Affinage

HCFC1

Host cell factor 1 · UniProt P51610

Length
2035 aa
Mass
208.7 kDa
Annotated
2026-04-28
100 papers in source corpus 44 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HCFC1 (HCF-1) is a large chromatin-associated transcriptional co-regulator that scaffolds opposing histone-modifying complexes to control cell proliferation, cytokinesis, and metabolic gene expression. The HCF-1N subunit, generated by OGT-mediated proteolytic cleavage at HCF-1PRO repeats within the OGT active site, uses its Kelch/β-propeller domain to tether Set1/MLL H3K4 methyltransferase and Sin3-HDAC complexes to sequence-specific transcription factors — including E2F1, THAP11, ZNF143, and VP16 — at thousands of CpG-island promoters, thereby driving G1-to-S progression and context-dependent gene activation or repression (PMID:12670868, PMID:17612494, PMID:23539139). The HCF-1C subunit ensures proper cytokinesis by regulating PR-Set7 expression and mitotic H4-K20 methylation, and the noncovalently associated subunits are held together by interdigitated Fn3 self-association sequences that also recruit the nuclear localization signal (PMID:12743030, PMID:15200950, PMID:23045687). Missense mutations in the HCFC1 Kelch domain cause the X-linked cblX disorder through transcriptional failure at the MMACHC promoter, and HCFC1/THAP11 mutations additionally impair ribosome biogenesis gene expression (PMID:24011988, PMID:35013307).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2000 High

    Defining how HCF-1N and HCF-1C subunits remain associated and reach the nucleus resolved the basic architecture of the processed heterodimer: matched self-association sequences (SAS1/SAS2) mediate inter-subunit binding, and the HCF-1C NLS drives nuclear import of both subunits.

    Evidence Co-immunoprecipitation and deletion mutagenesis with subcellular localization assays

    PMID:10958670

    Open questions at the time
    • Structural basis of SAS interactions unknown at this point
    • Whether SAS mutations affect endogenous HCF-1 function in vivo not tested
  2. 2001 High

    Demonstrating that HCF-1 is constitutively chromatin-bound in uninfected cells — and that loss of chromatin association precedes the tsBN67 proliferation arrest — established chromatin association as essential for HCF-1's proliferative function, independent of any viral context.

    Evidence Chromatin fractionation and temperature-shift experiments in tsBN67 cells

    PMID:11340173

    Open questions at the time
    • Identity of chromatin targets unknown
    • Mechanism of chromatin recruitment unresolved
  3. 2002 Medium

    Epistasis experiments placing HCF-1 upstream of pRb family function, identification of the HCF-1C activation domain required for VP16/LZIP-mediated transcription, discovery of HPIP as a nuclear-export factor for HCF-1, involvement of HCF-1 in spliceosome assembly, and identification of PDCD2 as a negative regulator collectively defined HCF-1 as a multifunctional nuclear regulator with roles beyond viral transactivation.

    Evidence Genetic rescue by pRb-inactivating oncoproteins, reporter assays with HCF-1AD mutants, HSV infection assays, co-IP with snRNPs, in vitro splicing, co-IP with PDCD2 and HPIP

    PMID:12149646 PMID:12215534 PMID:12235138 PMID:12271126 PMID:12456665

    Open questions at the time
    • Splicing role not confirmed by independent labs
    • Whether HPIP-mediated cytoplasmic relocalization is physiologically regulated unknown
    • Direct pRb interaction not demonstrated
  4. 2003 High

    Two foundational discoveries established that HCF-1 proteolytic processing separates distinct cell-cycle functions (HCF-1N for G1 progression, HCF-1C for cytokinesis) and that HCF-1 scaffolds antagonistic chromatin-modifying complexes (Set1/Ash2 HMT and Sin3 HDAC) on the same molecule, with VP16 selectively engaging the HMT-associated form.

    Evidence siRNA knockdown with subunit rescue, co-IP/mass spectrometry with histone methyltransferase activity assays

    PMID:12670868 PMID:12743030

    Open questions at the time
    • How selectivity between HMT and HDAC complexes is achieved at specific promoters unknown
    • Identity of endogenous transcription factors directing complex selection unclear
  5. 2004 High

    HCF-1C was shown to control mitotic H4-K20 methylation by regulating PR-Set7 expression, explaining the cytokinesis defect: HCF-1 loss upregulates PR-Set7, causing aberrant dimethylation of H4-K20 and defective chromosome segregation.

