242198
2008 UBN1 (human ortholog of yeast Hpc2p) is a component of the HIRA/ASF1a chromatin-remodeling complex. The Hpc2-related domain (HRD) of UBN1 directly interacts with the N-terminal WD repeats of HIRA. UBN1 is indispensable for SAHF formation and associates with histone H3K9 methyltransferase activity at proliferation-promoting genes repressed in senescence. Co-immunoprecipitation, direct binding assays with recombinant proteins, siRNA knockdown, chromatin immunoprecipitation Molecular and cellular biology High 19029251
2011 ASF1a is required for post-UV-repair restoration of H3K56 acetylation (H3K56Ac), which in turn is needed for dephosphorylation of γ-H2AX and cellular recovery from checkpoint arrest. ATM checkpoint kinase regulates H3K56Ac restoration. Completion of DNA damage repair itself is not dependent on ASF1a or H3K56Ac. siRNA knockdown, chromatin immunoprecipitation, immunofluorescence for γ-H2AX in UV-irradiated human cells Nucleic acids research Medium 21727091
2011 CABIN1 is a functional fourth member of the human HIRA/UBN1/ASF1a (HUCA) quaternary complex. HIRA acts as a scaffold to assemble UBN1, ASF1a, and CABIN1. The HUCA complex preferentially deposits histone variant H3.3 into chromatin in a DNA replication-independent manner, and CABIN1 is involved in heterochromatinization of senescent cells. Co-immunoprecipitation at endogenous and ectopic expression levels, reconstitution of quaternary complex from recombinant proteins, mutational analysis, chromatin fractionation Molecular and cellular biology High 21807893
2011 HIRA, but not ASF1a, is required for HP1-mediated formation of ALT-associated PML bodies (APBs) and large HP1 foci following p53/p21 pathway activation in ALT cells. HIRA and ASF1a co-localize inside PML bodies in normal fibroblasts approaching senescence, confirming a senescence-associated ASF1a/HIRA complex inside PML bodies. siRNA knockdown of HIRA vs. ASF1a, immunofluorescence, colocalization in ALT cells and normal fibroblasts PloS one Medium 21347226
2012 ASF1a is required for chromatin assembly onto incoming herpes simplex virus 1 (HSV-1) DNA early during lytic infection. ASF1a knockdown reduced viral DNA protection from MNase digestion, increased transcription of immediate early genes ICP0 and ICP4 at 3 hpi, and decreased viral replication and growth. siRNA knockdown, MNase protection assay, RT-PCR, viral growth assay in HeLa cells Journal of virology Medium 22951827
2013 ASF1a and ASF1b underwent subfunctionalization after vertebrate duplication. Regions outside the primary H3-H4 interaction surface (N- and C-terminal regions) determine preferential interactions of ASF1a versus ASF1b with distinct downstream H3-H4 chaperone complexes. ASF1a was relocated into an intron of MCM9 in tetrapod ancestors, providing a different genomic environment and replication timing context. Biochemical binding assays, evolutionary analysis, structural comparison Molecular biology and evolution Medium 23645555
2014 Doxorubicin activates the ATR checkpoint pathway, which causes CRL1(βTRCP)-dependent ubiquitination and proteasomal degradation of ASF1a, leading to localized dechromatinization and repression of genes overlapping with clusters of stalled replication forks. Western blotting, ubiquitination assays, ATR inhibition and CRL1(βTRCP) dominant-negative studies, chromatin fractionation, gene expression analysis in cancer cells Genes & development Medium 24700029
2014 ASF1A is specifically enriched in the metaphase II human oocyte and is necessary for reprogramming of human adult dermal fibroblasts into iPSCs. Overexpression of ASF1A together with OCT4 in fibroblasts exposed to the oocyte-specific paracrine factor GDF9 is sufficient to reprogram them into pluripotent cells. Immunofluorescence localization, loss-of-function (knockdown), overexpression/reprogramming assay, iPSC characterization Science (New York, N.Y.) Medium 25035411
2015 The E2 ubiquitin-conjugating enzyme RAD6 is an evolutionarily conserved interacting protein of ASF1 that cooperates with the E3 ligase MDM2 to promote ubiquitin-proteasome-dependent turnover of ASF1A in human cells. Co-immunoprecipitation, ubiquitination assays, in vitro interaction studies in Drosophila and human cells Oncotarget Medium 26336826
