Affinage

CXXC1

CXXC-type zinc finger protein 1 · UniProt Q9P0U4

Round 2 corrected
Length
656 aa
Mass
75.7 kDa
Annotated
2026-04-28
83 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CXXC1 (CFP1/CGBP) is a CXXC zinc-finger protein that selectively binds unmethylated CpG dinucleotides and functions as a dedicated subunit of the mammalian Set1A and Set1B COMPASS complexes, directing H3K4 trimethylation to CpG-island-associated promoters and active transcription start sites (PMID:10688657, PMID:16253997, PMID:17355966). By tethering COMPASS to euchromatin, CXXC1 restricts H3K4me3 deposition away from heterochromatin, maintains appropriate DNMT1 levels and global cytosine methylation, and orchestrates additional histone modifications including H3K27me3 and H3K36me3 (PMID:19951360, PMID:15923607, PMID:33621320). CXXC1 is essential for embryonic viability, hematopoietic differentiation, T-cell development and regulatory T-cell function—where it physically interacts with FOXP3 to co-occupy target loci—as well as oocyte epigenetic maturation, meiotic crossover formation, and zygotic genome activation (PMID:11604496, PMID:25470594, PMID:27210293, PMID:40183773, PMID:28768200, PMID:32094118, PMID:41419741). CDK1-mediated phosphorylation and degradation of CXXC1 during meiotic resumption couples the H3K4me3 epigenetic program to cell-cycle progression in oocytes (PMID:30154440).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2000 High

    The initial molecular identity of CXXC1 was established as a ubiquitous transcriptional activator that recognizes unmethylated CpG dinucleotides through its CXXC domain, defining its DNA-binding specificity.

    Evidence Ligand screening, EMSA, and reporter assays in human cells

    PMID:10688657

    Open questions at the time
    • No interacting chromatin-modifying complexes identified
    • Trans-activation mechanism unknown
  2. 2001 High

    Knockout revealed that CXXC1 is essential for post-implantation mammalian development, establishing its requirement in vivo beyond cell-autonomous transcription.

    Evidence Homozygous Cxxc1 knockout mice with peri-implantation lethality; blastocyst outgrowth assay

    PMID:11604496

    Open questions at the time
    • Molecular pathways responsible for lethality unknown
    • Whether CXXC1 acts via chromatin modification not yet determined
  3. 2002 High

    Subnuclear localization studies placed CXXC1 in euchromatic speckles co-localizing with acetylated histones and human trithorax, hinting at membership in a histone-modifying complex.

    Evidence Confocal immunofluorescence, nuclear matrix fractionation, and deletion mutant mapping

    PMID:12200428

    Open questions at the time
    • Direct complex membership not yet biochemically confirmed
    • Functional consequence of euchromatic targeting unresolved
  4. 2005 High

    Biochemical purification definitively identified CXXC1 as a subunit of the mammalian Set1/COMPASS H3K4 methyltransferase complex and showed that CXXC1-null ES cells paradoxically have elevated H3K4me but reduced H3K9me and cytosine methylation with impaired differentiation, linking CXXC1 to both H3K4 methylation control and DNA methylation maintenance through DNMT1 stabilization.

    Evidence Co-IP/mass spectrometry of Set1/COMPASS, in vitro HMT assay, Cxxc1-null ES cells with methylation-sensitive Southern blotting and DNMT activity assays, rescue experiments

    PMID:15923607 PMID:16253997

    Open questions at the time
    • How CXXC1 restrains rather than promotes H3K4me not mechanistically resolved
    • DNMT1 stabilization mechanism uncharacterized
  5. 2007 High

    CXXC1 was shown to be shared between Set1A and Set1B complexes, and the Wdr82 subunit of Set1A/CFP1 complex was found to recruit the complex to Ser5-phosphorylated RNA Pol II at transcription start sites, explaining TSS-specific H3K4me3 deposition.

