Affinage

ASF1A

Histone chaperone ASF1A · UniProt Q9Y294

Length
204 aa
Mass
23.0 kDa
Annotated
2026-04-28
100 papers in source corpus 25 papers cited in narrative 25 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ASF1A is a histone H3-H4 chaperone that disrupts H3-H4 tetramers via its β-sandwich domain and participates in both replication-coupled and replication-independent chromatin assembly as part of the quaternary HIRA/UBN1/CABIN1/ASF1a (HUCA) complex, functioning in senescence-associated heterochromatin foci (SAHF) formation, bivalent chromatin resolution during differentiation, and histone eviction at active promoters in concert with the TFIID subunit TAF1/CCG1 (PMID:15621527, PMID:17293877, PMID:21807893, PMID:29915027, PMID:20393127). Independent of its histone chaperone activity, ATM-activated Chk1 phosphorylates ASF1A at Ser-166, enabling interaction with MDC1 to stabilize ATM at double-strand breaks and promote RNF8/RNF168-mediated histone ubiquitination, 53BP1 recruitment, and non-homologous end joining (PMID:28943310, PMID:33503415). ASF1A protein abundance is regulated by USP52-mediated deubiquitination and by ATR/CRL1(βTRCP)- and RAD6/MDM2-dependent ubiquitin-proteasome degradation (PMID:29599486, PMID:24700029, PMID:26336826). ASF1A also functions as a P300 cofactor directing H3K18 lactylation at specific promoters to activate transcription, with endothelial Asf1a deletion attenuating endothelial-to-mesenchymal transition and atherosclerosis in vivo (PMID:39027248).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Establishing that ASF1A physically and functionally links histone chaperoning to TFIID-dependent transcription resolved how a histone chaperone interfaces with the basal transcription machinery.

    Evidence GST pull-down and Co-IP of human ASF1a with TAF1/CCG1 bromodomains; synthetic lethality and Spt suppression in yeast orthologs

    PMID:12093919

    Open questions at the time
    • No structural detail of the ASF1a–TAF1 interface at this stage
    • Unclear which histone PTMs gate the interaction in vivo
  2. 2005 High

    Demonstrating that the ASF1a–HIRA complex is rate-limiting for SAHF formation and senescence-associated cell cycle exit placed ASF1a in a defined chromatin-remodeling pathway controlling cellular senescence.

    Evidence Reciprocal Co-IP of HIRA–ASF1a; siRNA knockdown of ASF1a with SAHF and cell cycle exit readouts; immunofluorescence showing PML body flux

    PMID:15621527

    Open questions at the time
    • Identity of additional HUCA subunits not yet known
    • Mechanism of PML body transit unresolved
  3. 2006 High

    The crystal structure of the ASF1a–HIRA B-domain heterodimer revealed the molecular basis for ASF1a's preferential partnership with HIRA over CAF-1, explaining paralog subfunctionalization at the structural level.

    Evidence X-ray crystallography; ITC and competition pull-downs; mutagenesis showing CAF-1 p60 competes via a B-domain-like motif

    PMID:16980972

    Open questions at the time
    • Full quaternary HUCA complex architecture unresolved
    • No in vivo validation of competition dynamics
  4. 2007 High

    The 2.7 Å crystal structure of ASF1a bound to H3-H4 established the mechanism of tetramer disruption: the H4 C-terminal β-strand switches from H2A to ASF1a, defining the core histone chaperone activity.

    Evidence X-ray crystallography; in vitro tetramer disruption assay; structure-guided mutagenesis with transcriptional readouts

    PMID:17293877

    Open questions at the time
    • How ASF1a hands off H3-H4 dimers to downstream chaperones not yet reconstituted
  5. 2008 High

    Identification of UBN1 as an essential HUCA subunit that binds HIRA's WD repeats and targets senescence gene promoters expanded the complex from a dimer to a multi-subunit assembly with gene-specific chromatin roles.

    Evidence Co-IP of endogenous complex; recombinant binding assays; siRNA with SAHF readout; ChIP at proliferation genes

    PMID:19029251

    Open questions at the time
    • CABIN1 not yet placed in the complex
    • Stoichiometry uncertain
  6. 2010 High

    The crystal structure of ASF1a with the TAF1 double bromodomain provided a structural mechanism linking histone acetylation recognition to ASF1a-mediated histone eviction and RNA Pol II entry at promoters.

    Evidence 3.3 Å crystal structure; Co-IP; ChIP for histone occupancy and Pol II at active promoters

    PMID:20393127

    Open questions at the time
    • Genome-wide scope of ASF1a–TAF1-dependent promoter clearance not tested
    • Kinetics of eviction in vivo unknown
  7. 2011 High

    Reconstitution of the quaternary HUCA complex (HIRA/UBN1/CABIN1/ASF1a) with HIRA as scaffold, and demonstration that ASF1a restores H3K56Ac post-UV damage for checkpoint recovery, expanded ASF1a's roles to both complex assembly and DNA damage recovery.

