Affinage

Showing CTCFL — BORIS is a alias.

CTCFL

Transcriptional repressor CTCFL · UniProt Q8NI51

Length
663 aa
Mass
75.7 kDa
Annotated
2026-06-09
100 papers in source corpus 43 papers cited in narrative 43 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CTCFL (BORIS) is a testis-restricted paralog of CTCF that shares an identical 11-zinc-finger DNA-binding domain encoded by the same exons but carries divergent N- and C-termini, and it is expressed in a mutually exclusive pattern with CTCF during male germ-cell epigenetic reprogramming (PMID:12011441). Its terminal segments are intrinsically disordered, providing a structural basis for paralog-specific cofactor recruitment that distinguishes it from CTCF (PMID:20438700). CTCFL and CTCF co-occupy a subset of clustered CTCF target sites (2xCTSes) found at active promoters and enhancers, and the two proteins act combinatorially to repress pre-meiotic genes and activate post-meiotic spermatogenesis programs; combined depletion in mice causes male sterility, defective meiotic recombination, and germ-cell death (PMID:26268681, PMID:34158481). Site selection by CTCFL is governed by chromatin state rather than methylation: it is targeted to open chromatin marked by H3K27ac, H3K4me2/3 and H2A.Z and to loosely assembled nucleosomes, and unlike CTCF it lacks the N-terminal cohesin-interaction module required for canonical loop formation (PMID:22709888, PMID:29860503, PMID:32393311). Mechanistically, CTCFL functions as a chromatin remodeler that recruits the SRCAP complex to exchange H2A for H2A.Z and relax flanking nucleosomes, converting intergenic and intronic CTCF sites into active de novo promoters that drive cancer-testis genes, lncRNAs, and dormant transposable elements (PMID:38297316). It also stimulates PRMT7-catalyzed symmetric H4R3 dimethylation during germ-cell imprint establishment (PMID:17048991), and in cancer cells it reactivates silenced loci such as MAGE-A1 and NY-ESO-1 through a CTCF-to-BORIS occupancy switch and chromatin opening (PMID:16140943, PMID:16140944, PMID:21558405). Beyond transcription, CTCFL binds intragenic methylated DNA to control alternative splicing—promoting cancer-specific PKM2 splicing and the Warburg effect—is an RNA-binding protein that co-fractionates with translating polysomes, and undergoes DNA-damage-induced ADP-ribosylation that recruits Ku70 for DNA damage repair (PMID:29073069, PMID:24279897, PMID:35918747). In neuroblastoma it remodels chromatin looping to generate super-enhancers driving drug resistance (PMID:31391581).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2002 High

    Established that CTCFL is a distinct, testis-specific CTCF paralog rather than a redundant copy, defining the central puzzle of two proteins sharing a DNA-binding domain but separated in space and time.

    Evidence Molecular cloning, sequence analysis, and testis expression profiling against CTCF

    PMID:12011441

    Open questions at the time
    • Did not define genome-wide binding differences from CTCF
    • Mechanism of mutually exclusive expression not resolved
  2. 2002 Medium

    First evidence that CTCFL and CTCF have antagonistic effects on proliferation, framing CTCFL as a potential growth-promoting/transforming factor.

    Evidence Ectopic expression in somatic cell lines with proliferation assays

    PMID:12191639

    Open questions at the time
    • No molecular mechanism for growth promotion
    • Later work (#18) challenged the simple oncogenic model
  3. 2005 High

    Showed that a CTCF-to-BORIS occupancy switch at methylation-insensitive 11ZF sites reactivates silenced cancer-testis genes (MAGE-A1, NY-ESO-1), linking paralog switching to epigenetic derepression.

    Evidence Conditional BORIS expression, reciprocal ChIP, bisulfite sequencing, shRNA rescue in fibroblasts and lung cancer cells

    PMID:16140943 PMID:16140944

    Open questions at the time
    • Chromatin remodeling machinery recruited by BORIS not yet identified
    • Generality across the genome untested
  4. 2006 High

    Identified PRMT7 as a CTCFL cofactor, providing a histone-modification mechanism (symmetric H4R3 dimethylation) linking CTCFL to germline imprint establishment.

    Evidence Co-IP, in vitro histone methyltransferase assay, and Xenopus oocyte reconstitution of H19 ICR methylation

    PMID:17048991

    Open questions at the time
    • Endogenous requirement for CTCFL-PRMT7 in mammalian imprinting not shown
    • Direct genomic targets of the complex undefined
  5. 2007 Medium

    Defined how BORIS is itself controlled, showing alternative promoters repressed by DNA methylation, p53, and CTCF, and identifying Sp1 as a recruited transcriptional partner at target promoters.

    Evidence 5' RACE, promoter-reporter assays, CTCF knockdown, co-IP and ChIP for Sp1

    PMID:17260018 PMID:17962299

    Open questions at the time
    • Single-lab promoter dissection
    • Sp1 interaction not tested genome-wide
  6. 2008 High

    Resolved the methylation question by showing BORIS binds methylated DNA (including the methylated paternal H19 DMR) while CTCF prefers unmethylated DNA, distinguishing the paralogs biochemically.