    Evidence siRNA knockdown, quantitative ChIP, chromatin fractionation, immunofluorescence

    PMID:15200950

    Open questions at the time
    • Direct transcriptional mechanism by which HCF-1C represses PR-Set7 not established
    • Whether other H4-K20 methyltransferases are involved not tested
  6. 2007 High

    Linking HCF-1 to cell-cycle-regulated E2F proteins resolved how HCF-1 activates endogenous G1/S gene expression: HCF-1 associates selectively with activator E2Fs during G1-to-S transition and recruits MLL/Set1 to E2F-responsive promoters for H3K4 methylation.

    Evidence Co-IP, ChIP, reporter assays with cell-cycle synchronization

    PMID:17612494

    Open questions at the time
    • How HCF-1 switches from repressor E2F4 to activator E2F1 complexes not mechanistically resolved
    • Whether HCF-1-E2F interaction is direct or bridged unknown
  7. 2008 High

    Two parallel advances expanded HCF-1 biology: in C. elegans, HCF-1 was found to physically restrain DAF-16/FOXO at target promoters such that hcf-1 loss extends lifespan; in sensory neurons, HCF-1 was found sequestered at the Golgi apparatus, with Golgi disruption releasing it to the nucleus — a mechanism controlling HSV reactivation.

    Evidence Co-IP and ChIP with genetic epistasis and lifespan assays (C. elegans); immunofluorescence and Golgi disruption in primary neurons

    PMID:18667495 PMID:18828672

    Open questions at the time
    • Mechanism of Golgi tethering unknown
    • Whether mammalian FOXO factors are similarly regulated by HCF-1 in longevity not demonstrated in vivo
  8. 2009 High

    BAP1 deubiquitinase was identified as removing K48-linked polyubiquitin from the HCF-1N Kelch domain, linking HCF-1 to tumor-suppressor pathways; separately, the E2F1–HCF-1 interaction was shown to channel E2F1 activity toward apoptosis via MLL recruitment.

    Evidence Mass spectrometry, ubiquitination assays, co-IP (BAP1); mutagenesis of E2F1 HBM with apoptosis assays

    PMID:19763085 PMID:19815555

    Open questions at the time
    • Whether BAP1-mediated deubiquitination stabilizes HCF-1 or alters its interactions not fully resolved
    • Mechanism distinguishing E2F1 apoptotic versus proliferative outputs unclear
  9. 2010 High

    Genome-wide studies with THAP11 (Ronin) and THAP1 established HCF-1 as a broadly acting transcriptional scaffold recruited by zinc-finger/THAP-domain proteins to regulate ES cell self-renewal and endothelial proliferation genes.

    Evidence ChIP-seq, co-IP, gene expression profiling, RNAi in ES cells and endothelial cells

    PMID:20200153 PMID:20581084

    Open questions at the time
    • Whether THAP11 and THAP1 compete or cooperate for HCF-1 at shared targets unclear
    • Structural basis of THAP–HCF-1 interaction not determined
  10. 2011 High

    The discovery that OGT both O-GlcNAcylates HCF-1N and proteolytically cleaves HCF-1PRO repeats within its own active site fundamentally redefined HCF-1 maturation as an OGT-dependent process, linking nutrient sensing to HCF-1 function.

    Evidence In vitro cleavage assays, mutagenesis, mass spectrometry, siRNA, cell-cycle analysis

    PMID:21295698

    Open questions at the time
    • How proteolysis is temporally regulated in vivo unknown
    • Whether all six PRO repeats are cleaved equivalently not established
  11. 2013 High

    Multiple advances converged: the crystal structure of OGT bound to HCF-1PRO revealed the cleavage mechanism (pyroglutamate product); ChIP-seq in HeLa cells showed HCFC1 at ~5,400 CpG-island promoters with ZNF143/THAP11/GABP/YY1; and missense HCFC1 Kelch-domain mutations were identified as the cause of X-linked cblX disorder through transcriptional failure at the MMACHC promoter.