    Evidence Co-IP, mass spectrometry, domain mapping, GST pulldown with phospho-CTD peptides, ChIP and siRNA in human cells

    PMID:17355966 PMID:17998332

    Open questions at the time
    • Whether CXXC1 DNA-binding or Wdr82-RNAPII interaction is the dominant targeting mechanism unresolved
    • Set1B-specific recruitment mechanism not addressed
  6. 2009 High

    Structure-function analysis resolved that full-length CXXC1 is required to restrict Setd1A and H3K4me3 to euchromatin; either the DNA-binding or Set1-interacting half alone stabilizes Setd1A protein levels but cannot prevent heterochromatic mislocalization.

    Evidence CFP1-null ES cells reconstituted with truncation/point mutants, immunofluorescence and Western blot

    PMID:19951360

    Open questions at the time
    • Structural basis for the bridging function not determined
    • Whether heterochromatic H3K4me3 is functionally deleterious not tested
  7. 2014 High

    Genome-wide ChIP-seq distinguished CXXC1/Set1C from Mll2 at active versus bivalent promoters, and conditional knockout demonstrated that CXXC1 is essential for hematopoietic progenitor differentiation but dispensable for the most primitive stem cells.

    Evidence ChIP-seq in multiple KO mES cells; Mx1-Cre inducible Cxxc1 KO with bone marrow transplantation and flow cytometry

    PMID:24423662 PMID:25470594

    Open questions at the time
    • Direct target genes mediating differentiation block in hematopoiesis not identified
    • Whether CXXC1 loss alters Set1C versus Mll1 redistribution genome-wide not tested
  8. 2016 High

    Two independent studies demonstrated that CXXC1 physically interacts with the meiotic recombination determinant PRDM9 and that CXXC1 controls T-cell development by maintaining H3K4me3 at key thymocyte survival and signaling gene promoters.

    Evidence Y2H, co-IP from spermatocytes, and in vitro binding for PRDM9; T-cell-specific Cxxc1 KO with ChIP-seq and RORγt rescue for thymocyte phenotype

    PMID:27210293 PMID:27932493

    Open questions at the time
    • Functional requirement of CXXC1-PRDM9 interaction for meiotic recombination not genetically tested in mammals
    • Whether CXXC1 acts purely via Set1C or has Set1-independent roles in T cells unknown
  9. 2017 High

    Oocyte-specific Cxxc1 deletion revealed that CFP1-mediated H3K4me3 is essential for oocyte transcription, meiotic maturation, and maternal-zygotic transition, establishing CXXC1 as a central epigenetic regulator of female germ cell development.

    Evidence Oocyte-specific Cxxc1 KO with ChIP-seq, RNA-seq, immunofluorescence, and IVF

    PMID:28768200

    Open questions at the time
    • Specific transcriptional targets mediating meiotic arrest not fully delineated
    • Whether CFP1 acts solely through Set1C in oocytes not resolved
  10. 2018 High

    CDK1-triggered degradation and phosphorylation of CFP1 was identified as a cell-cycle coupling mechanism in oocytes, and conditional KO in male germ cells showed that, contrary to the yeast Spp1 paradigm, mammalian CXXC1 is dispensable for PRDM9-directed meiotic DSB formation in spermatocytes.

    Evidence Oocyte CFP1 degradation mutant analysis with pharmacological CDK1 inhibition; two independent male germ-cell Cxxc1 KO models with DMC1-SSDS, ChIP, and fertility testing

    PMID:30154440 PMID:30365547

    Open questions at the time
    • How CDK1-mediated CFP1 degradation is molecularly executed (E3 ligase identity) unknown
    • Apparent contradiction between dispensability in spermatocytes and requirement in later meiotic stages not fully resolved
  11. 2019 High

    CXXC1 was shown to regulate adaptive immune polarization and paracrine signaling: it promotes Th17 differentiation by maintaining H3K4me3 at the Il6rα locus, and in oocytes it controls paracrine factor expression required for granulosa cell communication and ovulation.

