Affinage

CXXC1

CXXC-type zinc finger protein 1 · UniProt Q9P0U4

Length
656 aa
Mass
75.7 kDa
Annotated
2026-06-09
53 papers in source corpus 26 papers cited in narrative 26 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CXXC1 (CFP1/CGBP) is the CpG-sensing, DNA-targeting subunit that couples recognition of unmethylated CpG dinucleotides to deposition of histone H3K4 trimethylation by the SETD1/Set1C (COMPASS) complex at active chromatin (PMID:10688657, PMID:19951360, PMID:30292235). Its CXXC domain binds DNA containing even a single unmethylated CpG, fails to bind when the CpG is mutated or methylated, and does not bind single-stranded DNA or RNA, providing the molecular basis for its specificity (PMID:10688657); a single CpG introduced into unrelated DNA is sufficient to create a binding site (PMID:10688657). CXXC1 localizes to active euchromatin and the nuclear matrix and is excluded from heterochromatin and metaphase chromosomes (PMID:12200428). As a component of the SETD1A H3K4 methyltransferase complex, CXXC1 stabilizes SETD1A protein and, through combined DNA-binding and complex-interaction activities, restricts SETD1A and H3K4me3 to euchromatin, preventing their heterochromatic mislocalization (PMID:19951360). It occupies active CpG-island and non-CpG-island transcription start sites and enhancers, with occupancy mutually exclusive of the Polycomb mark H3K27me3 (PMID:30292235), and operates on active rather than bivalent promoters, complementing MLL2 (PMID:24423662). CXXC1 is additionally required to maintain global cytosine methylation, acting through DNMT1 protein stability, since its loss reduces DNMT1 levels and global methylation by 60-80% without affecting de novo methyltransferase activity (PMID:15923607). Through these activities CXXC1 is essential for peri-implantation embryogenesis (PMID:11604496), hematopoietic stem/progenitor differentiation (PMID:25470594), oocyte maturation and meiotic competence (PMID:28768200, PMID:30154440, PMID:33621320), spermatogenesis and crossover formation (PMID:32094118), and multiple T-cell programs—directing thymocyte survival via RORγt (PMID:27210293), TH17/Treg balance via the Il6rα locus (PMID:31633019), and Treg homeostasis through direct physical interaction with FOXP3 (PMID:40183773). In meiosis, CDK1 drives cell-division-coupled inhibitory phosphorylation and degradation of CFP1 to clear it from chromosomes (PMID:30154440). CXXC1 physically interacts with the PRDM9 KRAB domain and meiotic axis/recombination factors (PMID:27932493), but two independent conditional knockouts show it is dispensable for PRDM9 hotspot H3K4me3, DSB formation, and male fertility, excluding it as the essential Spp1-like hotspot-to-DSB bridge in mouse spermatocytes (PMID:30365547).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2000 High

    Established the founding molecular activity—how CXXC1 reads the genome—by defining its CXXC domain as a sequence-specific reader of unmethylated CpG.

    Evidence EMSA, oligonucleotide competition, and reporter trans-activation with mutated/methylated CpG probes

    PMID:10688657 PMID:10799292

    Open questions at the time
    • Did not place CXXC1 in any chromatin-modifying complex
    • Full-length protein transactivation is autoinhibited; physiological regulator of de-repression unknown
  2. 2002 High

    Resolved where CXXC1 acts in the nucleus, showing it partitions to active euchromatin and the nuclear matrix via protein interactions rather than its DNA-binding domain.

    Evidence Immunofluorescence, nuclear matrix fractionation, and deletion-mutant co-localization with SC-35 and acetylated histones

    PMID:12200428

    Open questions at the time
    • Interaction partners driving speckle/matrix targeting not molecularly identified
    • Functional consequence of euchromatin restriction not yet tested genetically
  3. 2001 High

    Determined the developmental requirement for CXXC1, pinpointing an essential peri-implantation role distinct from early blastocyst formation.

    Evidence Germline knockout with histology and blastocyst outgrowth rescue mapping

    PMID:11604496

    Open questions at the time
    • Molecular cause of lethality not defined
    • No link yet to chromatin or DNA methylation
  4. 2005 High

    Connected CXXC1 to maintenance of global DNA methylation through DNMT1, revealing a second epigenetic axis beyond its DNA-reading role.

    Evidence ES cell knockout with bisulfite sequencing, methyltransferase assays, Western, and expression-vector rescue

    PMID:15923607

    Open questions at the time
    • Mechanism by which CXXC1 stabilizes DNMT1 not resolved
    • Relationship between methylation maintenance and H3K4me3 role not yet integrated
  5. 2009 High

    Defined CXXC1's core mechanistic identity as the SETD1A complex subunit that stabilizes the methyltransferase and restricts H3K4me3 to euchromatin.