    Evidence Crystal structure with mutagenesis (OGT); ChIP-seq (HeLa); exome sequencing, ChIP, siRNA in patient fibroblasts (cblX)

    PMID:23539139 PMID:24011988 PMID:24311690

    Open questions at the time
    • Whether all ~5,400 bound promoters are functionally regulated by HCF-1 unknown
    • Structural basis for Kelch domain mutations causing cblX not resolved
    • Full spectrum of cblX-affected target genes beyond MMACHC not catalogued
  12. 2015 High

    The ACTACA DNA motif shared by THAP11 and ZNF143 was shown to direct HCFC1 recruitment to chromatin via CRISPR mutagenesis of endogenous promoters, establishing the cis-regulatory basis for the THAP11/ZNF143/HCFC1 module.

    Evidence CRISPR-Cas9 editing of endogenous promoters, ChIP, gene expression analysis

    PMID:26416877

    Open questions at the time
    • Whether other DNA motifs recruit HCFC1 independently of THAP11/ZNF143 not tested
    • Role of GABP and YY1 in HCFC1 recruitment not mechanistically distinguished
  13. 2016 High

    Separation-of-function OGT mutants demonstrated that HCF-1 proteolysis and O-GlcNAc glycosylation use overlapping but mechanistically separable catalytic routes within the same OGT active site, with a specific TPR contact required only for cleavage.

    Evidence Systematic mutagenesis of OGT catalytic and TPR domains with in vitro glycosylation and cleavage assays

    PMID:27056667

    Open questions at the time
    • In vivo consequences of selectively ablating OGT cleavage versus glycosylation not tested
    • Whether other OGT substrates compete with HCF-1 for cleavage unknown
  14. 2019 High

    HCF-1 was shown to couple glucose sensing to lipogenic gene expression: glucose-stimulated O-GlcNAcylation of HCF-1 enables its binding to ChREBP, followed by OGT recruitment and ChREBP activation, with H3K4me3 and PHF2 demethylase activity at lipogenic promoters.

    Evidence Co-IP, ChIP, O-GlcNAcylation assays, glucose stimulation, genetic knockdown

    PMID:31227231

    Open questions at the time
    • Whether HCF-1 O-GlcNAcylation is reversible and dynamically regulated unknown
    • Relative contribution of HCF-1 versus other ChREBP cofactors not established
  15. 2022 High

    Mouse models of Hcfc1/Ronin (Thap11) mutations revealed that the HCFC1–RONIN axis regulates not only MMACHC but also ribosome biogenesis genes, with mutant phenotypes consistent with ribosomopathy, broadening the disease mechanism beyond cobalamin metabolism.

    Evidence Mouse genetic models, transcriptome analysis, metabolic phenotyping

    PMID:35013307

    Open questions at the time
    • Which ribosome protein genes are direct versus indirect targets not fully resolved
    • Whether ribosomopathy phenotypes are independent of cobalamin deficiency not established
  16. 2025 Medium

    Hepatocyte-specific HCF-1 deletion revealed that HCF-1 post-translationally stabilizes OGT protein and sustains global O-GlcNAcylation, establishing a reciprocal regulatory relationship between HCF-1 and OGT beyond the known OGT→HCF-1 direction.

    Evidence Conditional knockout mouse model, immunofluorescence, western blot, RT-qPCR

    PMID:40754593

    Open questions at the time
    • Mechanism of HCF-1-dependent OGT stabilization not determined
    • Whether this relationship operates in non-hepatic tissues unknown
    • Single lab, not independently confirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include how HCF-1 selects between activating (MLL/Set1) and repressive (Sin3-HDAC) complexes at individual promoters, the structural basis of disease-causing Kelch domain mutations in cblX, the mechanism of HCF-1 Golgi sequestration in neurons, and whether the splicing function of HCF-1 is physiologically significant.
  • No structure of the full-length HCF-1 or Kelch domain with disease mutations
  • Splicing role described by a single lab and not replicated
  • In vivo significance of Golgi sequestration mechanism not established beyond neurons

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0060090 molecular adaptor activity 4 GO:0042393 histone binding 3
Localization
GO:0005634 nucleus 4 GO:0005694 chromosome 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 7 R-HSA-1640170 Cell Cycle 5 R-HSA-392499 Metabolism of proteins 4 R-HSA-4839726 Chromatin organization 4 R-HSA-1643685 Disease 2
Partners
ASXL1BAP1E2F1HSP90AA1OGTSIRT1THAP11ZNF143
Complex memberships
BAP1/ASXL1 (PR-DUB) complexSet1/MLL H3K4 methyltransferase complexSin3-HDAC complexVP16-induced complex (VIC)