    Evidence Recombinant quaternary complex reconstitution; reciprocal Co-IP of CABIN1; siRNA of ASF1a with H3K56Ac, γ-H2AX, and checkpoint recovery readouts; ATM inhibition epistasis

    PMID:21727091 PMID:21807893

    Open questions at the time
    • How H3K56Ac restoration is coordinated with nucleosome reassembly in vivo
    • Whether CABIN1 contributes to the DNA damage function
  8. 2014 High

    Discovery that ATR triggers CRL1(βTRCP)-mediated proteasomal degradation of ASF1a during replication stress, and that ASF1a overexpression with OCT4/GDF9 suffices for somatic cell reprogramming, revealed regulated ASF1a turnover and a role in pluripotency.

    Evidence Doxorubicin-induced replication stress with proteasome inhibitor rescue and CRL1/ATR epistasis; ASF1a overexpression reprogramming assay with pluripotency markers

    PMID:24700029 PMID:25035411

    Open questions at the time
    • Degron motif on ASF1a for βTRCP not mapped
    • Mechanism by which ASF1a enables reprogramming beyond chromatin remodeling unclear
  9. 2016 High

    Reconstituted systems showed ASF1A cooperates with CAF-1 for (H3-H4)₂ tetrasome deposition during DNA replication, and that sNASP acts upstream of ASF1A to fold H3-H4 dimers, defining the histone chaperone relay.

    Evidence Fully reconstituted in vitro MMR and nucleosome assembly; sNASP–ASF1A–H3–H4 quaternary complex by native gel; histone folding assay

    PMID:26945061 PMID:28123037

    Open questions at the time
    • In vivo order of hand-off from sNASP to ASF1A not confirmed
    • How MMR factor MutSα signals to block ASF1A-dependent tetrasome deposition mechanistically
  10. 2017 High

    A chaperone-independent function of ASF1a in NHEJ was established: ASF1a interacts with MDC1 to facilitate phospho-ATM docking and downstream RNF8/RNF168 ubiquitination at DSBs, distinguishing its DNA repair role from histone chaperoning.

    Evidence Reciprocal Co-IP of ASF1a–MDC1; siRNA with laser-induced DSB foci; NHEJ reporter; chaperone-dead mutant retaining repair function

    PMID:28943310

    Open questions at the time
    • Structural basis of ASF1a–MDC1 interaction not resolved
    • Phosphorylation event on ASF1a enabling this interaction not yet identified
  11. 2018 High

    USP52 was identified as the deubiquitinase stabilizing ASF1A, and Asf1a was shown to resolve bivalent chromatin domains during ES cell differentiation via nucleosome disassembly at lineage gene promoters, linking ASF1a turnover control and differentiation-specific chromatin dynamics.

    Evidence In vitro DUB assay for USP52; Co-IP; Asf1a KO mouse ES cells with ChIP-seq for bivalent marks; domain mutants separating histone binding from assembly

    PMID:29599486 PMID:29915027

    Open questions at the time
    • Whether USP52 regulation of ASF1a is cell-cycle-dependent
    • How ASF1a is recruited specifically to bivalent promoters
  12. 2021 High

    Identification of Chk1 phosphorylation of ASF1A at Ser-166 downstream of ATM in G1 closed the gap on how ASF1a is activated for its MDC1-dependent NHEJ role, completing the signaling cascade from DSB sensing to histone ubiquitination.

    Evidence In vitro Chk1 kinase assay; phospho-Ser166 antibody; Co-IP of phospho-ASF1A with MDC1; Chk1 inhibitor/KD with NHEJ reporter in G1-synchronized cells

    PMID:33503415

    Open questions at the time
    • Whether additional kinases phosphorylate ASF1A at other sites for repair
    • Structural basis of phospho-Ser166 recognition by MDC1
  13. 2024 High

    ASF1A was shown to act as a P300 cofactor directing site-specific H3K18 lactylation at the SNAI1 promoter, establishing a non-canonical transcriptional regulatory function with in vivo relevance to endothelial-to-mesenchymal transition and atherosclerosis.

    Evidence Co-IP of ASF1A–P300; ChIP for H3K18la at SNAI1; endothelium-specific Asf1a conditional KO in Apoe-null atherosclerosis model

    PMID:39027248

    Open questions at the time
    • Whether ASF1A–P300 co-regulation extends beyond SNAI1 to other lactylation targets
    • Mechanism by which ASF1A directs P300 substrate specificity toward lactylation versus acetylation

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for ASF1A's interaction with MDC1, the genome-wide scope of ASF1A-directed histone lactylation, and how ASF1A's chaperone-dependent and chaperone-independent functions are coordinately regulated across the cell cycle.
  • No structure of ASF1A–MDC1 complex
  • No genome-wide map of ASF1A-dependent H3K18 lactylation
  • Cell-cycle-specific regulation of ASF1A phosphorylation, ubiquitination, and complex partitioning not integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0042393 histone binding 4 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0044183 protein folding chaperone 2
Localization
GO:0005634 nucleus 5 GO:0000228 nuclear chromosome 4 GO:0005654 nucleoplasm 2
Pathway
R-HSA-4839726 Chromatin organization 6 R-HSA-1640170 Cell Cycle 3 R-HSA-73894 DNA Repair 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-69306 DNA Replication 1
Partners
CABIN1EP300HIRAMDC1NASPTAF1UBN1USP52
Complex memberships
CAF-1/ASF1A-H3-H4HUCA (HIRA/UBN1/CABIN1/ASF1a)sNASP-ASF1A-H3-H4