    Evidence ES cell knockout with truncation/point-mutation structure-function and subnuclear localization readouts

    PMID:19951360

    Open questions at the time
    • Genome-wide targeting rules not yet mapped
    • Separation of DNA-binding versus complex-interaction contributions at endogenous loci not resolved
  6. 2014 Medium

    Mapped CXXC1 genomic occupancy to active (not bivalent) promoters, distinguishing SETD1-CXXC1 from MLL2-dependent H3K4me3.

    Evidence ChIP-seq in wild-type and Mll-knockout ES cells

    PMID:24423662 PMID:30292235

    Open questions at the time
    • Occupancy at enhancers and non-CGI TSS established only by correlation
    • No functional perturbation linking occupancy to transcription in these studies
  7. 2014 High

    Showed CXXC1 is a tissue-specific differentiation factor in hematopoiesis, required for HSPC differentiation but not stem-cell maintenance.

    Evidence Conditional (Mx1-Cre) knockout with bone marrow transplantation and flow cytometry

    PMID:25470594

    Open questions at the time
    • Direct target genes in HSPCs not identified
    • Link to H3K4me3 not directly profiled in this system
  8. 2016 High

    Identified direct CXXC1 target genes governing T-cell development and established epistasis upstream of RORγt.

    Evidence T-cell conditional knockout with CXXC1/H3K4me3 ChIP-seq and RORγt rescue

    PMID:27210293

    Open questions at the time
    • Whether all targets are direct SETD1-complex substrates not separated
    • Generalizability beyond thymocyte survival genes unclear
  9. 2017 High

    Tested the hypothesis that CXXC1 bridges PRDM9 hotspots to the meiotic DSB machinery, identifying physical links to PRDM9, cohesin, axis proteins, and IHO1.

    Evidence Yeast two-hybrid, in vitro binding, and co-IP from spermatocytes

    PMID:27932493 PMID:28527011

    Open questions at the time
    • Interactions did not demonstrate functional necessity in vivo
    • Y2H/in vitro binding not validated by loss-of-function at the time
  10. 2017 High

    Established CXXC1 as the SETD1 DNA-binding subunit required for oocyte H3K4me3, maturation, and developmental competence.

    Evidence Oocyte-specific conditional knockout with ChIP, immunofluorescence, and embryo development assays

    PMID:28768200

    Open questions at the time
    • Direct target genes underlying maturation failure not pinpointed
    • Cytoplasmic lattice defect mechanism not resolved
  11. 2018 High

    Refuted the Spp1-like hotspot-bridge model in mouse, showing CXXC1 is dispensable for PRDM9 hotspot H3K4me3, DSB formation, and male fertility.

    Evidence Two independent conditional knockouts with DMC1 and H3K4me3 ChIP-seq and fertility assays

    PMID:30365547

    Open questions at the time
    • Reconciliation with documented physical interactions not fully explained
    • Possible redundancy masking a role not excluded
  12. 2018 High

    Revealed cell-cycle control of CXXC1 in meiosis, with CDK1-driven phosphorylation and degradation clearing CFP1 from chromosomes for proper division.

    Evidence Oocyte conditional knockout plus pharmacological inhibition, overexpression, live imaging, and phospho-analysis

    PMID:30154440

    Open questions at the time
    • CDK1 phosphosites on CFP1 not enumerated
    • Degradation machinery not identified
  13. 2019 High

    Extended CXXC1's T-cell role to TH17/Treg balance via direct maintenance of H3K4me3 at the Il6rα locus and IL-6/STAT3 signaling.

    Evidence T-cell conditional knockout with ChIP-seq, IL-6Rα rescue, and in vivo EAE

    PMID:31633019

    Open questions at the time
    • Rescue only partial, implying additional targets
    • Direct versus indirect effects on STAT3 axis not fully separated
  14. 2019 High

    Demonstrated a cell-nonautonomous output of CXXC1-dependent H3K4me3, controlling oocyte paracrine signaling to granulosa cells and follicle growth.

    Evidence Oocyte conditional knockout with cumulus-cell transcriptomics, ovarian histology, and hormone signaling assays

    PMID:31676962

    Open questions at the time
    • Identity of the key paracrine factors not narrowed
    • Direct CXXC1 targets among paracrine genes not ChIP-validated
  15. 2020 High

    Defined CXXC1's meiotic requirement in spermatogenesis, linking H3K4me3 maintenance to transcriptional timing, DSB repair, and crossover formation.