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Separate regions of HCF-1 critical for cell proliferation associate with the Sin3 histone deacetylase (HDAC) complex and a human trithorax-related Set1/Ash2 histone H3-K4 methyltransferase (HMT) complex; HCF-1 tethers these two complexes together, and the transcriptional activator VP16 selectively binds HCF-1 associated with the Set1/Ash2 HMT complex in the absence of the Sin3 HDAC complex. Co-immunoprecipitation, mass spectrometry, in vitro binding assays, histone methyltransferase activity assays Genes & development High 12670868
2007 HCF-1 associates with both activator (E2F1, E2F3a) and repressor (E2F4) E2F proteins in a cell-cycle-selective manner; during the G1-to-S phase transition, HCF-1 recruits MLL and Set-1 histone H3K4 methyltransferases to E2F-responsive promoters, inducing histone methylation and transcriptional activation. Co-immunoprecipitation, chromatin immunoprecipitation (ChIP), reporter assays, cell-cycle synchronization Molecular cell High 17612494
2011 O-GlcNAc transferase (OGT) both O-GlcNAcylates the HCF-1N subunit and directly cleaves HCF-1 at the HCF-1PRO repeat sequences, mediating the proteolytic maturation of HCF-1 into HCF-1N and HCF-1C subunits; replacement of the HCF-1PRO repeats by a heterologous cleavage signal permits proteolysis but fails to activate HCF-1C M-phase functions. In vitro cleavage assays, mutagenesis of HCF-1PRO repeats, mass spectrometry, siRNA knockdown, cell-cycle phenotype analysis Cell High 21295698
2013 The tetratricopeptide-repeat (TPR) domain of OGT binds the C-terminal portion of an HCF-1 proteolytic repeat such that the cleavage region lies in the glycosyltransferase active site; cleavage occurs between cysteine and glutamate residues producing a pyroglutamate product; converting the cleavage-site glutamate to serine converts the proteolytic repeat into a glycosylation substrate. Crystal structure of OGT:HCF-1PRO complex, mutagenesis, in vitro cleavage and glycosylation assays Science High 24311690
2003 Proteolytic processing of HCF-1 is necessary to separate two distinct cell-cycle functions: the HCF-1N subunit promotes G1-phase progression, while the HCF-1C subunit is required for proper cytokinesis/exit from mitosis. siRNA knockdown of HCF-1 in multiple cell lines, expression of separate HCF-1N and HCF-1C subunits, cell-cycle phenotype analysis The EMBO journal High 12743030
2004 HCF-1C subunit depletion causes a switch from monomethyl to dimethyl lysine 20 of histone H4 (H4-K20) during mitosis and leads to defective chromosome alignment and segregation; HCF-1C regulates expression of the H4-K20 methyltransferase PR-Set7, and upregulation of PR-Set7 upon HCF-1 loss causes improper mitotic H4-K20 methylation and cytokinesis defects. siRNA knockdown, chromatin fractionation, quantitative ChIP, immunofluorescence, western blot Molecular cell High 15200950
2001 HCF-1 is naturally bound to chromatin in uninfected cells through its VP16-interaction domain; a proline-to-serine mutation in tsBN67 cells causes temperature-sensitive dissociation of HCF-1 from chromatin prior to cell proliferation arrest, establishing chromatin association as essential for HCF-1's role in cell proliferation. Chromatin fractionation, temperature-shift experiments, co-immunoprecipitation Molecular and cellular biology High 11340173
2009 BAP1 deubiquitinase interacts with HCF-1 via its HCF-1 binding motif and deubiquitinates Lys-48-linked polyubiquitin chains on the HCF-1N Kelch domain; this interaction is required for BAP1-mediated regulation of cell proliferation. Mass spectrometry of co-purified proteins, co-immunoprecipitation, ubiquitination assays, RNAi, dominant-negative mutant analysis The Journal of biological chemistry High 19815555
2008 C. elegans HCF-1 physically associates with DAF-16/FOXO and limits DAF-16 recruitment to target gene promoters; loss of hcf-1 results in daf-16-dependent lifespan extension of up to 40% and altered expression of DAF-16-regulated genes. Co-immunoprecipitation, ChIP, genetic epistasis (double mutants), lifespan assays PLoS biology High 18828672
2011 In C. elegans, HCF-1 acts downstream of SIR-2.1 to regulate DAF-16/FOXO target gene expression; SIR-2.1/SIRT1 and HCF-1 form protein complexes in both worms and mammalian cells; mammalian HCF-1 represses FOXO/SIRT1 target genes analogously. Genetic epistasis, gene expression profiling, co-immunoprecipitation in C. elegans and mammalian cells PLoS genetics High 21909281