    Evidence T-cell Cxxc1 KO with ChIP-seq, IL-6Rα rescue, EAE/infection models; oocyte Cxxc1 KO with RNA-seq and hormone stimulation

    PMID:31633019 PMID:31676962

    Open questions at the time
    • Full set of paracrine factors controlled by CXXC1 in oocytes not characterized
    • Whether CXXC1 regulation of IL-6Rα is conserved in human Th17 cells untested
  12. 2020 High

    A later conditional KO study showed that CXXC1-mediated H3K4me3 is essential for meiotic crossover formation in both sexes, with decreased H3K4me3 at DMC1-binding sites and improper crossover placement causing complete sterility—partially reconciling the apparent dispensability seen in earlier spermatocyte DSB studies.

    Evidence Stra8-Cre Cxxc1 KO with H3K4me3 ChIP-seq, MLH1/DMC1 immunofluorescence, and histological analysis in both sexes

    PMID:32094118

    Open questions at the time
    • Whether CXXC1 contributes to crossover designation versus DSB repair efficiency not separated
    • Different phenotypic severity across Cre-driver models not fully explained
  13. 2021 High

    Epigenomic profiling in CXXC1-null oocytes revealed that CXXC1 and MLL2 have non-overlapping H3K4me3 targets and that CXXC1 loss disrupts multiple histone marks (H3K27me3, H2AK119ub1, H3K36me3) and DNA methylation, demonstrating CXXC1's role in organizing a broader epigenetic landscape beyond H3K4me3 alone.

    Evidence CUT&TAG for multiple histone marks, WGBS for DNA methylation, RNA-seq in Cxxc1 KO oocytes

    PMID:33621320

    Open questions at the time
    • Whether cross-talk among marks is direct or through transcriptional changes not resolved
    • MLL2-independent vs. Set1C-specific CXXC1 functions not genetically separated
  14. 2022 High

    CXXC1-maintained H3K4me3 was linked to cytoplasmic mRNA decay competence and translational control in oocytes, establishing that CXXC1 coordinates nuclear epigenetic and cytoplasmic post-transcriptional programs and acts as a molecular timer for oocyte quality decline.

    Evidence Oocyte Cxxc1 KO with mRNA degradome sequencing, polysome profiling, and H3K4me3 CUT&TAG

    PMID:35680896

    Open questions at the time
    • Direct mechanistic link between H3K4me3 loss and mRNA decay pathway not elucidated
    • Whether this coupling exists outside oocytes untested
  15. 2025 High

    Multiple studies extended CXXC1's roles to regulatory T-cell function (via direct FOXP3 interaction), innate lymphoid cell homeostasis (via Klf4), zygotic genome activation in Xenopus, and DNA methylation remodeling during spermatogenesis, reinforcing CXXC1 as a versatile epigenetic hub across tissues and species.

    Evidence Treg-specific Cxxc1 KO with FOXP3 co-IP and ChIP-seq; ILC3-specific KO with Klf4 rescue; Xenopus Cxxc1 depletion with CUT&RUN and RNA-seq; spermatocyte RRBS integrated with ChIP-seq

    PMID:37429951 PMID:40045604 PMID:40183773 PMID:41419741

    Open questions at the time
    • Structural basis for CXXC1-FOXP3 interaction unknown
    • Whether CXXC1's ZGA role in Xenopus is conserved in mammals not tested
    • Relative contribution of Set1A vs. Set1B in each tissue context largely unaddressed

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of CXXC1's bifunctional bridging between unmethylated DNA and Set1 catalytic subunits; the identity of the E3 ligase mediating CDK1-triggered CXXC1 degradation; whether CXXC1 has Set1-independent functions in any context; and the mechanisms coupling CXXC1-dependent H3K4me3 to cytoplasmic mRNA dynamics.
  • No high-resolution structure of CXXC1 in complex with COMPASS
  • CDK1-dependent degradation pathway not molecularly defined
  • Set1-independent functions remain hypothetical