    Evidence Stra8-Cre conditional knockout with H3K4me3/DMC1 ChIP-seq and meiotic spread analysis

    PMID:32094118

    Open questions at the time
    • Apparent tension with the negative fertility study (#13) regarding meiotic requirement not reconciled
    • Direct cause of crossover defect not isolated
  16. 2021 High

    Showed CXXC1 orchestrates multiple epigenetic layers in oocytes—H3K4me3, DNA methylation, H3K27me3, H2AK119ub1—and acts non-redundantly with MLL2.

    Evidence Oocyte conditional knockout with CUT&TAG and whole-genome bisulfite sequencing

    PMID:33621320

    Open questions at the time
    • Causal hierarchy among the affected marks not established
    • Direct versus secondary effects on H3K27me3/H2AK119ub1 unresolved
  17. 2021 Medium

    Extended CXXC1's CD4+ T-cell role to phase-specific late re-expression of TCR-modulated genes affecting Th1/Th2 programs and inflammation.

    Evidence T-cell conditional knockout with transcriptomics and in vivo airway inflammation

    PMID:33433611

    Open questions at the time
    • Direct binding to Trib3/Klf2 not shown by ChIP
    • Mechanism of temporal control of re-expression unknown
  18. 2022 Medium

    Linked CXXC1-maintained H3K4me3 to maternal mRNA translation/decay and an aging timer in oocytes.

    Evidence Oocyte conditional knockout with scRNA-seq and H3K4me3 profiling in young versus aged oocytes

    PMID:35680896

    Open questions at the time
    • Mechanistic coupling of H3K4me3 to mRNA decay competence not defined
    • Aging-associated CXXC1 decline is correlative
  19. 2025 High

    Identified a transcription-factor-directed mode of recruitment, with CXXC1 physically interacting with FOXP3 and co-occupying Treg program loci to set H3K4me3 and immunosuppressive function.

    Evidence Treg conditional knockout with co-IP, CUT&TAG for CXXC1/H3K4me3, and FOXP3 ChIP

    PMID:40183773

    Open questions at the time
    • Whether FOXP3 recruits CXXC1 or vice versa not resolved
    • Interaction interface not mapped
  20. 2025 Medium

    Showed conservation of CXXC1 function in zygotic genome activation, pre-marking CpG-dense hypomethylated loci with H3K4me3 for ZGA in Xenopus.

    Evidence Xenopus loss-of-function with developmental-stage H3K4me3 ChIP-seq and ZGA transcriptomics

    PMID:41419741

    Open questions at the time
    • Direct targets beyond Pou5f3.2 not delineated
    • Single ortholog system; mammalian ZGA generality not tested here
  21. 2025 Medium

    Implicated CXXC1/Set1C dependency in cancer, coupling H3K4me3 maintenance to MYC/E2F-driven proliferation in melanoma.

    Evidence CRISPR depletion in melanoma lines with H3K4me3 ChIP-seq, transcriptional profiling, and dependency mapping (preprint)

    PMID:41726895

    Open questions at the time
    • Preprint, single lab
    • Direct versus indirect effects on MYC/E2F programs not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CXXC1's intrinsic CpG-reading specificity is integrated with transcription-factor-guided recruitment (e.g., FOXP3) to achieve locus-selective H3K4me3, and how this is reconciled with its DNMT1-dependent DNA-methylation maintenance role, remains unresolved.
  • Relative contributions of CXXC DNA binding versus partner-TF recruitment at endogenous loci unquantified
  • Mechanism connecting H3K4me3 deposition to DNMT1 stability undefined
  • Structural basis of partner interactions not determined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 4 GO:0060090 molecular adaptor activity 2 GO:0140110 transcription regulator activity 2
Localization
GO:0000228 nuclear chromosome 2 GO:0005634 nucleus 2 GO:0005654 nucleoplasm 1
Pathway
R-HSA-1474165 Reproduction 3 R-HSA-168256 Immune System 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1266738 Developmental Biology 2
Partners
FOXP3IHO1PRDM9REC8SETD1ASYCP1SYCP3
Complex memberships
SETD1A/Set1C (COMPASS) H3K4 methyltransferase complex