Evidence

Reading pass · 25 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 senescence-associated heterochromatin foci (SAHF) and onset of cellular senescence; ASF1a is required for incorporation of macroH2A and HP1 proteins into SAHF and for senescence-associated cell cycle exit, operating through a pathway that involves flux of heterochromatic proteins through PML nuclear bodies. Co-immunoprecipitation of HIRA-ASF1a complex; siRNA knockdown of ASF1a with SAHF formation and cell cycle exit as phenotypic readouts; immunofluorescence localization to PML bodies Developmental cell High 15621527
2007 Crystal structure (2.7 Å) of CIA-I (ASF1a) in complex with histones H3 and H4 shows that the C-terminal β-strand of histone H4 switches binding partner from histone H2A to ASF1a via a large conformational change; ASF1a has histone H3-H4 tetramer-disrupting activity in vitro, and mutants with weak H3-H4 dimer binding activity show critical functional effects on transcription-related cellular processes. X-ray crystallography; in vitro histone tetramer disruption assay; structure-guided mutagenesis with cellular functional readouts Nature High 17293877
2006 Crystal structure of the human ASF1a-HIRA heterodimer reveals that the HIRA B domain forms an antiparallel β-hairpin that binds perpendicular to the β-sandwich of ASF1a via β-sheet, salt bridge, and van der Waals contacts; the N- and C-terminal regions of ASF1a (but not ASF1b) determine preferential interaction with HIRA; CAF-1 p60 uses a B domain-like motif to compete with HIRA for binding to ASF1a. X-ray crystallography; biochemical competition assays (pull-down, ITC); mutational analysis Nature structural & molecular biology High 16980972
2007 HIRA's translocation to PML nuclear bodies is required for SAHF formation (shown by dominant-negative HIRA mutants and PML-RARα disruption of PML bodies); downstream of PML body localization, the HIRA/ASF1a pathway acts in parallel with pRB to drive SAHF formation, with convergence occurring through the DNAJ-domain protein DNAJA2. Dominant-negative mutants blocking HIRA-PML colocalization; PML-RARα overexpression to disrupt PML bodies; genetic epistasis analysis with pRB and p53 loss-of-function; identification of DNAJA2 as convergence point 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 binds proliferation-promoting genes repressed in senescence, associates with H3K9 methyltransferase activity, and is indispensable for SAHF formation. Co-immunoprecipitation of endogenous complex; recombinant protein binding assays; siRNA knockdown with SAHF formation readout; chromatin immunoprecipitation Molecular and cellular biology High 19029251
2011 CABIN1 is assembled into the quaternary HIRA/UBN1/CABIN1/ASF1a (HUCA) complex via HIRA acting as a scaffold; HIRA interacts with CABIN1 at endogenous levels; CABIN1 is required for heterochromatinization of the senescent genome and co-regulates H3.3-enriched genes together with HIRA in proliferating cells. Endogenous and ectopic Co-immunoprecipitation; reconstitution of quaternary complex from recombinant proteins; mutational analysis of HIRA scaffold function; siRNA knockdown with chromatin phenotype readout Molecular and cellular biology High 21807893
2011 ASF1a is required for post-repair restoration of histone H3K56 acetylation (H3K56Ac) following UV irradiation; restored H3K56Ac is needed for dephosphorylation of γ-H2AX and cellular recovery from checkpoint arrest; H3K56Ac restoration is regulated by ATM checkpoint kinase. siRNA knockdown of ASF1a; quantitative immunoblot of H3K56Ac, γ-H2AX; cell cycle checkpoint recovery assays; ATM inhibition epistasis Nucleic acids research High 21727091
2012 UBN1 residues 41–77 (NHRD) form a tight 1:1 complex (nanomolar Kd) with the WD repeats of HIRA; this interaction is essential for assembly and stability of the HUCA complex in vitro and in vivo; key NHRD residues are required for HIRA interaction and chromatin organization in primary human cells. Analytical ultracentrifugation; mutational analysis; in vitro binding assays; cellular chromatin organization assays Biochemistry High 22401310
2013 ASF1a and ASF1b have undergone subfunctionalization after vertebrate gene duplication; regions outside the primary H3-H4 interaction surface (particularly N- and C-terminal regions carrying signatures of positive selection) determine the preferential interactions of ASF1a versus ASF1b with distinct H3-H4 chaperone complexes. Biochemical binding assays with purified proteins; structural analysis; evolutionary analysis with site-specific signatures of positive selection Molecular biology and evolution Medium 23645555