2010 THAP1 associates with HCF-1 via a consensus HCF-1 binding motif (HBM) in vitro and in vivo, and endogenous THAP1 mediates recruitment of HCF-1 to the RRM1 promoter during endothelial cell proliferation; HCF-1 is essential for THAP1-dependent transcriptional activation of RRM1. Proteomic analysis, co-immunoprecipitation, in vitro binding, ChIP, RNAi The Journal of biological chemistry High 20200153
2013 HCFC1 binds to consensus sites in the MMACHC promoter and is required for transcriptional regulation of MMACHC; siRNA-mediated knockdown of HCFC1 results in coordinate downregulation of MMACHC mRNA, and missense mutations in the HCFC1 kelch domain in cblX patients cause severe reduction of MMACHC mRNA and protein. Exome sequencing, ChIP (consensus binding sites), siRNA knockdown, RT-PCR, western blot American journal of human genetics High 24011988
2013 In HeLa cells, HCFC1 is bound to ~5,400 active CpG-island promoters and co-localizes with ZNF143, THAP11 (Ronin), GABP, and YY1 transcription factors at ~90% of HCFC1-bound promoters, establishing HCFC1 as a broadly acting transcriptional scaffold. ChIP-seq, motif analysis, co-localization analysis Genome research High 23539139
2010 Ronin (THAP11) binds with HCF-1 to a highly conserved enhancer element and together regulate genes involved in transcription initiation, mRNA splicing, and cell metabolism to support ES cell self-renewal; Ronin/HCF-1 both represses and activates target genes. ChIP-seq, co-immunoprecipitation, gene expression profiling, loss-of-function Genes & development High 20581084
2000 HCF-1 contains two matched pairs of self-association sequences (SAS1 and SAS2); SAS1 consists of a 43-amino-acid HCF-1N region that associates with a tandem pair of fibronectin type 3 (Fn3) repeats in the HCF-1C subunit; HCF-1C contains a nuclear localization signal that recruits HCF-1N subunits to the nucleus. Co-immunoprecipitation, deletion mutagenesis, subcellular localization assays Molecular and cellular biology High 10958670
2012 The SAS1 self-association elements from HCF-1N and HCF-1C subunits form an interdigitated fibronectin type 3 (Fn3) tandem repeat structure; the C-terminal NLS recruited by this interdigitated SAS1 structure is required for effective formation of the HSV VP16-induced transcriptional regulatory complex. Crystal structure of SAS1, mutagenesis, VP16-induced complex formation assays Proceedings of the National Academy of Sciences of the United States of America High 23045687
2016 OGT-mediated glycosylation and HCF-1 proteolysis occur through separable mechanisms within the same active site; a specific TPR domain contact with HCF-1 is critical for proteolysis but not Ser/Thr glycosylation; key catalytic residues and UDP-GlcNAc oxygen required for glycosylation are dispensable for proteolysis. Mutagenesis of OGT catalytic and TPR domains, in vitro glycosylation and cleavage assays, engineered single-activity OGT enzymes Genes & development High 27056667
2015 The HCF-1PRO repeat contains distinct OGT-binding sites: the cleavage-site glutamate inhibits OGT/UDP-GlcNAc association, while a novel OGT-binding sequence near the first HCF-1PRO-repeat cleavage signal enhances cleavage. In vitro OGT binding and cleavage assays, mutagenesis, mass spectrometry PloS one High 26305326
2006 The HCF-1 processing/PRO domain interacts with the transcriptional coactivator/corepressor FHL2; this interaction is specific to the non-processed (uncleavaged) HCF-1 and costimulates transcription of an HCF-1-dependent target gene, establishing that site-specific proteolysis of HCF-1 regulates its interaction with protein cofactors. Co-immunoprecipitation, reporter assays, mutational analysis of PRO repeats Proceedings of the National Academy of Sciences of the United States of America Medium 16624878
2002 The C-terminal WYF domain of HCF-1 interacts with the MYND domain of PDCD2; overexpression of PDCD2 suppresses HCF-1 complementation of the tsBN67 temperature-sensitive proliferation defect, identifying PDCD2 as a negative regulator of HCF-1. Co-immunoprecipitation, complementation assay in tsBN67 cells, overexpression of dominant-interfering domains Oncogene Medium 12149646
2002 Inactivation of pRb family members (pRb, p107, p130) by SV40 large T antigen or adenovirus E1A rescues both the cell proliferation and cytokinesis defects of HCF-1-deficient tsBN67 cells without restoring HCF-1 chromatin association, placing HCF-1 upstream of or in opposition to pRb family function in cell cycle control. Genetic rescue (oncoprotein expression), temperature-shift experiments, chromatin fractionation Molecular and cellular biology Medium 12215534