Evidence

Reading pass · 26 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 CXXC domain fragment binds oligonucleotides containing a single CpG site, fails to bind when CpG is mutated or methylated, and does not bind single-stranded DNA or RNA. A single CpG dinucleotide introduced into an unrelated sequence is sufficient to create a binding site. Native hCGBP trans-activates CpG-containing promoters but not those lacking CpG. Ligand screening, electrophoretic mobility shift assay (EMSA), oligonucleotide competition assays, reporter gene trans-activation assays, Western analysis Molecular and cellular biology High 10688657
2000 CXXC1 (PCCX1) contains a PHD finger and a CXXC domain; the CXXC domain alone is sufficient for DNA binding. The acidic region confers transactivation, but the full-length protein is inactive because C-terminal regions inhibit the acidic domain. Proteolytic removal of the C-terminal inhibitory region activates the protein. Recombinant protein domain deletion/expression assays, transactivation reporter assays, Western analysis during cellular aging/immortalization Biochemical and biophysical research communications Medium 10799292
2002 CXXC1 (CGBP) localizes to nuclear speckles co-localizing with splicing factor SC-35 and acetylated histones (active chromatin/euchromatin), is excluded from metaphase chromosomes and heterochromatin. It associates with the nuclear matrix; fragments lacking nuclear matrix association also fail to localize to nuclear speckles and show reduced transcriptional activation. Punctate nuclear speckle localization requires signals in acidic, basic, and coiled-coil domains, not the DNA-binding domain, indicating protein–protein interactions drive subnuclear targeting. CGBP co-localizes with human trithorax, suggesting a common complex. Immunofluorescence/confocal microscopy, nuclear matrix fractionation, deletion mutant analysis, co-localization with SC-35 and acetylated histones The Journal of biological chemistry High 12200428
2001 Homozygous deletion of CXXC1 (CGBP) in mice results in embryonic lethality before 6.5 dpc. CGBP-null blastocysts are viable and can form inner cell mass and trophectoderm, establishing that CGBP is required for peri-implantation development (post-blastocyst stage) but not earlier. Homologous recombination knockout, histological examination, in vitro blastocyst outgrowth assay Molecular and cellular biology High 11604496
2005 CXXC1 (CGBP)-null embryonic stem cells show 60–80% reduction in global cytosine methylation, including hypo-methylation of repetitive elements, single-copy genes, and imprinted genes. Total DNA methyltransferase activity is reduced 30–60%, and DNMT1 protein levels are similarly reduced. De novo DNA methyltransferase activity is normal. Null cells are unable to differentiate and maintain pluripotency markers (Oct4, alkaline phosphatase). All phenotypes are rescued by re-introduction of a CGBP expression vector. ES cell knockout (homologous recombination), bisulfite sequencing, methyltransferase activity assays, Western blot, differentiation assays, rescue with expression vector Molecular and cellular biology High 15923607
2009 CXXC1 (CFP1) is a component of the euchromatic SETD1A (Setd1A) histone H3K4 methyltransferase complex. In Cfp1-null ES cells, SETD1A protein levels are decreased and both SETD1A and H3K4me3 mislocalize to heterochromatin. Either the N-terminal (aa 1–367) or C-terminal (aa 361–656) fragment of CFP1 can restore SETD1A levels, but full-length CFP1 is required to restrict SETD1A and H3K4me3 to euchromatin. Both DNA-binding activity and SETD1A complex interaction are required for proper genomic targeting. ES cell knockout, structure-function analysis with point mutations and truncation fragments, immunofluorescence for subnuclear localization, Western blot The FEBS journal High 19951360
2014 In mouse embryonic stem cells, the SETD1 complex subunit CXXC1 (Cxxc1) is primarily bound to active promoters but not to bivalent promoters (unlike MLL2). This indicates that active promoters rely on SETD1 complex (with CXXC1) for H3K4me3, whereas bivalent promoters rely on MLL2. ChIP-seq in wild-type and Mll2-knockout/Mll1-knockout ES cells, genomic occupancy mapping Development (Cambridge, England) Medium 24423662
2014 Conditional deletion of Cxxc1 in adult hematopoietic cells (Mx1-Cre system) causes failure of hematopoiesis, near-complete loss of lineage-committed progenitors and mature blood cells, elevated apoptosis, and death within two weeks. The Lin−Sca-1+c-Kit+ (LSK) stem/progenitor population persists and expands, indicating CXXC1 is specifically required for differentiation of hematopoietic stem and progenitor cells but not their maintenance. Bone marrow transplant confirmed the phenotype is cell-intrinsic. Conditional knockout (Mx1-Cre), bone marrow transplantation, flow cytometry, histology PloS one High 25470594