2014 ASF1a is required for maintenance of pluripotency and somatic cell reprogramming; ASF1a is specifically enriched in the metaphase II human oocyte; overexpression of ASF1a together with OCT4 and oocyte paracrine factor GDF9 is sufficient to reprogram human adult dermal fibroblasts to pluripotent cells. siRNA knockdown of ASF1a in reprogramming assay; ASF1a overexpression with OCT4 and GDF9; pluripotency marker assessment Science Medium 25035411
2014 Upon replication stress (doxorubicin), the ATR checkpoint kinase promotes degradation of ASF1a through the CRL1(βTRCP) ubiquitin-proteasome pathway, leading to dechromatinization and repression of genes overlapping clusters of stalled replication forks. Doxorubicin treatment; proteasome inhibitor rescue; CRL1(βTRCP) knockdown epistasis; ATR inhibition; ChIP for chromatin occupancy; ASF1a protein level assays Genes & development High 24700029
2016 ASF1A-H3-H4 complex participates in CAF-1-dependent histone (H3-H4)₂ tetramer deposition during DNA replication; MutSα (MMR factor) inhibits CAF-1- and ASF1A-H3-H4-dependent packaging of a DNA mismatch into a tetrasome, indicating MMR acts before tetrasome formation; CAF-1/ASF1A-dependent tetramer deposition protects the discontinuous daughter strand from unnecessary degradation by MMR machinery. Reconstituted human in vitro MMR and nucleosome assembly systems; tetrasome assembly assay; strand degradation assays The Journal of biological chemistry High 26945061
2016 sNASP contains at least two additional histone interaction sites beyond the competing TPR-H3 interface that are compatible with ASF1A binding, allowing formation of a quaternary sNASP-ASF1A-H3-H4 complex; sNASP makes a specific complex with H3 alone but not H4, suggesting it acts upstream of ASF1A; together, sNASP and ASF1A can fold an H3-H4 dimer in vitro. Monobody-aided protein interaction mapping; in vitro binding assays; native gel electrophoresis showing quaternary complex; histone folding assay Nucleic acids research High 28123037
2017 ASF1a interacts with MDC1 and is recruited to double-strand break (DSB) sites where it facilitates the interaction of phospho-ATM with MDC1 and ATM-mediated phosphorylation of MDC1; this is required for recruitment of RNF8/RNF168 ubiquitin ligases, histone ubiquitination, 53BP1 recruitment, and NHEJ repair. This role is unique to ASF1a (not ASF1b) and does not require ASF1a's histone chaperone activity. Co-immunoprecipitation of ASF1a-MDC1 interaction; siRNA knockdown with laser-induced DSB foci as readout; NHEJ reporter assay; ATM kinase assay; ASF1a mutants lacking chaperone activity Molecular cell High 28943310
2018 USP52 is a bona fide deubiquitinase that physically associates with ASF1a, promotes its deubiquitination and stabilization, facilitating chromatin assembly and cell cycle progression; impairment of USP52-promoted ASF1a stabilization causes growth arrest and sensitizes breast cancer cells to DNA damage. Co-immunoprecipitation; in vitro deubiquitinase assay; knockdown with cell cycle and DNA damage phenotype readouts Nature communications High 29599486
2018 Asf1a is recruited to bivalent chromatin promoters (partially through association with transcription factors) and mediates nucleosome disassembly required for resolution of bivalent domains and activation of lineage-specific genes during mouse ES cell differentiation; the Asf1a-histone interaction (not its nucleosome assembly role) is required for gene transcription. Asf1a knockout mouse ES cells; ChIP-seq for Asf1a, H3K27me3, H3K4me3; nucleosome disassembly assay; domain mutants separating histone binding from assembly activity Proceedings of the National Academy of Sciences of the United States of America High 29915027
2019 ASF1a inhibition in tumor cells promotes immunogenic M1-like macrophage differentiation in the tumor microenvironment by upregulating GM-CSF expression, potentiating T-cell activation and sensitizing KRAS-mutant lung adenocarcinoma to anti-PD-1 therapy. In vivo CRISPR screen; Asf1a-knockout tumor cells; tumor microenvironment analysis; GM-CSF measurement; macrophage polarization assays; anti-PD-1 combination treatment Cancer discovery Medium 31744829
