Affinage

CHAF1B

Chromatin assembly factor 1 subunit B · UniProt Q13112

Length
559 aa
Mass
61.5 kDa
Annotated
2026-06-09
23 papers in source corpus 13 papers cited in narrative 12 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CHAF1B is the medium (p60) subunit of the trimeric CAF-1 histone chaperone complex, a WD-repeat protein that shuttles newly synthesized histone H3/H4 to the replication fork to drive replication-coupled chromatin assembly (PMID:26066981). In mouse preimplantation embryos it mediates replacement of histone H3.3 with H3.1/H3.2, establishing repressive chromatin (gained H3K9me2/3 and H3K27me2/3, lost H3K4me2/3) and supporting expression of pluripotency factors, with its loss causing apoptosis and post-implantation lethality (PMID:34906611). Beyond canonical chromatin assembly, CHAF1B operates as a transcriptional repressor by binding directly to target promoters such as TRIM13 and SETD7 to silence them, configuring oncogenic programs in AML and lung squamous-cell carcinoma; in the leukemic context this defines a CHAF1B→TRIM13→CCNA1 cell-cycle axis (PMID:37205848, PMID:39862337). In germinal center B cells CHAF1B associates with BCL6 and TBL1XR1 and stabilizes this co-repressor complex to support GC organization, B cell differentiation, and high-affinity antibody responses (PMID:41764732). CHAF1B additionally functions as an E3 ubiquitin ligase that ubiquitinates and degrades the nuclear co-repressor NCOR2 (PMID:32508530), and it promotes DNA-PK–dependent DNA damage repair and radioresistance (PMID:31869663). Across multiple cancers CHAF1B supports proliferation, invasion, and therapy resistance and modulates immune signaling, including a nuclear interaction with ULK1 that restrains IFNα-stimulated gene transcription (PMID:37377894) and IL-33–driven microglial polarization in glioma (PMID:41102004).

Mechanistic history

Synthesis pass · year-by-year structured walk · 9 steps
  1. 1996 Medium

    Establishing the gene's chromosomal location and complex membership was the first step in defining CHAF1B as a histone-assembly factor of potential developmental relevance.

    Evidence FISH, somatic cell hybrids, and YAC/cosmid mapping placing CAF1P60 at 21q22.2 within the Down syndrome critical region

    PMID:8660983 PMID:8792829

    Open questions at the time
    • Functional role inferred from prior literature, not new experiment
    • No mechanistic link between map position and Down syndrome phenotype established
  2. 2015 Medium

    Consolidation of CAF-1 biochemistry defined CHAF1B's domain architecture and its role as the p60 subunit chaperoning H3/H4 to the replication fork.

    Evidence Review/synthesis of prior CAF-1 complex biochemistry describing 7× WD-repeat, B-like, and PEST domains

    PMID:26066981

    Open questions at the time
    • No single new experiment; relies on prior studies
    • Does not address non-replicative functions
  3. 2021 Medium

    Linking CHAF1B to histone variant exchange showed how its chaperone activity translates into a defined chromatin state and developmental outcome.

    Evidence siRNA knockdown in mouse embryos with RNA-seq, ATAC-seq, and histone mark Western blots showing H3.3→H3.1/H3.2 replacement and repressive-mark gain

    PMID:34906611

    Open questions at the time
    • Mechanism of variant selection not resolved
    • Single lab; not extended to other developmental contexts
  4. 2020 Medium

    Identification of E3 ubiquitin ligase activity toward NCOR2 revealed a chromatin-independent post-translational function for CHAF1B.

    Evidence Proteome microarray, Co-IP, and ubiquitination assay in lung adenocarcinoma showing nuclear CHAF1B–NCOR2 interaction and NCOR2 degradation

    PMID:32508530

    Open questions at the time
    • No structural basis for ligase activity defined
    • WD-repeat protein acting as E3 not reconstituted in vitro
    • Single lab
  5. 2019 Medium

    Placing CHAF1B in the DNA-PK repair pathway connected it to genome maintenance and therapy resistance beyond replication.