2016 CXXC1 directly controls expression of key thymocyte survival genes (RORγt) and T-cell receptor signaling genes (Zap70, CD8) by maintaining H3K4me3 at their promoters. Cxxc1-deficient mice show severely impaired T-cell development. RORγt overexpression rescues survival defects in Cxxc1-deficient thymocytes, placing CXXC1 upstream of RORγt in this pathway. T-cell-specific conditional Cxxc1 knockout, ChIP-seq for genome-wide CXXC1 binding and H3K4me3, rescue by RORγt overexpression, flow cytometry Nature communications High 27210293
2016 CXXC1 was identified as a direct interactor of the KRAB domain of PRDM9 in meiotic spermatocytes. This interaction was demonstrated by yeast two-hybrid assay, in vitro binding, and co-immunoprecipitation from mouse spermatocytes. CXXC1 also interacts with meiotic cohesin REC8 and synaptonemal complex proteins SYCP3/SYCP1, suggesting it links recombination hotspots to the chromosomal axis. Yeast two-hybrid assay, in vitro binding assay, co-immunoprecipitation from mouse spermatocytes Molecular biology of the cell High 27932493
2017 Oocyte-specific deletion of Cxxc1 (encoding CFP1, the DNA-binding subunit of SETD1 H3K4 methyltransferase) causes failure of H3K4me3 accumulation and defective deposition of histone variants onto chromatin. Cxxc1-null oocytes fail to complete maturation and are unable to gain developmental competence after fertilization due to defects in cytoplasmic lattice formation, meiotic division, and maternal-zygotic transition. Oocyte-specific conditional Cxxc1 knockout, ChIP, immunofluorescence, embryo development assays Cell reports High 28768200
2017 The KRAB domain of PRDM9 interacts with CXXC1 as demonstrated by yeast two-hybrid screens. CXXC1 in turn interacts with IHO1, a component of the meiotic double-strand break machinery. This positions CXXC1 as a potential molecular bridge between PRDM9-activated hotspots and the DSB machinery, analogous to yeast Spp1. Yeast two-hybrid assay Chromosoma Medium 28527011
2018 Oocyte-specific knockout of Cxxc1 causes a delay of meiotic resumption and metaphase I arrest due to defective spindle assembly and chromosome misalignment. These defects are partially attributed to insufficient phosphorylation of histone H3 at threonine-3. CDK1 triggers cell division-coupled degradation and inhibitory phosphorylation of CFP1; preventing CFP1 degradation causes its accumulation on chromosomes and impairs meiotic maturation and preimplantation embryo development. Oocyte-specific Cxxc1 knockout, CFP1 inhibitor treatment, live imaging, immunofluorescence, phosphorylation analysis Nature communications High 30154440
2018 NEGATIVE FINDING: Conditional knockout of Cxxc1 in mouse spermatocytes does not affect PRDM9 hotspot H3K4me3 trimethylation, double-strand break formation, or DSB repair, and male knockout mice are fertile. This demonstrates that CXXC1 is not an essential link between PRDM9-activated hotspot sites and the DSB machinery in mice, unlike its yeast ortholog Spp1. Two independent conditional Cxxc1 knockout mouse models (germ cell-specific and pre-meiotic), fertility assays, DMC1 ChIP-seq, H3K4me3 ChIP-seq PLoS genetics High 30365547
2018 CFP1 (CXXC1) occupies not only CpG island-associated active transcription start sites but also active non-CpG island TSSs and enhancers of transcribed genes in human haematopoietic cells. CFP1 occupancy at CGI promoters is mutually exclusive with H3K27me3 (Polycomb repressive mark). CpG-containing DNA motifs are enriched in CFP1 peaks at CGI promoters. ChIP-seq in two human haematopoietic cell types Epigenetics & chromatin Medium 30292235
2019 CXXC1 promotes TH17 cell generation and prevents Treg differentiation by binding to the Il6rα gene locus and maintaining H3K4me3 at its promoter, thereby sustaining IL-6Rα expression and IL-6/STAT3 signaling. Cxxc1-deficient T cells have decreased IL-6Rα expression; overexpression of IL-6Rα partially reverses TH17 differentiation defects in vitro and in vivo. T cell-specific Cxxc1 conditional knockout, ChIP-seq for genome-wide CXXC1 binding and H3K4me3, IL-6Rα overexpression rescue, in vivo EAE model Science advances High 31633019
2019 CFP1 (CXXC1)-dependent H3K4me3 in oocytes is required for the expression of key paracrine factors that mediate communication between oocytes and surrounding granulosa cells. Oocyte-specific Cxxc1 knockout disrupts gene expression in cumulus cells and impairs follicle growth and ovulation by indirectly compromising FSH and LH signaling pathways in granulosa cells—a cell-nonautonomous effect. Oocyte-specific Cxxc1 conditional knockout, transcriptome analysis of cumulus cells, ovarian histology, hormone signaling assays Cellular and molecular life sciences : CMLS High 31676962