2016 In reconstituted human systems, MutSα inhibits CAF-1- and ASF1A-H3-H4-dependent packaging of a DNA mismatch into a tetrasome, supporting that MMR occurs before mismatch packaging into the tetrasome. Additionally, CAF-1- and ASF1A-H3-H4-dependent deposition of histone (H3-H4)2 tetramers suppresses unnecessary degradation of the discontinuous strand during MMR reactions. Reconstituted in vitro systems with purified human proteins (MMR, CAF-1, ASF1A-H3-H4), tetrasome deposition assays, strand degradation assays The Journal of biological chemistry High 26945061
2016 sNASP contains at least two histone interaction sites, beyond the TPR-H3 peptide site that overlaps the ASF1A-H3-H4 interface, that are compatible with simultaneous ASF1A binding, allowing sNASP and ASF1A to form a quaternary complex with H3-H4. sNASP makes a specific complex with H3 alone in vitro (but not H4), suggesting it acts upstream of ASF1A in the nucleosome assembly pathway. Together, sNASP and ASF1A can fold an H3-H4 dimer in vitro. In vitro binding assays, pull-down, analytical biochemistry, reconstitution of H3-H4 folding in vitro Nucleic acids research High 28123037
2016 ASF1a associates with the acetyltransferase CBP and promotes H3K56 acetylation at the Ifnb promoter following VSV infection in macrophages, thereby enhancing IFN-β production. ASF1a is induced in VSV-infected macrophages in an IRF3-dependent manner. Co-immunoprecipitation, chromatin immunoprecipitation, siRNA knockdown, IFN-β production assays in macrophages Molecular immunology Medium 27596240
2017 ASF1a interacts with MDC1 and is recruited to sites of DSBs, where it facilitates the interaction of phospho-ATM with MDC1 and phosphorylation of MDC1. This enables recruitment of RNF8/RNF168 ubiquitin ligases, histone ubiquitination, 53BP1 recruitment, and NHEJ. ASF1a deficiency reduces NHEJ and sensitizes cells to DSBs. This role is specific to ASF1a (not ASF1b) and does not require its histone chaperone activity. Co-immunoprecipitation, siRNA knockdown, ChIP, NHEJ assays, γ-H2AX foci, 53BP1 foci, DSB sensitivity assays Molecular cell High 28943310
2018 USP52 is a bona fide deubiquitinase that physically associates with ASF1A and promotes ASF1A deubiquitination and stabilization, thereby facilitating chromatin assembly and cell cycle progression. USP52-promoted ASF1A stabilization sensitizes cells to DNA damage when impaired. Co-immunoprecipitation, in vitro deubiquitinase assay, ubiquitination assays, siRNA knockdown, overexpression studies in breast cancer cells Nature communications High 29599486
2018 Asf1a is recruited to bivalent chromatin promoters (partially through association with transcription factors) and mediates nucleosome disassembly during ES cell differentiation. The Asf1a-histone interaction (not nucleosome assembly activity) is required for resolution of bivalent domains and activation of lineage-specific genes. Deletion of Asf1a compromises lineage-specific gene expression but does not affect silencing of pluripotent genes. CRISPR deletion, chromatin immunoprecipitation, nucleosome disassembly assays, gene expression analysis, domain-specific mutants in mouse ES cells Proceedings of the National Academy of Sciences of the United States of America High 29915027
2019 ASF1a inhibition in tumor cells induces immunogenic macrophage differentiation in the tumor microenvironment by upregulating GM-CSF expression, and potentiates T-cell activation in combination with anti-PD-1 therapy in KRAS-mutant lung adenocarcinoma. In vivo CRISPR screen, genetic deletion (CRISPR KO), tumor microenvironment analysis, cytokine measurement (GM-CSF), immune cell phenotyping Cancer discovery Medium 31744829
2019 ASF1a inhibition in cancer cells with wild-type p53 induces widespread DNA damage, leading to robust upregulation of p53 and p21cip1 expression and cellular senescence. p53 inhibition attenuates the p21cip1 induction caused by ASF1a depletion, placing ASF1a upstream of the p53-p21 axis. siRNA knockdown, DNA damage markers (γ-H2AX), flow cytometry for senescence, p53 inhibitor epistasis, Western blotting in HCC and prostate cancer cells Cell death & disease Medium 30692519