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0042393 histone binding 2
Localization
GO:0005634 nucleus 3 GO:0005654 nucleoplasm 3 GO:0005694 chromosome 2
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-4839726 Chromatin organization 5 R-HSA-1474165 Reproduction 4 R-HSA-168256 Immune System 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-1640170 Cell Cycle 2
Partners
ASH2LFOXP3PRDM9RBBP5SETD1ASETD1BWDR5WDR82
Complex memberships
Set1A/COMPASS (Set1C)Set1B/COMPASS

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 CXXC1 (hCGBP) was identified as a transcriptional activator that binds specifically to unmethylated CpG dinucleotides via its CXXC domain. The protein fails to bind methylated CpG, single-stranded DNA, or RNA, and trans-activates promoters containing CpG motifs but not those lacking them. Native hCGBP was detected as an 88-kDa protein by Western analysis and is ubiquitously expressed. Ligand screening, EMSA, Western blot, transcriptional activation reporter assays Molecular and cellular biology High 10688657
2001 Homozygous deletion of CGBP (Cxxc1) in mice results in embryonic lethality; mutant embryos die peri-implantation (absent by E6.5–12.5 dpc). CGBP-null blastocysts are viable and can form ICM and trophectoderm in vitro, indicating CGBP is essential for post-implantation development rather than blastocyst formation. Homologous recombination knockout, histological analysis, in vitro blastocyst outgrowth assay Molecular and cellular biology High 11604496
2002 CGBP (CFP1) localizes to nuclear speckles associated with euchromatin (DAPI-light regions), co-localizes with acetylated histones and some SC-35 splicing factor speckles, and associates with the nuclear matrix. Punctate subnuclear distribution requires signals within the acidic, basic, and coiled-coil domains, not the DNA-binding domain alone. CGBP co-localizes with human trithorax, suggesting co-membership in a multimeric histone-methylating complex. Confocal immunofluorescence, nuclear matrix fractionation, deletion mutant analysis, transcriptional activation assays The Journal of biological chemistry High 12200428
2005 CFP1 (CGBP/CXXC1) is a component of the mammalian Set1/COMPASS histone H3-Lys4 methyltransferase complex (analogous to yeast Set1/COMPASS). Co-immunoprecipitation and mass spectrometry identified CFP1 associated with a ~450 kDa complex containing mammalian homologues of six Set1/COMPASS subunits. In vitro, this human Set1/CFP1 complex produces mono-, di-, and trimethylated H3K4. ES cells lacking CFP1 show elevated H3K4 methylation and reduced H3K9 methylation, and CFP1 restricts Set1 methyltransferase activity during differentiation. Co-immunoprecipitation, mass spectrometry, in vitro histone methyltransferase assay, confocal microscopy, Western blot in Cxxc1-null ES cells The Journal of biological chemistry High 16253997
2005 CGBP-null embryonic stem cells show 60–80% reduction in global cytosine methylation (including hypomethylation of repetitive elements, single-copy genes, and imprinted genes), 30–60% reduction in total DNA methyltransferase activity, and decreased DNMT1 protein. CGBP-null ES cells are unable to differentiate (persistent Oct4 and alkaline phosphatase expression) and show increased apoptosis. All phenotypes are rescued by re-introduction of a CGBP expression vector. CGBP-null ES cell lines, methylation-sensitive Southern blotting, in vitro DNMT activity assay, Western blot, rescue with expression vector Molecular and cellular biology High 15923607
2007 CFP1 is a component of both the Set1A and Set1B histone H3-Lys4 methyltransferase complexes (~450 kDa each). A 123-amino acid fragment upstream of the Set1A SET domain is required for interaction with CFP1, Ash2, Rbbp5, and Wdr5. Set1A and Set1B localize to largely non-overlapping sets of euchromatic nuclear speckles. Co-immunoprecipitation, mass spectrometry, confocal microscopy, deletion analysis The Journal of biological chemistry High 17355966