2020 Meiosis-specific conditional deletion of Cxxc1 causes complete male sterility with spermatogenesis arrested at MII. Loss of CXXC1 decreases H3K4me3 from pachytene to MII, causes transcriptional disorder including premature expression of spermatogenesis genes (leading to abnormal acrosome formation), delays DSB repair, and causes improper crossover formation in pachytene cells. More than half of diplotene cells show precocious homologous chromosome segregation in both male and female meiosis. CXXC1 deletion also decreases H3K4me3 at DMC1-binding sites, potentially compromising DSB generation. Conditional Cxxc1 knockout (Stra8-Cre), ChIP-seq for H3K4me3 and DMC1, meiotic spread analysis, immunofluorescence for crossover markers Development (Cambridge, England) High 32094118
2021 Oocyte-specific Cxxc1 knockout impairs H3K4me3 accumulation genome-wide (promoter regions and gene bodies). CXXC1 and MLL2 have non-overlapping roles in H3K4 trimethylation during oogenesis. Cxxc1 deletion reduces DNA methylation levels and disrupts H3K27me3 and H2AK119ub1 distributions, particularly at high DNA methylation regions, indicating CXXC1 orchestrates multiple epigenetic layers in oocytes. Oocyte-specific conditional Cxxc1 knockout, CUT&TAG for H3K4me3/H3K27me3/H2AK119ub1, whole-genome bisulfite sequencing for DNA methylation Nucleic acids research High 33621320
2021 The CXXC1 subunit of the Trithorax complex directs transcription of a specific set of genes in CD4+ T cells that are initially downregulated by TCR stimulation but re-expressed in a later phase. Loss of CXXC1 impairs late upregulation of Trib3 (Th1) and Klf2 (Th2) and enhances pathogenicity in allergic airway inflammation in vivo. T cell-specific conditional Cxxc1 knockout, transcriptomic profiling, in vivo allergic airway inflammation model The Journal of experimental medicine Medium 33433611
2022 Oocyte-specific Cxxc1 knockout causes ooplasm changes associated with accelerated aging, and impairs maternal mRNA translation and degradation. CXXC1-maintained H3K4me3 is linked to mRNA decay competence and sets a timer for oocyte deterioration. H3K4me3 levels are high in fully grown oocytes from young females but decrease with age, correlating with decreased CXXC1 expression. Oocyte-specific conditional Cxxc1 knockout, transcriptome analysis (scRNA-seq), H3K4me3 profiling in young vs aged oocytes Nature communications Medium 35680896
2013 The CXXC domain of CGBP (CFP1/CXXC1) can bind unmethylated CpG-containing DNA in vitro with a distinct affinity compared to MLL and DNMT1 CXXC domains. When substituted for the MLL CXXC domain in the MLL-AF9 leukemogenic fusion protein, the CGBP CXXC domain abrogates colony-forming ability and leukemogenicity despite allowing targeting to the Hoxa9 locus, because it does not protect specific CpG residues at the Hoxa9 locus from methylation in the same manner as MLL CXXC. Domain swap experiments in MLL-AF9 fusion, in vitro DNA binding affinity assays, colony-forming assays, in vivo leukemogenesis, ChIP at Hoxa9 The Journal of biological chemistry Medium 23990460
2025 CXXC1 (CFP1) physically interacts with the transcription factor FOXP3 in regulatory T cells and co-occupies genomic regulatory regions of Treg program genes overlapping with FOXP3-binding sites. CXXC1 facilitates regulation of FOXP3 target genes by modulating H3K4me3 deposition at these loci. Cxxc1 deletion in Treg cells causes severe inflammatory disease and impaired immunosuppressive function. Treg-specific Cxxc1 conditional knockout, co-immunoprecipitation (CXXC1-FOXP3 interaction), CUT&TAG for H3K4me3 and CXXC1 genomic occupancy, ChIP for FOXP3 eLife High 40183773
2025 In Xenopus laevis, Cxxc1 ensures establishment of H3K4me3 at CpG-dense, DNA-hypomethylated loci in gametes and pre-ZGA embryos, and is required for proper zygotic genome activation (ZGA) including expression of the key ZGA transcription factor Pou5f3.2. H3K4me3 pre-marking at these loci is required for successful ZGA and development. Xenopus laevis Cxxc1 loss-of-function, H3K4me3 ChIP-seq across developmental stages, ZGA transcriptome analysis Nature communications Medium 41419741
2025 CXXC1 depletion in CXXC1-dependent melanoma cells reduces global H3K4me3 levels and inhibits proliferation. The Set1C/COMPASS dependency is linked to MYC- and E2F-driven transcriptional programs, which are suppressed upon CXXC1/complex inhibition. CRISPR genetic depletion of CXXC1 in melanoma cell lines, H3K4me3 ChIP-seq, transcriptional profiling, proliferation assays, integrative dependency mapping bioRxivpreprint Medium 41726895
2025 CRISPR knockout screen identified CXXC1 as essential for epidermal progenitor homeostasis and differentiation in human keratinocytes. Genome-wide CRISPR knockout screen of 1772 TFs in human epidermal cells Nature communications Low 40998781