    Evidence Loss/gain-of-function with γH2AX foci resolution and DNA-PK inhibitor sensitization in nasopharyngeal carcinoma plus xenografts

    PMID:31869663

    Open questions at the time
    • Direct molecular interaction with DNA-PK components not shown
    • Single lab
  6. 2023 Medium

    Demonstration of direct promoter binding (TRIM13) established CHAF1B as a sequence-targeted transcriptional repressor driving a leukemogenic cell-cycle axis.

    Evidence ChIP for CHAF1B promoter binding plus functional epistasis (TRIM13→CCNA1) in AML lines and patient-derived xenografts

    PMID:37205848

    Open questions at the time
    • How CHAF1B is recruited to specific promoters unknown
    • Repressive complex partners at TRIM13 not defined
  7. 2023 Medium

    A nuclear CHAF1B–ULK1 interaction linked the chaperone to control of interferon-stimulated gene transcription in myeloproliferative neoplasms.

    Evidence Co-IP interaction studies and shRNA silencing with gene expression and primary MPN progenitor assays

    PMID:37377894

    Open questions at the time
    • Reciprocal validation and stoichiometry of ULK1 interaction not established
    • Direct transcriptional mechanism at ISGs unclear
  8. 2025 High

    A second direct promoter target (SETD7) and identification of the BCL6/TBL1XR1 co-repressor complex generalized CHAF1B's repressor role across tumor and immune contexts.

    Evidence ChIP at SETD7 in lung squamous carcinoma; Co-IP/MS plus conditional knockout mice for BCL6/TBL1XR1 in germinal center B cells

    PMID:39862337 PMID:41764732

    Open questions at the time
    • Whether promoter targeting and complex stabilization use a shared molecular mechanism unresolved
    • Determinants of target-gene selection unknown
  9. 2025 Low

    Functional studies placed CHAF1B upstream of PI3K/Akt and IL-33 immune-signaling axes, broadening its role into tumor microenvironment modulation.

    Evidence RNA-seq with pathway inhibitors in HCC (PI3K/Akt/HIF-1α) and IL-33 neutralization with intracranial xenografts in glioma stem cells

    PMID:41049428 PMID:41102004

    Open questions at the time
    • HCC pathway placement rests on pharmacological inhibition only, no direct binding or reconstitution
    • Direct molecular link between CHAF1B and IL-33 secretion not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single WD-repeat chaperone subunit mechanistically unifies replication-coupled histone deposition, sequence-specific promoter repression, and E3 ligase activity remains unresolved.
  • No structural model reconciling chaperone, repressor, and ligase functions
  • Mechanism of promoter recruitment unidentified
  • Whether non-canonical functions require the full CAF-1 complex untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 2 GO:0016874 ligase activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 3 GO:0000228 nuclear chromosome 2
Pathway
R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-4839726 Chromatin organization 2 R-HSA-73894 DNA Repair 1
Complex memberships
BCL6/TBL1XR1 co-repressor complexCAF-1