    Evidence EMSA with in vitro translated protein, methylation-specific and allele-specific ChIP in murine hybrid cells

    PMID:18632606

    Open questions at the time
    • Reconciliation with methylation-insensitive sites (#2,#3) left open
    • Structural basis of methylated-DNA preference unknown
  7. 2010 High

    Linked BORIS to a germline gene program in vivo, showing it activates testis-specific genes and that its loss causes subfertility and germ-cell death.

    Evidence BORIS knockout mice, expression profiling, ChIP, and promoter mutagenesis for Gal3st1/CST

    PMID:20231363

    Open questions at the time
    • Partial penetrance suggested redundancy not yet explained
    • Cofactors driving activation in vivo not identified
  8. 2010 Medium

    Demonstrated functional diversity of BORIS through 23 nuclear isoforms with variable zinc-finger composition, showing N-terminal identity and DNA binding jointly determine transcriptional activation.

    Evidence RT-PCR isoform characterization, EMSA, and isoform-specific reporter assays

    PMID:21079786

    Open questions at the time
    • Physiological roles of individual isoforms unresolved
    • Single-lab characterization
  9. 2012 High

    Established chromatin-state, not methylation alone, as the determinant of CTCFL versus CTCF targeting, with CTCFL favoring loosely assembled nucleosomes and being functionally non-interchangeable with CTCF.

    Evidence CTCFL KO mice, genome-wide ChIP-seq, and ES-cell rescue assay

    PMID:22709888

    Open questions at the time
    • Remodeler responsible for the loose-nucleosome state not yet identified
    • Mechanism of distinct site targeting incompletely defined
  10. 2012 Medium

    Connected BORIS to cell-cycle progression, transcription, and genomic instability, and localized it to nucleolus and centrosomes with accumulation upon S-phase arrest and DNA damage.

    Evidence Immunofluorescence, nascent RNA labeling, live-cell imaging, and shRNA knockdown in keratinocytes

    PMID:22724006

    Open questions at the time
    • Centrosomal/nucleolar functions not mechanistically dissected
    • Link between DNA damage accumulation and repair not established here
  11. 2015 High

    Defined the genomic logic of paralog co-occupancy: CTCFL and CTCF share clustered 2xCTSes enriched at active promoters/enhancers, and BORIS perturbation reprograms transcription and differentiation.

    Evidence Genome-wide ChIP-seq with loss- and gain-of-function in K562 and MCF7 cells

    PMID:26268681

    Open questions at the time
    • Mechanism converting 2xCTSes to active promoters not yet defined
    • Cofactor recruitment at 2xCTSes unknown
  12. 2017 High

    Extended BORIS function to co-transcriptional RNA processing, showing intragenic methylation-dependent binding controls cancer-specific PKM2 splicing and the Warburg effect.

    Evidence siRNA depletion, CRISPR/Cas9 binding-site deletion, splicing RT-PCR, and metabolic assays in breast cancer cells

    PMID:29073069

    Open questions at the time
    • Splicing machinery recruited by BORIS not identified here
    • Breadth of methylation-dependent splicing targets only partly mapped
  13. 2017 Medium

    Identified TAF7L as a germ-cell-specific BORIS partner and placed BORIS-bound 2xCTSes at highly expressed germ-cell genes with histone retention in spermatozoa.

    Evidence Co-IP and ChIP-seq in mouse germ cells with histone-retention analysis

    PMID:28145452

    Open questions at the time
    • Functional consequence of TAF7L interaction untested
    • Single-lab co-IP
  14. 2019 High

    Demonstrated that BORIS reshapes 3D chromatin to form super-enhancers, driving an ALK-inhibitor-resistance transcriptional program in MYCN-amplified neuroblastoma.

    Evidence Hi-C, ChIP-seq, RNA-seq, and overexpression/depletion in a resistance model

    PMID:31391581

    Open questions at the time
    • Mechanism by which BORIS nucleates new loops without cohesin module unclear
    • Whether looping is direct or downstream of transcription not resolved
  15. 2020 High

    Pinpointed the molecular reason CTCFL cannot replace CTCF in loop formation: the CTCF N-terminus binds cohesin while CTCFL lacks it, with each domain contributing to paralog-specific targeting.

    Evidence Inducible complementation with CTCF-CTCFL chimeras, ChIP-seq, and Hi-C ± endogenous CTCF

    PMID:32393311

    Open questions at the time
    • How CTCFL still promotes looping in some contexts (#28) not reconciled
    • Cofactors bound by the divergent CTCFL termini not fully enumerated
  16. 2021 High

    Showed CTCF and BORIS heterodimerize and act combinatorially to control the meiotic-to-postmeiotic gene switch, with loss of both causing sterility and CTCF binding lost preferentially from heterodimeric sites.