2007 The Wdr82 component of the Setd1A/CFP1 complex binds the Ser5-phosphorylated C-terminal domain of RNA Pol II, recruiting the complex to transcription start sites. Depletion of Wdr82 reduces Setd1A occupancy and H3K4me3 at TSS without affecting RNAP II occupancy or target gene expression. This defines a mechanism for TSS-specific H3K4me3 deposition mediated through CFP1-containing Set1C. Co-immunoprecipitation, ChIP, siRNA knockdown, GST pulldown with phospho-CTD peptides Molecular and cellular biology High 17998332
2009 CFP1 (Cxxc1) restricts the Setd1A H3K4 methyltransferase complex to euchromatin. ES cells lacking CFP1 show decreased Setd1A levels and mislocalization of both Setd1A and H3K4me3 into heterochromatin. Structure-function analysis reveals that either the N-terminal (aa 1–367, DNA-binding) or C-terminal (aa 361–656, Setd1-interaction) fragment of CFP1 alone can restore normal Setd1A levels, but full-length CFP1 is required to restrict Setd1A and H3K4me3 to euchromatin. CXXC1-null ES cells, Western blot, immunofluorescence, structure-function analysis with CFP1 point mutants and fragments The FEBS journal High 19951360
2013 The CGBP (CFP1) CXXC domain binds unmethylated CpG DNA but with different affinity from MLL and DNMT1 CXXC domains. In the context of MLL-AF9 leukemia fusions, the CGBP CXXC domain cannot substitute for the MLL CXXC domain to support in vitro colony formation or in vivo leukemogenesis, despite allowing targeting to the Hoxa9 locus. This demonstrates functional specificity among CXXC domains that is linked to CpG protection from methylation. In vitro DNA binding affinity assays, colony forming assays, in vivo leukemogenesis, ChIP The Journal of biological chemistry Medium 23990460
2014 The Set1C subunit Cxxc1 (CFP1) is primarily bound to active (non-bivalent) promoters in mouse ES cells, in contrast to Mll2 which occupies bivalent promoters. This indicates that active promoters have more than one bound H3K4 methyltransferase, including Set1C, while bivalent promoters rely specifically on Mll2 for H3K4me3. ChIP-seq in Mll2 and Mll1 conditional KO mouse ES cells Development Medium 24423662
2014 Cfp1 (Cxxc1) is essential for hematopoiesis. Inducible deletion of Cxxc1 in adult mice causes near-complete loss of lineage-committed progenitors and mature hematopoietic cells, elevated apoptosis, and death within two weeks. The Lin-Sca-1+c-Kit+ (LSK) hematopoietic stem/progenitor population persists and expands in the absence of Cfp1, demonstrating that Cfp1 is required for the differentiation of hematopoietic progenitors but not for maintenance of the most primitive stem cell pool. Mx1-Cre inducible conditional KO, bone marrow transplantation, flow cytometry, histology PloS one High 25470594
2016 PRDM9 directly interacts with CXXC1 (a COMPASS complex member) through its KRAB domain, as shown by yeast two-hybrid, in vitro binding, and co-immunoprecipitation from mouse spermatocytes. CXXC1 also associates with the meiotic cohesin REC8 and the synaptonemal complex proteins SYCP3 and SYCP1, and PRDM9-bound complexes associate with these axis components. This suggests a model in which PRDM9-activated hotspot DNA is brought to the chromosomal axis via CXXC1. Yeast two-hybrid, in vitro binding assay, co-immunoprecipitation from spermatocytes Molecular biology of the cell Medium 27932493
2016 T-cell development in the thymus is severely impaired in Cxxc1-deficient mice. Genome-wide ChIP-seq shows that Cxxc1 directly controls expression of key thymocyte survival genes (RORγt) and T-cell receptor signaling genes (Zap70, CD8) by maintaining appropriate H3K4me3 at their promoters. Overexpression of RORγt partially rescues survival defects of Cxxc1-deficient thymocytes. T-cell-specific Cxxc1 conditional KO, ChIP-seq, flow cytometry, RORγt overexpression rescue Nature communications High 27210293
2017 CFP1 (encoded by Cxxc1) is required in oocytes for H3K4me3 accumulation and histone variant deposition onto chromatin during oocyte maturation. Deletion of CFP1 in developing oocytes causes global downregulation of transcription, failure to complete meiotic maturation, defects in cytoplasmic lattice formation and meiotic division, and inability to undergo maternal-zygotic transition after fertilization. Oocyte-specific Cxxc1 conditional KO, ChIP-seq, RNA-seq, immunofluorescence, in vitro fertilization Cell reports High 28768200