Evidence

Reading pass · 12 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 The CHAF1B (CAF1P60/CAF1A) gene was mapped to human chromosome 21q22.2, within the Down syndrome critical region, and encodes the p60 subunit of the CAF-1 complex that interacts with other subunits to promote histone assembly onto replicating DNA. Fluorescence in situ hybridization, somatic cell hybrids, YAC/cosmid hybridization, exon trapping Human genetics / Genomics Medium 8660983 8792829
2015 CHAF1B is the medium (p60) subunit of the trimeric CAF-1 complex and contains a 7× WD repeat domain, a B-like domain, and a PEST domain; it functions as a histone H3/H4 chaperone shuttling newly synthesized histones to the replication fork during DNA synthesis. Review/synthesis of prior experimental literature on CAF-1 complex biochemistry Biochimica et biophysica acta Medium 26066981
2018 Knockdown of CHAF1B in hepatocellular carcinoma (HUH-7) cells reduced invasion and migration ability, induced S-phase accumulation, and inhibited tumor growth in vivo; downstream gene expression changes included upregulation of PSMB6, SLC30A7, and SMC3, and downregulation of BLM and TWF2. Lentiviral shRNA knockdown, scratch wound healing assay, Transwell invasion assay, flow cytometry, gene expression profiling, Western blot, RT-PCR, xenograft mouse model Oncology reports Medium 29767268
2019 CHAF1B promotes DNA damage repair in nasopharyngeal carcinoma cells following radiation, inhibiting apoptosis and conferring radioresistance; this mechanism is dependent on the DNA-PK pathway, as demonstrated by γH2AX foci resolution and DNA-PK inhibitor sensitization. siRNA/shRNA knockdown and overexpression, colony formation assay, γH2AX foci detection, flow cytometry (apoptosis), MTT assay, xenograft model, DNA-PK inhibitor treatment Biomedicine & pharmacotherapy Medium 31869663
2020 CHAF1B acts as an E3 ubiquitin ligase that promotes ubiquitination and degradation of the nuclear co-repressor NCOR2; CHAF1B and NCOR2 physically interact predominantly in the nucleus, and CHAF1B-mediated NCOR2 degradation drives cisplatin resistance in lung adenocarcinoma. Proteome microarray, Western blot, co-immunoprecipitation, qRT-PCR, cell proliferation/migration assays, apoptosis assay, xenograft mouse model, immunohistochemistry, ubiquitination assay Cancer cell international Medium 32508530
2021 CHAF1B depletion in mouse preimplantation embryos increases apoptosis, reduces blastocyst hatching and outgrowth, causes embryonic lethality post-implantation, and decreases expression of pluripotency factors (Oct4, Cdx2, Sox2, Nanog). Mechanistically, CHAF1B mediates replacement of histone H3.3 with H3.1/H3.2, associated with increased repressive marks (H3K9me2/3, H3K27me2/3) and decreased active marks (H3K4me2/3). siRNA knockdown in embryos, immunofluorescence, flow cytometry (apoptosis), RNA-sequencing, ATAC-sequencing, Western blot International journal of biological macromolecules Medium 34906611
2023 CHAF1B binds directly to the TRIM13 promoter to repress its transcription in AML cells; loss of CHAF1B de-represses TRIM13, which then ubiquitinates CCNA1 to promote cell cycle entry and ultimately leukemic cell exhaustion, identifying the CHAF1B→TRIM13→CCNA1 axis as a key leukemogenic pathway. RNA sequencing, ChIP (CHAF1B promoter binding), knockdown/overexpression in AML cell lines and patient-derived xenografts, cell cycle and self-renewal assays Blood advances Medium 37205848
2023 CHAF1B interacts with ULK1 (Unc-51-like kinase 1) in the nuclear compartment of MPN cells; silencing CHAF1B enhances transcription of IFNα-stimulated genes and potentiates IFNα-dependent antineoplastic responses in primary MPN progenitor cells. Co-immunoprecipitation/interaction studies, shRNA silencing, gene expression analysis, primary MPN progenitor cell functional assays Cancer research communications Medium 37377894
2025 CHAF1B competitively binds to the SETD7 promoter region and represses its transcription in lung squamous-cell carcinoma, promoting cell proliferation; silencing CHAF1B upregulates SETD7 and suppresses tumor growth in vitro and in vivo. WGCNA bioinformatics, ChIP (promoter binding), CHAF1B knockdown, RNA sequencing, in vitro proliferation assays, xenograft model Frontiers of medicine Medium 39862337
2025 CHAF1B promotes malignant phenotypes in hepatocellular carcinoma via activation of the PI3K/Akt/HIF-1α pathway; blockade of this pathway partially attenuates CHAF1B-mediated sorafenib resistance, placing CHAF1B upstream of PI3K/Akt/HIF-1α. RNA sequencing, pathway-specific inhibitors, siRNA knockdown, CCK8, colony formation, Transwell migration/invasion, flow cytometry, Western blot International journal of medical sciences Low 41049428
2025 CHAF1B physically associates with BCL6 and TBL1XR1 in germinal center B cells (identified by Co-IP/MS); CHAF1B stabilizes the BCL6/TBL1XR1 repressor complex to cooperatively repress transcription, promote GC dark zone/light zone organization, and support GC B cell differentiation and antibody production. Loss of CHAF1B impairs GC formation, induces apoptosis, and reduces high-affinity antibody responses. Co-immunoprecipitation coupled with mass spectrometry, conditional knockout mouse models, flow cytometry, immunofluorescence, transcriptional reporter assays Journal of immunology High 41764732
2025 Chaf1b upregulates IL-33 secretion in glioma stem cells, promoting microglial M2 polarization and activating the PI3K/AKT signaling pathway; neutralization of IL-33 reverses these effects, placing Chaf1b upstream of IL-33–PI3K/AKT in the GBM stem-immune axis. Genetic silencing in patient-derived GSCs, intracranial xenograft models, IL-33 neutralization, flow cytometry, self-renewal and tumorigenicity assays The Journal of neuroscience Medium 41102004