2021 Chk1, activated by ATM kinase at DNA breaks in G1, directly phosphorylates ASF1A at Ser-166. ASF1A phosphorylated at Ser-166 interacts with MDC1, enhancing MDC1's interaction with ATM and stable ATM localization at DSBs. This promotes downstream histone ubiquitination, 53BP1 recruitment, and NHEJ in G1. This role of ASF1A in NHEJ is independent of its histone chaperone activity. In vitro kinase assay, phospho-specific antibody, Co-immunoprecipitation, siRNA knockdown, NHEJ assays, 53BP1/γ-H2AX foci in G1-arrested cells Cell reports High 33503415
2021 Asf1a, but not Asf1b, is required for assembly of histone H3.3 in paternal pronuclei after fertilization in mice. Asf1a knockdown severely reduces H3K56 acetylation levels and Oct4 expression in blastocyst-stage embryos. Both Asf1a and Asf1b are required for pre-implantation embryonic development, but through distinct mechanisms. Morpholino knockdown, immunofluorescence for H3.3, H3K56ac, Oct4 and PCNA in mouse embryos Epigenetics & chromatin Medium 34906203
2022 ASF1A acts as a coactivator of the Notch transcriptional complex, inducing H3K56ac modification at promoters of Notch target genes and enhancing RBPJ binding to these promoters, thereby activating Notch signaling and mediating differentiation arrest in CML blast crisis cells. Co-immunoprecipitation, ChIP for H3K56ac and RBPJ, siRNA/shRNA knockdown, in vivo CML model, gene expression analysis Cell death & disease Medium 36184659
2024 ASF1A was identified as a cofactor of the acetyltransferase P300 that precisely regulates the enrichment of H3K18 lactylation (H3K18la) at the SNAI1 promoter, thereby activating SNAI1 transcription and promoting endothelial-to-mesenchymal transition (EndMT) in atherosclerosis. Endothelium-specific ASF1A deletion inhibited EndMT and alleviated atherosclerosis in Apoe KO mice. Co-immunoprecipitation (ASF1A-P300 complex), ChIP for H3K18la at SNAI1 promoter, endothelial-specific Asf1a knockout mouse model (Apoe KO Asf1a ECKO), in vitro EndMT assays Acta pharmaceutica Sinica. B High 39027248
2024 Cryo-EM structure of the CODANIN-1 (CDAN1)–ASF1A complex at 3.75 Å resolution reveals that CDAN1 forms a dimer where each monomer holds two ASF1 molecules using two B-domains and two histone H3 mimic helices (HMHs). Interaction via the HMH and B-domains blocks formation of the ASF1/H3-H4 complex and sequesters ASF1A in the cytoplasm, inhibiting nucleosome assembly. Single-particle cryo-EM, biochemical reconstitution, binding assays bioRxivpreprint High
2024 CDAN1 dimerizes and forms cytosolic complexes with CDIN1 and multiple copies of ASF1A/B. Cryo-EM structures show CDAN1 engages ASF1 via two B-domains and two helices that mimic histone H3 binding, allowing one CDAN1 to recruit two ASF1 molecules. ASF1A and ASF1B have different requirements for CDAN1 engagement. This sequesters and inhibits ASF1A chaperone function. Single-particle cryo-EM, biochemical reconstitution, in vitro binding assays, comparative ASF1A vs ASF1B analysis bioRxivpreprint High
2025 ASF1a (as part of the HIRA complex) fails to localize to PML nuclear bodies in Sp100 knockout keratinocytes even after interferon stimulation. The Sp100A isoform (via its SUMO-interacting motif) is the primary driver of HIRA/UBN1/ASF1a complex localization to PML-NBs. CRISPR-Cas9 Sp100 knockout, immunofluorescence for HIRA/UBN1/ASF1a at PML-NBs, isoform-specific rescue experiments bioRxivpreprint Medium

Source papers

Stage 0 corpus · 31 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Formation of MacroH2A-containing senescence-associated heterochromatin foci and senescence driven by ASF1a and HIRA. Developmental cell 556 15621527
2019 In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma. Cancer discovery 181 31744829
2006 Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly. Nature structural & molecular biology 158 16980972
2007 Definition of pRB- and p53-dependent and -independent steps in HIRA/ASF1a-mediated formation of senescence-associated heterochromatin foci. Molecular and cellular biology 128 17242198