2017 The KRAB domain of PRDM9 is required for meiosis; its truncation leads to loss of PRDM9 function and altered meiotic prophase. CXXC1, a COMPASS complex member orthologous to yeast Spp1, was identified as a PRDM9 KRAB-domain interactor by yeast two-hybrid screens. CXXC1 also interacts with IHO1, an essential component of the meiotic DSB machinery. Yeast two-hybrid screen, meiotic phenotype analysis in truncation mutant mice Chromosoma Medium 28527011
2018 CFP1 (Cxxc1) coordinates H3K4me3 and meiotic cell cycle progression in mouse oocytes. Oocyte-specific Cxxc1 knockout, inhibition of CFP1 function, or abrogation of H3K4 methylation each causes delayed meiotic resumption and metaphase I arrest due to defective spindle assembly and chromosome misalignment—partially attributed to insufficient phosphorylation of H3 at threonine-3. CDK1 triggers cell division-coupled degradation and inhibitory phosphorylation of CFP1; preventing CFP1 degradation impairs meiotic maturation by causing CFP1 accumulation on chromosomes. Oocyte-specific Cxxc1 KO, pharmacological inhibition, immunofluorescence, phospho-specific antibodies, CFP1 degradation mutant analysis Nature communications High 30154440
2018 CFP1 occupies not only CGI-associated active TSS but also a substantial fraction of active non-CGI TSSs and enhancers of transcribed genes in human hematopoietic cells, and is mutually exclusive with H3K27me3. Relative to other TrxG subunits, CFP1 is specialized to TSSs. CpG-containing motifs are enriched in CFP1 peaks at CGI promoters. ChIP-seq in human hematopoietic cells Epigenetics & chromatin Medium 30292235
2018 CXXC1 is not essential for PRDM9-directed meiotic DSB formation in mouse spermatocytes. Conditional knockout of Cxxc1 in germ cells or specifically before meiosis onset results in fertile male mice with no effect on PRDM9 hotspot H3K4me3, DSB formation, or DSB repair—demonstrating that, unlike its yeast ortholog Spp1, mammalian CXXC1 is dispensable for linking PRDM9-activated hotspots to the DSB machinery. Two conditional Cxxc1 KO mouse models (Vasa-Cre and Stra8-Cre), DMC1-SSDS for DSB mapping, ChIP for H3K4me3, fertility analysis PLoS genetics High 30365547
2019 Cxxc1 promotes TH17 differentiation and prevents Treg differentiation by maintaining H3K4me3 at the Il6rα (IL-6Rα) gene promoter. T-cell-specific Cxxc1 deletion decreases IL-6Rα expression and impairs IL-6/STAT3 signaling, whereas IL-6Rα overexpression partially reverses TH17 defects. Genome-wide occupancy (ChIP-seq) confirms Cxxc1 binding at the Il6rα locus. T-cell-specific Cxxc1 KO, ChIP-seq, IL-6Rα overexpression rescue, EAE mouse model, Citrobacter infection model Science advances High 31633019
2019 CFP1-dependent H3K4me3 in oocytes is required cell-nonautonomously for ovarian follicle recruitment and ovulation. Oocyte-specific Cxxc1 knockout disrupts expression of key paracrine factors, impairs communication between oocyte and surrounding granulosa cells, and compromises FSH and LH signaling in granulosa cells, thereby reducing follicle growth and ovulation. Oocyte-specific Cxxc1 KO, RNA-seq in granulosa cells and oocytes, hormone stimulation, ovulation counting Cellular and molecular life sciences High 31676962
2020 CXXC1-mediated H3K4me3 is essential for proper meiotic crossover formation in mice. Conditional knockout of Cxxc1 in germ cells leads to complete sterility, decreased H3K4me3 from pachytene to MII, transcriptional disorder, delayed DSB repair, improper crossover formation, and precocious homologous chromosome segregation in pachytene/diplotene cells in both sexes. H3K4me3 enrichment at DMC1-binding sites is significantly decreased, implicating CXXC1-mediated H3K4me3 in DSB generation. Stra8-Cre conditional KO, ChIP-seq (H3K4me3), immunofluorescence (DMC1, MLH1, CO markers), spermatogenesis histology, oogenesis analysis Development High 32094118
2021 The Cxxc1 subunit of the Trithorax complex directs transcription of genes initially downregulated by TCR stimulation but upregulated again in a later phase of CD4+ T cell differentiation (Th1/Th2). Cxxc1 deficiency decreases expression of Trib3 (in Th1) and Klf2 (in Th2), and loss of Cxxc1 enhances pathogenicity in allergic airway inflammation. T-cell-specific Cxxc1 KO, RNA-seq, ChIP-seq, in vivo asthma model The Journal of experimental medicine Medium 33433611