Source papers

Stage 0 corpus · 23 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 The anti-proliferative activity of BTG/TOB proteins is mediated via the Caf1a (CNOT7) and Caf1b (CNOT8) deadenylase subunits of the Ccr4-not complex. PloS one 64 23236473
1995 Specific high affinity binding of human interleukin 1 beta by Caf1A usher protein of Yersinia pestis. FEBS letters 51 7664886
2015 The role of the chromatin assembly complex (CAF-1) and its p60 subunit (CHAF1b) in homeostasis and disease. Biochimica et biophysica acta 48 26066981
2018 CHAF1B knockdown blocks migration in a hepatocellular carcinoma model. Oncology reports 22 29767268
2022 Long non-coding RNA lnc-CHAF1B-3 promotes renal interstitial fibrosis by regulating EMT-related genes in renal proximal tubular cells. Molecular therapy. Nucleic acids 18 36700051
2019 CHAF1B induces radioresistance by promoting DNA damage repair in nasopharyngeal carcinoma. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 31869663
2009 Caf1A usher possesses a Caf1 subunit-like domain that is crucial for Caf1 fibre secretion. The Biochemical journal 16 19032149
1996 The gene encoding the p60 subunit of chromatin assembly factor I (CAF1P60) maps to human chromosome 21q22.2, a region associated with some of the major features of Down syndrome. Human genetics 14 8792829
2010 Conserved hydrophobic clusters on the surface of the Caf1A usher C-terminal domain are important for F1 antigen assembly. Journal of molecular biology 12 20797400
2020 Ubiquitin ligase CHAF1B induces cisplatin resistance in lung adenocarcinoma by promoting NCOR2 degradation. Cancer cell international 10 32508530
1996 Mapping of the gene for the p60 subunit of the human chromatin assembly factor (CAF1A) to the Down syndrome region of chromosome 21. Genomics 10 8660983
2023 Repression of TRIM13 by chromatin assembly factor CHAF1B is critical for AML development. Blood advances 9 37205848
2022 Circ_0026134 promotes NSCLC progression by the miR-3619-5p/CHAF1B axis. Thoracic cancer 8 34985193
2023 Targeting CHAF1B Enhances IFN Activity against Myeloproliferative Neoplasm Cells. Cancer research communications 6 37377894
2021 CHAF1b, chromatin assembly factor-1 subunit b, is essential for mouse preimplantation embryos. International journal of biological macromolecules 6 34906611
2021 Detection of CAF-1/p60 in peripheral blood as a potential biomarker of HNSCC tumors. Oral oncology 4 34237585
2018 CHAF1B Overexpression: A Brake for the Differentiation of Leukemia Cells. Cancer cell 4 30423290
2025 CHAF1B promotes the progression of lung squamous-cell carcinoma by inhibiting SETD7 expression. Frontiers of medicine 2 39862337
2025 Integrated bioinformatics and experimental analysis of CHAF1B as a novel biomarker and immunotherapy target in LUAD. Discover oncology 1 39806171
2026 Histone chaperone CHAF1B facilitates germinal center B cell differentiation via cooperation with BCL6 and TBL1XR1. Journal of immunology (Baltimore, Md. : 1950) 0 41764732
2025 lncRNA CHAF1B-2 contributes to the tumorigenesis of gastric cancer by activating the Wnt/β-catenin pathway. Scientific reports 0 39747989
2025 CHAF1B: the hidden culprit behind sorafenib resistance in hepatocellular carcinoma. International journal of medical sciences 0 41049428
2025 The Role of Chaf1b in Maintaining Glioma Stem Cell Stemness and Regulating Microglial Polarization. The Journal of neuroscience : the official journal of the Society for Neuroscience 0 41102004

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