Source papers

Stage 0 corpus · 53 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 Mll2 is required for H3K4 trimethylation on bivalent promoters in embryonic stem cells, whereas Mll1 is redundant. Development (Cambridge, England) 219 24423662
2000 Cloning of a mammalian transcriptional activator that binds unmethylated CpG motifs and shares a CXXC domain with DNA methyltransferase, human trithorax, and methyl-CpG binding domain protein 1. Molecular and cellular biology 154 10688657
2000 Mechanism of transcriptional regulation by methyl-CpG binding protein MBD1. Molecular and cellular biology 138 10866667
2004 Expression of mRNAs for DNA methyltransferases and methyl-CpG-binding proteins in the human female germ line, preimplantation embryos, and embryonic stem cells. Molecular reproduction and development 102 14735494
2017 CFP1 Regulates Histone H3K4 Trimethylation and Developmental Potential in Mouse Oocytes. Cell reports 84 28768200
2016 PRDM9 interactions with other proteins provide a link between recombination hotspots and the chromosomal axis in meiosis. Molecular biology of the cell 76 27932493
2001 CpG binding protein is crucial for early embryonic development. Molecular and cellular biology 76 11604496
2005 Reduced genomic cytosine methylation and defective cellular differentiation in embryonic stem cells lacking CpG binding protein. Molecular and cellular biology 74 15923607
2017 The PRDM9 KRAB domain is required for meiosis and involved in protein interactions. Chromosoma 66 28527011
2018 CFP1 coordinates histone H3 lysine-4 trimethylation and meiotic cell cycle progression in mouse oocytes. Nature communications 58 30154440
2009 CXXC finger protein 1 restricts the Setd1A histone H3K4 methyltransferase complex to euchromatin. The FEBS journal 52 19951360
2014 Extreme HOT regions are CpG-dense promoters in C. elegans and humans. Genome research 46 24653213
2009 Promoter CpG island hypermethylation- and H3K9me3 and H3K27me3-mediated epigenetic silencing targets the deleted in colon cancer (DCC) gene in colorectal carcinogenesis without affecting neighboring genes on chromosomal region 18q21. Carcinogenesis 44 19329758
2002 CpG-binding protein is a nuclear matrix- and euchromatin-associated protein localized to nuclear speckles containing human trithorax. Identification of nuclear matrix targeting signals. The Journal of biological chemistry 43 12200428
2015 Histone H3K4 trimethylation: dynamic interplay with pre-mRNA splicing. Biochemistry and cell biology = Biochimie et biologie cellulaire 42 26352678
2016 CXXC finger protein 1 is critical for T-cell intrathymic development through regulating H3K4 trimethylation. Nature communications 38 27210293
2020 The Gene-Regulatory Footprint of Aging Highlights Conserved Central Regulators. Cell reports 32 32997995
2018 Copper induces expression and methylation changes of early development genes in Crassostrea gigas embryos. Aquatic toxicology (Amsterdam, Netherlands) 32 29353135
2018 Alzheimer's disease DNA methylome of pyramidal layers in frontal cortex: laser-assisted microdissection study. Epigenomics 31 30324800
2020 CXXC finger protein 1-mediated histone H3 lysine-4 trimethylation is essential for proper meiotic crossover formation in mice. Development (Cambridge, England) 27 32094118
2014 The epigenetic regulator CXXC finger protein 1 is essential for murine hematopoiesis. PloS one 27 25470594
2003 MBD1, MBD2 and CGBP genes at chromosome 18q21 are infrequently mutated in human colon and lung cancers. Oncogene 27 12776203
2013 Functional specificity of CpG DNA-binding CXXC domains in mixed lineage leukemia. The Journal of biological chemistry 26 23990460
2019 Epigenetic initiation of the TH17 differentiation program is promoted by Cxxc finger protein 1. Science advances 24 31633019
2022 Dynamic mRNA degradome analyses indicate a role of histone H3K4 trimethylation in association with meiosis-coupled mRNA decay in oocyte aging. Nature communications 23 35680896