2021 Oocyte-specific knockout of Cxxc1 globally decreases H3K4me3 (at promoters and gene bodies) and reveals that CXXC1 and MLL2 have nonoverlapping roles in mediating H3K4 trimethylation during oogenesis. Cxxc1 deletion also causes decrease in DNA methylation levels and affects H3K27me3, H2AK119ub1, and H3K36me3 distributions, particularly at high-DNA-methylation regions, demonstrating CXXC1's role in orchestrating multiple epigenetic modifications. Oocyte-specific Cxxc1 KO, CUT&TAG (H3K4me3, H3K27me3, H2AK119ub1, H3K36me3), WGBS (DNA methylation), RNA-seq Nucleic acids research High 33621320
2022 Oocyte-specific Cxxc1 knockout causes ooplasm changes associated with accelerated aging, including impaired maternal mRNA translation and degradation. CXXC1-maintained H3K4me3 is linked to mRNA decay competence, establishing that CXXC1 coordinates epigenetic and cytoplasmic maturation programs and acts as a timer for oocyte deterioration. Oocyte-specific Cxxc1 KO, mRNA degradome sequencing, polysome profiling, H3K4me3 CUT&TAG Nature communications High 35680896
2023 Cxxc1 is required for homeostasis and function of intestinal CCR6+ ILC3s. Disruption of Cxxc1 in ILC3s leads to aging-related phenotypes including dysregulated H3K4me3 at effector genes and susceptibility to bacterial and fungal infections. Klf4 is identified as a direct Cxxc1 target; Klf4 overexpression partially restores differentiation and functional defects in Cxxc1-deficient ILC3s. ILC3-specific Cxxc1 KO, ChIP-seq/H3K4me3 profiling, Klf4 overexpression, infection susceptibility assays Nature aging Medium 37429951
2025 CXXC1 interacts directly with the transcription factor FOXP3 in regulatory T cells and modulates H3K4me3 deposition at FOXP3 target gene loci. Cxxc1 deletion in Treg cells causes severe inflammatory disease, spontaneous T cell activation, and impaired immunosuppressive function. CXXC1 promotes expression of key Treg functional markers (e.g., CD25, CTLA-4, ICOS) under steady-state conditions; genome-wide CXXC1 binding overlaps with FOXP3-binding sites. Treg-specific Cxxc1 KO, co-immunoprecipitation (CXXC1-FOXP3 interaction), ChIP-seq, flow cytometry, inflammatory disease model eLife High 40183773
2025 In Xenopus laevis embryos, Cxxc1 (along with Kmt2b) ensures transcription-independent propagation of H3K4me3 from gametes to pre-ZGA embryos. Depletion of Cxxc1 reduces H3K4me3 and impairs accurate zygotic genome activation and expression of key ZGA pioneer transcription factors (Pou5f3.2, Sox3), demonstrating that H3K4 methylation pre-marking by Cxxc1 is required for proper embryonic development. Xenopus laevis Cxxc1 depletion (morpholino/CRISPR), CUT&RUN (H3K4me3 in gametes and embryos), RNA-seq, immunofluorescence Nature communications High 41419741
2025 CRISPR knockout screening of 1772 human TFs in epidermal progenitors identified CXXC1 as essential for epidermal homeostasis and differentiation. Genome-scale CRISPR knockout screen, massively parallel reporter assay Nature communications Low 40998781
2025 Analysis of DNA methylation changes in Cfp1 (Cxxc1) knockout spermatocytes by reduced-representation bisulfite sequencing reveals significant alterations in promoter methylation, particularly at genes associated with meiosis, transcription regulation, and chromatin remodeling. 21 direct CFP1 target genes were identified with reduced promoter methylation and CFP1 binding. Cxxc1 conditional KO spermatocytes, reduced-representation bisulfite sequencing, integration with ChIP-seq and microarray data Animal bioscience Medium 40045604
2026 Genetic depletion of CXXC1, a complex-specific subunit of Set1C/COMPASS, in melanoma cells suppresses global H3K4me3 and proliferation, and represses MYC- and E2F-driven transcriptional programs. This identifies Set1C/COMPASS as a melanoma-enriched epigenetic dependency mediated through CXXC1. Genetic dependency analysis (DepMap), CXXC1 siRNA/CRISPR depletion in melanoma cell lines, H3K4me3 ChIP, RNA-seq, single-cell analysis bioRxivpreprint Medium 41726895