2002 HCF-1 is required for spliceosome assembly and pre-mRNA splicing; it interacts with complexes containing U1 and U5 splicing snRNPs in uninfected cells; the tsBN67 missense mutation disrupts these interactions at non-permissive temperature and causes inefficient spliceosome assembly. Co-immunoprecipitation with snRNPs, in vitro splicing assays in nuclear extracts, rescue by wild-type HCF-1 expression The EMBO journal Medium 12456665
2010 HCF-1 localizes to HSV-1 DNA replication sites late in infection; HCF-1 interacts directly and simultaneously with both HSV DNA replication proteins and the cellular histone chaperone Asf1b; depletion of Asf1b results in significantly reduced viral DNA accumulation. Co-immunoprecipitation, immunofluorescence localization to viral replication foci, siRNA depletion with viral DNA quantification Proceedings of the National Academy of Sciences of the United States of America Medium 20133788
2009 E2F1 associates with HCF-1 through a short DHQY sequence; this interaction enables E2F1 to stimulate both DNA damage and apoptosis; HCF-1 and the MLL family of H3K4 methyltransferases have important functions in E2F1-induced apoptosis; sequence changes in the E2F1 HCF-1-binding site modulate E2F1-induced apoptosis up and down. Mutagenesis of E2F1 HCF-1-binding motif, co-immunoprecipitation, apoptosis and DNA damage assays, siRNA knockdown The EMBO journal Medium 19763085
2003 The HCF-binding motif (HBM) in Krox20 and E2F4 mediates association with the HCF-1 beta-propeller (Kelch) domain; Krox20 requires a functional HBM for both transactivation and HCF-1 association; the HCF-1C activation domain contributes to activation by Krox20, possibly through recruitment of p300. Co-immunoprecipitation, mutagenesis of HBM, reporter assays, pulldown The Journal of biological chemistry Medium 14532282
2002 HCF-1 contains an activation domain (HCF-1AD) in its C-terminal subunit required for maximal transactivation by VP16 and LZIP; co-expression of p300 augments HCF-1AD activity; cells lacking the HCF-1AD show reduced HSV immediate-early gene expression and lower viral titers. Reporter assays, mutagenesis, HSV infection with titer measurement Proceedings of the National Academy of Sciences of the United States of America Medium 12271126
2008 In sensory neurons, HCF-1 is specifically sequestered at the Golgi apparatus (not the ER); disruption of the Golgi causes rapid relocalization of HCF-1 to the nucleus, correlating with a regulatory mechanism for HSV reactivation. Immunofluorescence, organelle co-localization, Golgi disruption experiments in primary neuronal cultures Journal of virology Medium 18667495
2002 The nuclear export factor HPIP contains a functional HCF-binding motif that interacts with the HCF-1 beta-propeller domain; HPIP shuttles between nucleus and cytoplasm in a CRM1-dependent manner, and its overexpression leads to accumulation of HCF-1 in the cytoplasm. Co-immunoprecipitation, subcellular localization assays, CRM1 inhibitor treatment, overexpression The Journal of biological chemistry Medium 12235138
2007 Loss of C. elegans HCF-1 leads to reduced levels of phospho-histone H3 serine 10 (H3S10P) in viable embryos; mammalian cells with defective HCF-1 also display mitotic H3S10P defects, suggesting a conserved role for HCF-1 in regulating mitotic histone phosphorylation. Genetic deletion in C. elegans, immunofluorescence, temperature-shift experiments in mammalian cells PloS one Medium 18043729
2019 HCF-1 is O-GlcNAcylated in response to glucose as a prerequisite for its binding to ChREBP; HCF-1 then recruits OGT to O-GlcNAcylate ChREBP and promote its activation; the HCF-1:ChREBP complex at lipogenic gene promoters regulates H3K4 trimethylation and recruits the histone demethylase PHF2 for epigenetic activation. Co-immunoprecipitation, ChIP, O-GlcNAcylation assays, glucose-stimulation experiments, genetic knockdown Molecular cell High 31227231
2019 HSP90 maintains the stability of HCFC1 protein in the nucleus; HSP90 inhibition leads to loss of HCFC1 and reduced expression of HCFC1-targeted cell-cycle genes. Systematic nuclear HSP90 interactome analysis (three orthogonal methods), biochemical stability assays, gene expression analysis Cell reports Medium 31693902
2012 THAP11 associates physically with HCF-1 and recruits it to target promoters; THAP11-mediated gene regulation and chromatin association require HCF-1, while HCF-1 recruitment at THAP11 target genes requires THAP11, establishing mutual dependence. Co-immunoprecipitation, ChIP, siRNA knockdown, gene expression profiling Molecular and cellular biology Medium 22371484