2019 ASF1a knockdown in wild-type p53-carrying cancer cells induces widespread DNA damage, robust upregulation of p53 and p21cip1 expression, and subsequent cellular senescence; p53 inhibition attenuates p21cip1 induction caused by ASF1a depletion, placing ASF1a upstream of p53-p21cip1 in the senescence pathway. siRNA knockdown; immunoblot for p53/p21; DNA damage markers (γ-H2AX); p53 inhibitor epistasis; SA-β-galactosidase senescence assay Cell death & disease Medium 30692519
2015 The E2 ubiquitin-conjugating enzyme RAD6 cooperates with E3 ligase MDM2 to promote ubiquitination and proteasomal turnover of ASF1A; this RAD6-MDM2 ubiquitin ligase machinery is evolutionarily conserved (demonstrated in Drosophila and human cells). Co-immunoprecipitation in human and Drosophila cells; in vivo ubiquitination assays; MDM2 knockdown/overexpression; proteasome inhibitor rescue Oncotarget Medium 26336826
2021 In G1 phase, Chk1 activated by ATM at DNA double-strand breaks directly phosphorylates ASF1A at Ser-166; phospho-Ser-166 ASF1A interacts with MDC1 and enhances MDC1's interaction with ATM and stable localization of ATM at DSBs; Chk1 deficiency suppresses histone ubiquitination, 53BP1 foci, and NHEJ downstream of MDC1. In vitro kinase assay (Chk1 phosphorylation of ASF1A); phospho-specific antibody; Co-IP of phospho-ASF1A with MDC1; Chk1 inhibitor/knockdown with NHEJ reporter assay; G1 cell cycle synchronization Cell reports High 33503415
2010 Crystal structure (3.3 Å) of CIA/ASF1 in complex with the double bromodomain of CCG1/TAF1 reveals structural basis for their interaction; this interaction is required for colocalization of the two proteins, histone eviction, and RNA polymerase II entry at active promoter regions; the structure provides a mechanistic link between histone acetylation recognition by the bromodomain and ASF1-mediated histone eviction. X-ray crystallography; co-immunoprecipitation; chromatin immunoprecipitation of histone occupancy and Pol II; cellular colocalization assays Proceedings of the National Academy of Sciences of the United States of America High 20393127
2024 ASF1A acts as a cofactor of histone acetyltransferase P300 to precisely regulate enrichment of histone H3K18 lactylation (H3K18la) at the SNAI1 promoter, thereby activating SNAI1 transcription and promoting endothelial-to-mesenchymal transition (EndMT); endothelium-specific deletion of Asf1a inhibits EndMT and alleviates atherosclerosis development in Apoe KO mice. Co-immunoprecipitation of ASF1A-P300 complex; ChIP for H3K18la at SNAI1 promoter; endothelium-specific Asf1a conditional knockout mouse (Apoe KO Asf1a ECKO) atherosclerosis model; PROTAC-mediated protein degradation Acta pharmaceutica Sinica. B High 39027248
2020 Natural product artone directly binds ASF1a and modulates histone H3 post-translational modifications (decreasing acetylation and trimethylation at H3K4, H3K9, H3K18, K27), preventing NF-κB assembly at promoters of pro-inflammatory cytokine genes (Tnf-α, Il-6, Rgs3) in microglia. Direct binding assay (artone-ASF1a interaction); histone PTM mass spectrometry/immunoblot; ChIP for NF-κB at cytokine gene promoters; LPS-activated microglia model Biochemical pharmacology Medium 32222456
2002 Human CIA/ASF1 (hASF1) interacts with the two tandem bromodomain modules of hTAFII250/CCG1, the largest TFIID subunit; yeast Asf1p correspondingly interacts with Bdf1p (the missing bromodomain of yTAFII145); genetic interaction between ASF1 and BDF1 (synthetic lethality of double knockout; suppression of Spt phenotype by TFIID overexpression) establishes functional linkage between the histone chaperone and TFIID. GST pull-down; co-immunoprecipitation; yeast genetic synthetic lethality; Spt phenotype suppression assay Proceedings of the National Academy of Sciences of the United States of America High 12093919
2012 HIRA (but not ASF1a) knockdown significantly reduces p53-mediated induction of large ALT-associated PML bodies and large HP1 foci in ALT cancer cells, demonstrating that HIRA has an ASF1a-independent role in HP1 localization to PML bodies; however, both HIRA and ASF1a colocalize inside PML bodies in normal fibroblasts approaching senescence. siRNA knockdown of HIRA vs. ASF1a; immunofluorescence of HP1, APB, PML body quantification; p53/p21 pathway activation PloS one Medium 21347226