Source papers

Stage 0 corpus · 83 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2014 A proteome-scale map of the human interactome network. Cell 977 25416956
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2012 Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 708 22939624
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2006 A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell 610 16713569
2010 An atlas of combinatorial transcriptional regulation in mouse and man. Cell 573 20211142
2005 High-throughput mapping of a dynamic signaling network in mammalian cells. Science (New York, N.Y.) 553 15761153
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2009 RAD6-Mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells. Cell 426 19410543
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2000 Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing. EMBO reports 281 11256614
2016 The cell proliferation antigen Ki-67 organises heterochromatin. eLife 265 26949251
2005 CpG-binding protein (CXXC finger protein 1) is a component of the mammalian Set1 histone H3-Lys4 methyltransferase complex, the analogue of the yeast Set1/COMPASS complex. The Journal of biological chemistry 258 16253997
2008 Molecular regulation of H3K4 trimethylation by Wdr82, a component of human Set1/COMPASS. Molecular and cellular biology 257 18838538
2014 Mll2 is required for H3K4 trimethylation on bivalent promoters in embryonic stem cells, whereas Mll1 is redundant. Development (Cambridge, England) 217 24423662
2016 A High-Density Map for Navigating the Human Polycomb Complexome. Cell reports 216 27705803
2007 Identification and characterization of the human Set1B histone H3-Lys4 methyltransferase complex. The Journal of biological chemistry 208 17355966
2012 Functional genomics identifies therapeutic targets for MYC-driven cancer. Proceedings of the National Academy of Sciences of the United States of America 203 22623531
2016 Structural basis for activity regulation of MLL family methyltransferases. Nature 187 26886794
2013 Quantitative dissection and stoichiometry determination of the human SET1/MLL histone methyltransferase complexes. Molecular and cellular biology 180 23508102
2011 Protein interactome reveals converging molecular pathways among autism disorders. Science translational medicine 180 21653829
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