2015 The ACTACA submotif shared by THAP11 and ZNF143 directs recruitment of THAP11 and HCFC1 to ZNF143-occupied loci; CRISPR-Cas9-mediated alteration of the ACTACA submotif at endogenous promoters alters gene transcription and histone modifications, establishing the DNA sequence basis for THAP11/ZNF143/HCFC1 complex chromatin recruitment. CRISPR-Cas9 mutagenesis, chromosomally integrated synthetic constructs, ChIP, gene expression analysis Molecular and cellular biology High 26416877
2020 HCF-1 activates CDC42 expression by binding to the -881 to -575 region upstream of the CDC42 transcription start site; overexpression of constitutively active CDC42F28L rescues G1-phase delay and multinucleate mitotic defects caused by HCF-1 loss. ChIP, promoter reporter assays, siRNA knockdown, rescue by CDC42 overexpression Cell death & disease Medium 33097698
2021 SETD5 regulates RNA polymerase II pausing and release at E2F target gene promoters in hematopoietic stem cells in cooperation with HCF-1 and the PAF1 complex; SETD5 and HCF-1 co-occupy E2F target promoters. ChIP-seq, co-immunoprecipitation, conditional knockout, transcriptome analysis Leukemia Medium 34853439
2022 HCFC1 and RONIN (THAP11) jointly regulate MMACHC expression and also regulate genes encoding ribosome protein subunits; mouse models of Hcfc1/Ronin mutations show reduced expression of ribosome biogenesis genes and phenotypes consistent with ribosomopathy in addition to cblC-like metabolic defects. Mouse genetic models, transcriptome analysis, metabolic phenotyping Nature communications High 35013307
2018 The conserved threonine-rich region of the HCF-1PRO repeat is tightly bound by the OGT TPR region and activates both OGT glycosylation and proteolysis activities; linkage of this region to heterologous sequences potentiates both Ser glycosylation and cleavage of non-HCF-1PRO sequences containing an appropriately positioned glutamate. In vitro glycosylation assays with co-substrate analogs, domain-swap mutagenesis, mass spectrometry The Journal of biological chemistry High 30224358
2024 KDM2A (lysine demethylase targeting H3K36me3) recruits HCF-1 and E2F1 to promoters of meiosis-entry genes (Stra8, Meiosin, Spo11, Sycp1) in male germ cells; KDM2A deficiency disrupts H3K36me2/3 deposition and impairs meiotic entry. Conditional knockout, ChIP, co-immunoprecipitation, spermatogenesis phenotype analysis The EMBO journal Medium 39160277
2024 In C. elegans, SET-26 recruits HCF-1 to chromatin (HCF-1 localization is largely dependent on functional SET-26), and together they antagonize the histone deacetylase HDA-1 to regulate longevity and gene expression; HDA-1 opposes SET-26 and HCF-1 at a subset of common target gene promoters. Genetic epistasis, ChIP, transcriptome analysis, lifespan assays Nature communications Medium 38485937
2025 Hepatocyte-specific deletion of HCF-1 causes progressive loss of OGT protein levels and global O-GlcNAcylation without altering OGT mRNA, indicating post-translational regulation of OGT by HCF-1; HCF-1 loss results in reduced nuclear OGT and O-GlcNAcylation, mimicking fasting conditions. Conditional knockout mouse model, immunofluorescence, western blot, RT-qPCR, histology Scientific reports Medium 40754593
2026 HCF-1 binds to the C-terminal ~200 amino acids of ASXL1 and promotes ASXL1 turnover in a proteasome-dependent manner; HCF-1 and BAP1 show reciprocal antagonism in association with ASXL1, and deletion of the HCF-1-binding region stabilizes ASXL1. P2A dual-reporter stability assay, co-immunoprecipitation, proteasome inhibition, domain deletion mutagenesis FASEB journal Medium 41968849
2016 HCF1 and OCT2 bind cooperatively with EBNA1 at the Epstein-Barr virus OriP; HCF1 depletion leads to loss of H3K4me3 and H3 acetylation at EBV latency promoters and gain of H3K9me3, and results in loss of EBV episomes and viral reactivation. ChIP, co-immunoprecipitation, siRNA knockdown, episome quantification Journal of virology Medium 27009953
2013 HCF-1 is required for INS-1 pancreatic β-cell glucose-stimulated insulin secretion; HCF-1 and E2F1 co-localize to the Pdx1 promoter by ChIP, and HCF-1 loss reduces Pdx1 expression. siRNA knockdown, glucose-stimulated insulin secretion assay, ChIP PloS one Medium 24250814
2024 HSP90 inhibition reduces TFEB transcription by decreasing HSP90AA1-HCFC1 interaction, which prevents HCFC1 from binding to the TFEB proximal promoter region, leading to reduced LC3 and increased mitochondria-derived vesicle formation. Co-immunoprecipitation, ChIP, western blot, siRNA knockdown Autophagy Medium 39461872