2008 Human UBN1 is an ortholog of yeast Hpc2p and has an essential role in the HIRA/ASF1a chromatin-remodeling pathway in senescent cells. Molecular and cellular biology 104 19029251
2011 Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex. Molecular and cellular biology 90 21807893
2024 ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT. Acta pharmaceutica Sinica. B 88 39027248
2014 Cell reprogramming. Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming. Science (New York, N.Y.) 68 25035411
2020 LncRNA XIST serves as a ceRNA to regulate the expression of ASF1A, BRWD1M, and PFKFB2 in kidney transplant acute kidney injury via sponging hsa-miR-212-3p and hsa-miR-122-5p. Cell cycle (Georgetown, Tex.) 67 31914881
2011 ASF1A and ATM regulate H3K56-mediated cell-cycle checkpoint recovery in response to UV irradiation. Nucleic acids research 59 21727091
2013 Subfunctionalization via adaptive evolution influenced by genomic context: the case of histone chaperones ASF1a and ASF1b. Molecular biology and evolution 55 23645555
2012 Cell-cycle-regulated control of VSG expression site silencing by histones and histone chaperones ASF1A and CAF-1b in Trypanosoma brucei. Nucleic acids research 52 22941664
2018 USP52 acts as a deubiquitinase and promotes histone chaperone ASF1A stabilization. Nature communications 42 29599486
2012 Transcriptional profiling of human familial longevity indicates a role for ASF1A and IL7R. PloS one 39 22247756
2017 ASF1a Promotes Non-homologous End Joining Repair by Facilitating Phosphorylation of MDC1 by ATM at Double-Strand Breaks. Molecular cell 35 28943310
2012 Identification of an ubinuclein 1 region required for stability and function of the human HIRA/UBN1/CABIN1/ASF1a histone H3.3 chaperone complex. Biochemistry 32 22401310
2019 ASF1a inhibition induces p53-dependent growth arrest and senescence of cancer cells. Cell death & disease 29 30692519
2016 DNA Mismatch Repair Interacts with CAF-1- and ASF1A-H3-H4-dependent Histone (H3-H4)2 Tetramer Deposition. The Journal of biological chemistry 29 26945061
2018 Asf1a resolves bivalent chromatin domains for the induction of lineage-specific genes during mouse embryonic stem cell differentiation. Proceedings of the National Academy of Sciences of the United States of America 27 29915027
2014 ATR checkpoint kinase and CRL1βTRCP collaborate to degrade ASF1a and thus repress genes overlapping with clusters of stalled replication forks. Genes & development 26 24700029
2011 HP1-mediated formation of alternative lengthening of telomeres-associated PML bodies requires HIRA but not ASF1a. PloS one 26 21347226
2012 Chromatin assembly on herpes simplex virus 1 DNA early during a lytic infection is Asf1a dependent. Journal of virology 25 22951827
2016 sNASP and ASF1A function through both competitive and compatible modes of histone binding. Nucleic acids research 23 28123037
2015 A conserved RAD6-MDM2 ubiquitin ligase machinery targets histone chaperone ASF1A in tumorigenesis. Oncotarget 14 26336826
2021 Chk1 promotes non-homologous end joining in G1 through direct phosphorylation of ASF1A. Cell reports 12 33503415
2020 Small-molecule arone protects from neuroinflammation in LPS-activated microglia BV-2 cells by targeting histone-remodeling chaperone ASF1a. Biochemical pharmacology 11 32222456
2021 Distinct role of histone chaperone Asf1a and Asf1b during fertilization and pre-implantation embryonic development in mice. Epigenetics & chromatin 10 34906203
2022 Histone chaperone ASF1A accelerates chronic myeloid leukemia blast crisis by activating Notch signaling. Cell death & disease 8 36184659
2016 ASF1a enhances antiviral immune response by associating with CBP to mediate acetylation of H3K56 at the Ifnb promoter. Molecular immunology 8 27596240
2015 Roles of p53 and ASF1A in the Reprogramming of Sheep Kidney Cells to Pluripotent Cells. Cellular reprogramming 7 26580119
2019 ASF1A regulates H4Y72 phosphorylation and promotes autophagy in colon cancer cells via a kinase activity. Artificial cells, nanomedicine, and biotechnology 5 31286799

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