2019 CFP1-dependent histone H3K4 trimethylation in murine oocytes facilitates ovarian follicle recruitment and ovulation in a cell-nonautonomous manner. Cellular and molecular life sciences : CMLS 23 31676962
2001 Regulation of transcription and chromatin by methyl-CpG binding protein MBD1. Brain & development 23 11738867
2021 The Cxxc1 subunit of the Trithorax complex directs epigenetic licensing of CD4+ T cell differentiation. The Journal of experimental medicine 22 33433611
2021 Role of CxxC-finger protein 1 in establishing mouse oocyte epigenetic landscapes. Nucleic acids research 22 33621320
2018 CXXC1 is not essential for normal DNA double-strand break formation and meiotic recombination in mouse. PLoS genetics 20 30365547
2023 Cxxc finger protein 1 maintains homeostasis and function of intestinal group 3 innate lymphoid cells with aging. Nature aging 19 37429951
2022 Expression of the histone lysine methyltransferases SETD1B, SETDB1, SETD2, and CFP1 exhibits significant changes in the oocytes and granulosa cells of aged mouse ovaries. Histochemistry and cell biology 18 35445296
2018 CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands. Epigenetics & chromatin 18 30292235
2006 DNA sequence recognition by Hoechst 33258 conjugates of hairpin pyrrole/imidazole polyamides. Bioorganic & medicinal chemistry letters 13 16682192
2002 Cloning and characterization of the gene encoding the mouse homologue of CpG binding protein. Gene 12 12242013
2004 Identification and characterization of FBXL19 gene in silico. International journal of molecular medicine 10 15547684
1983 Interaction of ribulose bisphosphate carboxylase/oxygenase with 2-carboxyhexitol 1,6-bisphosphates. Archives of biochemistry and biophysics 10 6573158
2022 Orchestrating recombination initiation in mice and men. Current topics in developmental biology 9 36681473
2015 Genes Regulated by Vitamin D in Bone Cells Are Positively Selected in East Asians. PloS one 6 26719974
2023 The diagnostic significance of the ZNF gene family in pancreatic cancer: a bioinformatics and experimental study. Frontiers in genetics 5 37396042
1990 Effects of DNA and synthetic oligodeoxyribonucleotides on the binding properties of a cGMP-binding protein from Dictyostelium discoideum. Biochimica et biophysica acta 5 2169308
2000 PCCX1, a novel DNA-binding protein with PHD finger and CXXC domain, is regulated by proteolysis. Biochemical and biophysical research communications 4 10799292
1996 A tobacco nuclear protein that preferentially binds to unmethylated CpG-rich DNA. European journal of biochemistry 4 8654405
2025 Disease-linked regulatory DNA variants and homeostatic transcription factors in epidermis. Nature communications 2 40998781
2025 Pre-marking chromatin with H3K4 methylation is required for accurate zygotic genome activation and development. Nature communications 2 41419741
2025 Analysis of DNA methylation changes following Cfp1 knockout in mouse spermatocytes. Animal bioscience 1 40045604
2023 The Effects of Larval Cryopreservation on the Epigenetics of the Pacific Oyster Crassostrea gigas. International journal of molecular sciences 1 38139089
2026 Systematic multivariate analysis of chromatin complex dependencies reveals Set1C/COMPASS as a melanoma-enriched epigenetic vulnerability. bioRxiv : the preprint server for biology 0 41726895
2026 Ythdf2/Setd1b regulatory axis is essential for cerebellar development through regulating epigenetic reprogramming. Molecular psychiatry 0 41933071
2025 CXXC-finger protein 1 associates with FOXP3 to stabilize homeostasis and suppressive functions of regulatory T cells. eLife 0 40183773
2024 Disease-Linked Regulatory DNA Variants and Homeostatic Transcription Factors in Epidermis. bioRxiv : the preprint server for biology 0 39605549
2019 [Preparation of anti-hCG antibody-like molecule by using a RAD peptide display system]. Sheng wu gong cheng xue bao = Chinese journal of biotechnology 0 31223005
2017 [The sequence coverage in different methods of mass spectrometry data analysis obtained on model proteins]. Biomeditsinskaia khimiia 0 29080871

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