Source papers

Stage 0 corpus · 100 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 554 15621527
2007 Structure and function of the histone chaperone CIA/ASF1 complexed with histones H3 and H4. Nature 248 17293877
1998 B cell-deficient mice do not develop type II collagen-induced arthritis (CIA). Clinical and experimental immunology 245 9528892
2019 In Vivo Epigenetic CRISPR Screen Identifies Asf1a as an Immunotherapeutic Target in Kras-Mutant Lung Adenocarcinoma. Cancer discovery 172 31744829
2006 Structure of a human ASF1a-HIRA complex and insights into specificity of histone chaperone complex assembly. Nature structural & molecular biology 156 16980972
2015 The role of mitochondria and the CIA machinery in the maturation of cytosolic and nuclear iron-sulfur proteins. European journal of cell biology 148 26099175
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
1996 Mucosal tolerance and suppression of collagen-induced arthritis (CIA) induced by nasal inhalation of synthetic peptide 184-198 of bovine type II collagen (CII) expressing a dominant T cell epitope. Clinical and experimental immunology 128 8608633
2020 Urticaria: Collegium Internationale Allergologicum (CIA) Update 2020. International archives of allergy and immunology 121 32224621
2003 The Streptococcus pneumoniae cia regulon: CiaR target sites and transcription profile analysis. Journal of bacteriology 116 12486041
1998 Blockade of IL-12 during the induction of collagen-induced arthritis (CIA) markedly attenuates the severity of the arthritis. Clinical and experimental immunology 114 9486407
1997 Dynamics of proinflammatory cytokine expression in the joints of mice with collagen-induced arthritis (CIA). Clinical and experimental immunology 109 9067525
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
1999 Methotrexate specifically modulates cytokine production by T cells and macrophages in murine collagen-induced arthritis (CIA): a mechanism for methotrexate-mediated immunosuppression. Clinical and experimental immunology 99 9933419
2014 Cancer intelligence acquired (CIA): tumor glycosylation and sialylation codes dismantling antitumor defense. Cellular and molecular life sciences : CMLS 94 25487607
2001 A novel chromatin immunoprecipitation and array (CIA) analysis identifies a 460-kb CENP-A-binding neocentromere DNA. Genome research 90 11230169
2011 Human CABIN1 is a functional member of the human HIRA/UBN1/ASF1a histone H3.3 chaperone complex. Molecular and cellular biology 89 21807893
2010 Cytosolic iron-sulfur cluster assembly (CIA) system: factors, mechanism, and relevance to cellular iron regulation. The Journal of biological chemistry 84 20522543
2019 The Cellular Functions of Eosinophils: Collegium Internationale Allergologicum (CIA) Update 2020. International archives of allergy and immunology 83 31786573
2024 ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT. Acta pharmaceutica Sinica. B 74 39027248
2014 Cell reprogramming. Histone chaperone ASF1A is required for maintenance of pluripotency and cellular reprogramming. Science (New York, N.Y.) 68 25035411
2004 TIP30 interacts with an estrogen receptor alpha-interacting coactivator CIA and regulates c-myc transcription. The Journal of biological chemistry 67 15073177
1997 Cytokine production in synovial tissue of mice with collagen-induced arthritis (CIA). Clinical and experimental immunology 67 9067522
2001 CIA, a novel estrogen receptor coactivator with a bifunctional nuclear receptor interacting determinant. Molecular and cellular biology 66 11113208
1999 Effects of bucillamine and N-acetyl-L-cysteine on cytokine production and collagen-induced arthritis (CIA). Clinical and experimental immunology 66 9933417
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.) 65 31914881
2006 Imatinib mesylate inhibits osteoclastogenesis and joint destruction in rats with collagen-induced arthritis (CIA). Journal of bone and mineral metabolism 60 16816921
2011 ASF1A and ATM regulate H3K56-mediated cell-cycle checkpoint recovery in response to UV irradiation. Nucleic acids research 59 21727091
2000 Intra-articular IL-10 gene transfer regulates the expression of collagen-induced arthritis (CIA) in the knee and ipsilateral paw. Clinical and experimental immunology 57 10792391
1999 CD44 involvement in experimental collagen-induced arthritis (CIA). Journal of autoimmunity 56 10441166
2013 Subfunctionalization via adaptive evolution influenced by genomic context: the case of histone chaperones ASF1a and ASF1b. Molecular biology and evolution 54 23645555
2002 Identification and characterization of CIA/ASF1 as an interactor of bromodomains associated with TFIID. Proceedings of the National Academy of Sciences of the United States of America 53 12093919
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
2015 Mangiferin suppresses CIA by suppressing the expression of TNF-α, IL-6, IL-1β, and RANKL through inhibiting the activation of NF-κB and ERK1/2. American journal of translational research 50 26396668
1999 Anti-inflammatory effects of a new tumour necrosis factor-alpha (TNF-alpha) inhibitor (CNI-1493) in collagen-induced arthritis (CIA) in rats. Clinical and experimental immunology 46 9933418