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2003 Human Sin3 deacetylase and trithorax-related Set1/Ash2 histone H3-K4 methyltransferase are tethered together selectively by the cell-proliferation factor HCF-1. Genes & development 337 12670868
2009 The deubiquitinating enzyme BAP1 regulates cell growth via interaction with HCF-1. The Journal of biological chemistry 223 19815555
2011 O-GlcNAc transferase catalyzes site-specific proteolysis of HCF-1. Cell 209 21295698
2007 E2F activation of S phase promoters via association with HCF-1 and the MLL family of histone H3K4 methyltransferases. Molecular cell 206 17612494
2001 Loss of HCF-1-chromatin association precedes temperature-induced growth arrest of tsBN67 cells. Molecular and cellular biology 168 11340173
2013 HCF-1 is cleaved in the active site of O-GlcNAc transferase. Science (New York, N.Y.) 160 24311690
2003 Proteolytic processing is necessary to separate and ensure proper cell growth and cytokinesis functions of HCF-1. The EMBO journal 113 12743030
2013 An X-linked cobalamin disorder caused by mutations in transcriptional coregulator HCFC1. American journal of human genetics 103 24011988
2010 Ronin/Hcf-1 binds to a hyperconserved enhancer element and regulates genes involved in the growth of embryonic stem cells. Genes & development 98 20581084
2008 Caenorhabditis elegans HCF-1 functions in longevity maintenance as a DAF-16 regulator. PLoS biology 94 18828672
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2009 E2F1 mediates DNA damage and apoptosis through HCF-1 and the MLL family of histone methyltransferases. The EMBO journal 55 19763085
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2016 HCF1 and OCT2 Cooperate with EBNA1 To Enhance OriP-Dependent Transcription and Episome Maintenance of Latent Epstein-Barr Virus. Journal of virology 15 27009953
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2021 SETD5 modulates homeostasis of hematopoietic stem cells by mediating RNA Polymerase II pausing in cooperation with HCF-1. Leukemia 12 34853439
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2021 A reinterpretation of critical flicker-frequency (CFF) data reveals key details about light adaptation and normal and abnormal visual processing. Progress in retinal and eye research 10 34506951
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2023 Deletion of the Transcriptional Coactivator HCF-1 In Vivo Impairs the Removal of Repressive Heterochromatin from Latent HSV Genomes and Suppresses the Initiation of Viral Reactivation. mBio 8 36692302
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