2021 Circular RNA cia-MAF drives self-renewal and metastasis of liver tumor-initiating cells via transcription factor MAFF. The Journal of clinical investigation 43 34403373
2019 Pharmacological inhibition of TAK1, with the selective inhibitor takinib, alleviates clinical manifestation of arthritis in CIA mice. Arthritis research & therapy 43 31847895
2001 Leaf-specific upregulation of chloroplast translocon genes by a CCT motif-containing protein, CIA 2. The Plant cell 42 11549763
2018 USP52 acts as a deubiquitinase and promotes histone chaperone ASF1A stabilization. Nature communications 40 29599486
1999 Encapsulation in hollow fibres of xenogeneic cells engineered to secrete IL-4 or IL-13 ameliorates murine collagen-induced arthritis (CIA). Clinical and experimental immunology 40 10444273
2020 Pathogenesis and Therapy of Primary Cutaneous T-Cell Lymphoma: Collegium Internationale Allergologicum (CIA) Update 2020. International archives of allergy and immunology 39 32690848
2012 Transcriptional profiling of human familial longevity indicates a role for ASF1A and IL7R. PloS one 39 22247756
2009 Crucial role of conserved cysteine residues in the assembly of two iron-sulfur clusters on the CIA protein Nar1. Biochemistry 39 19385603
2023 Tubson-2 decoction ameliorates rheumatoid arthritis complicated with osteoporosis in CIA rats involving isochlorogenic acid A regulating IL-17/MAPK pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 38 37263000
2008 The cia operon of Streptococcus mutans encodes a unique component required for calcium-mediated autoregulation. Molecular microbiology 38 18681938
2001 Prophylactic and therapeutic effects of a humanized monoclonal antibody against the IL-2 receptor (DACLIZUMAB) on collagen-induced arthritis (CIA) in rhesus monkeys. Clinical and experimental immunology 37 11359452
2017 ASF1a Promotes Non-homologous End Joining Repair by Facilitating Phosphorylation of MDC1 by ATM at Double-Strand Breaks. Molecular cell 35 28943310
2013 IOP1 protein is an external component of the human cytosolic iron-sulfur cluster assembly (CIA) machinery and functions in the MMS19 protein-dependent CIA pathway. The Journal of biological chemistry 35 23585563
2019 Lobe-Specific Lymph Node Dissection for Clinical Early-Stage (cIA) Peripheral Non-small Cell Lung Cancer Patients: What and How? Annals of surgical oncology 34 31617120
2019 An Oxygen-Dependent Interaction between FBXL5 and the CIA-Targeting Complex Regulates Iron Homeostasis. Molecular cell 33 31229404
2012 Incidence and predictors of ovarian function recovery (OFR) in breast cancer (BC) patients with chemotherapy-induced amenorrhea (CIA) who switched from tamoxifen to exemestane. Annals of oncology : official journal of the European Society for Medical Oncology 33 23108951
2005 B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model. Blood 33 15947095
2020 Structural insights into Fe-S protein biogenesis by the CIA targeting complex. Nature structural & molecular biology 31 32632277
2019 Atopic Dermatitis: Collegium Internationale Allergologicum (CIA) Update 2019. International archives of allergy and immunology 31 30739107
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 30 22401310
2003 Transcription initiation factor IID-interactive histone chaperone CIA-II implicated in mammalian spermatogenesis. The Journal of biological chemistry 30 12842904
2007 The nuclear PP1 interacting protein ZAP3 (ZAP) is a putative nucleoside kinase that complexes with SAM68, CIA, NF110/45, and HNRNP-G. Biochimica et biophysica acta 29 17890166
2019 ASF1a inhibition induces p53-dependent growth arrest and senescence of cancer cells. Cell death & disease 28 30692519
2017 The CIA Targeting Complex Is Highly Regulated and Provides Two Distinct Binding Sites for Client Iron-Sulfur Proteins. Cell reports 28 28178521
2016 DNA Mismatch Repair Interacts with CAF-1- and ASF1A-H3-H4-dependent Histone (H3-H4)2 Tetramer Deposition. The Journal of biological chemistry 28 26945061
1993 Depletion of CD4+ and CD8+ T lymphocyte subpopulations by CIA-1, a chicken infectious anemia virus. Avian diseases 27 8363513
2019 Naltrexone (NTX) relieves inflammation in the collagen-induced- arthritis (CIA) rat models through regulating TLR4/NFκB signaling pathway. International immunopharmacology 26 31865244
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 26 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
2020 IgD-Fc-Ig fusion protein, a new biological agent, inhibits T cell function in CIA rats by inhibiting IgD-IgDR-Lck-NF-κB signaling pathways. Acta pharmacologica Sinica 24 31937932
2016 Relationship between PI3K pathway and angiogenesis in CIA rat synovium. American journal of translational research 24 27508035
2011 Characterization of CIA-1, an Ambler class A extended-spectrum β-lactamase from Chryseobacterium indologenes. Antimicrobial agents and chemotherapy 23 22083470
1965 THE MECHANISM OF 5-AMINOURACIL-INDUCED SYNCHRONY OF CELL DIVISION IN VI CIA FABA ROOT MERISTEMS. The Journal of cell biology 23 19866644
2016 Treatment of CIA Mice with FGF21 Down-regulates TH17-IL-17 Axis. Inflammation 22 26424095
2016 sNASP and ASF1A function through both competitive and compatible modes of histone binding. Nucleic acids research 22 28123037
2014 The study of mechanisms of protective effect of Rg1 against arthritis by inhibiting osteoclast differentiation and maturation in CIA mice. Mediators of inflammation 21 25214714
2010 Structure of the histone chaperone CIA/ASF1-double bromodomain complex linking histone modifications and site-specific histone eviction. Proceedings of the National Academy of Sciences of the United States of America 21 20393127
1999 Secretion of Campylobacter jejuni Cia proteins is contact dependent. Advances in experimental medicine and biology 21 10659362
2023 Panax notoginseng saponins (PNS) attenuate Th17 cell differentiation in CIA mice via inhibition of nuclear PKM2-mediated STAT3 phosphorylation. Pharmaceutical biology 20 36794740
2018 Synthesis, Structure and Biological Activity of CIA and CIB, Two α-Conotoxins from the Predation-Evoked Venom of Conus catus. Toxins 20 29857567
2018 Comparative Studies of Different Extracts from Eucommia ulmoides Oliv. against Rheumatoid Arthritis in CIA Rats. Evidence-based complementary and alternative medicine : eCAM 20 30105062
2019 Effects of daphnetin on the autophagy signaling pathway of fibroblast-like synoviocytes in rats with collagen-induced arthritis (CIA) induced by TNF-α. Cytokine 19 31865066
1997 Prevention of collagen-induced arthritis (CIA) by treatment with polyethylene glycol-conjugated type II collagen; distinct tolerogenic property of the conjugated collagen from the native one. Clinical and experimental immunology 18 9158088
2020 Hepatocyte growth factor overexpression promotes osteoclastogenesis and exacerbates bone loss in CIA mice. Journal of orthopaedic translation 17 33344167
2013 Identification of early HIV infections using the fourth generation Abbott ARCHITECT HIV Ag/Ab Combo chemiluminescent microparticle immunoassay (CIA) in San Diego County. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology 17 24342477
2019 Anti-Arthritis Effect through the Anti-Inflammatory Effect of Sargassum muticum Extract in Collagen-Induced Arthritic (CIA) Mice. Molecules (Basel, Switzerland) 16 30642121
2024 Wutou decoction alleviates arthritis inflammation in CIA mice by regulating Treg cell stability and Treg/Th17 balance via the JAK2/STAT3 pathway. Journal of ethnopharmacology 15 38908493
2022 Berberis lycium fruit extract and its phytoconstituents berberine and rutin mitigate collagen-CFA-induced arthritis (CIA) via improving GSK3β/STAT/Akt/MAPKs/NF-κB signaling axis mediated oxi-inflammation and joint articular damage in murine model. Inflammopharmacology 15 35254584
1997 Characteristics of synovial fluid effusion in collagen-induced arthritis (CIA) in the DA rat; a comparison of histology and antibody reactivities in an experimental chronic arthritis model and rheumatoid arthritis (RA). Clinical and experimental immunology 15 9067521
2015 A conserved RAD6-MDM2 ubiquitin ligase machinery targets histone chaperone ASF1A in tumorigenesis. Oncotarget 14 26336826
2021 SZAP exerts analgesic effects on rheumatalgia in CIA rats by suppressing pain hyperalgesia and inhibiting TRPV1 and P2X3. Journal of ethnopharmacology 13 34728318
2015 DC-Based Immunotherapy Combined with Low-Dose Methotrexate Effective in the Treatment of Advanced CIA in Mice. Journal of immunology research 13 26221616
2023 Maintenance of genome integrity by the late-acting cytoplasmic iron-sulfur assembly (CIA) complex. Frontiers in genetics 12 36968611
2021 Chk1 promotes non-homologous end joining in G1 through direct phosphorylation of ASF1A. Cell reports 12 33503415
2021 IgD promotes pannus formation by activating Wnt5A-Fzd5-CTHRC1-NF-κB signaling pathway in FLS of CIA rats and the regulation of IgD-Fc-Ig fusion protein. International immunopharmacology 12 34688134
2019 Amelioration of CIA by Asarinin Is Associated to a Downregulation of TLR9/NF-κB and Regulation of Th1/Th2/Treg Expression. Biological & pharmaceutical bulletin 12 31019160
2019 Systemic Resolvin E1 (RvE1) Treatment Does Not Ameliorate the Severity of Collagen-Induced Arthritis (CIA) in Mice: A Randomized, Prospective, and Controlled Proof of Concept Study. Mediators of inflammation 12 31780864
2018 Streptococcus sanguinis Noncoding cia-Dependent Small RNAs Negatively Regulate Expression of Type IV Pilus Retraction ATPase PilT and Biofilm Formation. Infection and immunity 12 29263111
2020 Small-molecule arone protects from neuroinflammation in LPS-activated microglia BV-2 cells by targeting histone-remodeling chaperone ASF1a. Biochemical pharmacology 11 32222456
2020 Paeoniflorin-6'-o-benzene sulfonate (CP-25) improves vasculitis through inhibiting IL-17A/JAK/STAT3 signaling pathway in endothelial cells of HFD CIA rats. Phytotherapy research : PTR 11 33006176
2019 Flemingia philippinensis Flavonoids Relieve Bone Erosion and Inflammatory Mediators in CIA Mice by Downregulating NF-κB and MAPK Pathways. Mediators of inflammation 11 30906224
2018 Toll-Like Receptor 4-Myeloid Differentiation Primary Response Gene 88 Pathway Is Involved in the Shikonin Treatment of CIA by Regulating Treg/Th17 Expression. Evidence-based complementary and alternative medicine : eCAM 11 30643526
2010 Amebic monocyte locomotion inhibitory factor peptide ameliorates inflammation in CIA mouse model by downregulation of cell adhesion, inflammation/chemotaxis, and matrix metalloproteinases genes. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 11 20582714