    Evidence Compound mutant mice with graded CTCF/BORIS levels, ChIP-seq, RNA-seq, fertility and histology

    PMID:34158481

    Open questions at the time
    • Stoichiometry and structural basis of heterodimerization not defined
    • Direct versus indirect target effects not fully separated
  17. 2022 High

    Revealed a non-transcriptional role in genome maintenance: DNA-damage-induced ADP-ribosylation of conserved glutamates licenses BORIS-Ku70 interaction and DNA repair.

    Evidence Site-directed mutagenesis, peptide inhibitor (BTApep-TAT), co-IP, γH2AX assay, and xenograft model

    PMID:35918747

    Open questions at the time
    • Identity of the ADP-ribosyltransferase not established
    • Repair pathway placement (NHEJ vs other) only inferred via Ku70
  18. 2024 High

    Delivered the unifying chromatin-remodeling mechanism: BORIS recruits SRCAP to deposit H2A.Z and relax nucleosomes, converting silent CTCF sites into active de novo promoters for cancer-testis genes and repeats.

    Evidence ChIP-seq, ATAC-seq, H2A.Z ChIP, RNA-seq, and BORIS-SRCAP co-IP with depletion/overexpression

    PMID:38297316

    Open questions at the time
    • Whether SRCAP recruitment explains all BORIS-activated loci untested
    • Connection to the disordered termini (#40) not directly demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How CTCFL integrates its multiple activities—chromatin remodeling, methylation-dependent splicing, RNA binding, and DNA-damage repair—into a single coherent cellular program, and how its divergent disordered termini route it among these functions, remains unresolved.
  • No structural model linking disordered termini to specific cofactor choices
  • Relative contribution of each activity to germ-cell versus cancer phenotypes unclear
  • No reconstitution of full SRCAP-dependent promoter conversion in vitro

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003677 DNA binding 5 GO:0140110 transcription regulator activity 5 GO:0003723 RNA binding 1 GO:0042393 histone binding 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 1 GO:0005815 microtubule organizing center 1 GO:0005840 ribosome 1
Pathway
R-HSA-1474165 Reproduction 3 R-HSA-4839726 Chromatin organization 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-8953854 Metabolism of RNA 3 R-HSA-73894 DNA Repair 1
Partners
CTCFKU70PRMT7SP1SRCAPSRSF6TAF7L

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 CTCFL/BORIS is a paralog of CTCF sharing the same 11-zinc-finger DNA-binding domain (encoded by identical exons) but with distinct amino and carboxy termini; it is expressed exclusively in testis in a mutually exclusive pattern with CTCF during male germ cell development, coinciding with erasure of methylation marks during epigenetic reprogramming. Molecular cloning, sequence analysis, Northern/Western blot, expression profiling in testis Proceedings of the National Academy of Sciences of the United States of America High 12011441
2002 Overexpression of BORIS in normally BORIS-negative somatic cells promotes cell growth and can lead to transformation, whereas CTCF overexpression blocks cell proliferation, demonstrating antagonistic functional roles. Ectopic expression in somatic cell lines, cell proliferation assays Seminars in cancer biology Medium 12191639
2005 Conditional expression of BORIS in normal fibroblasts causes switching from CTCF to BORIS occupancy at an 11ZF target site in the MAGE-A1 promoter (a site insensitive to CpG methylation), leading to demethylation and transcriptional activation of MAGE-A1 and other cancer-testis genes; anti-BORIS shRNA prior to 5-azadC treatment blocked MAGE-A1 reactivation. Conditional BORIS expression, ChIP, bisulfite sequencing, shRNA knockdown, reporter assays Cancer research High 16140943
2005 BORIS binds a novel CTCF/BORIS-binding site in the NY-ESO-1 promoter (insensitive to CpG methylation in vitro); in vivo, CTCF occupancy correlates with NY-ESO-1 silencing while switching from CTCF to BORIS occupancy coincides with NY-ESO-1 derepression in lung cancer cells. Gel-shift assay, ChIP, bisulfite sequencing, methylation-specific PCR, co-transfection reporter assays Cancer research High 16140944
2006 CTCFL/BORIS interacts with PRMT7 (a protein arginine methyltransferase) and stimulates PRMT7's histone-methyltransferase activity via interactions with both histones and PRMT7; symmetrical dimethyl arginine 3 of histone H4 (catalyzed by PRMT7) accumulates in germ cells during ICR methylation. Nuclear co-injection of CTCFL, PRMT7, Dnmt3a, Dnmt3b, and DnmtL expression vectors in Xenopus oocytes was sufficient to drive H19 ICR methylation. Co-immunoprecipitation, in vitro histone methyltransferase assay, ChIP, Xenopus oocyte co-injection PLoS biology High 17048991
2007 BORIS expression is regulated by three alternative promoters (A, B, C) that are negatively regulated by DNA methylation and by functional p53; reduction of CTCF in normally BORIS-negative fibroblasts leads to derepression of BORIS promoters, establishing CTCF as a transcriptional repressor of BORIS. 5' RACE, promoter-reporter assays, bisulfite sequencing, CTCF knockdown Nucleic acids research Medium 17962299
2007 BORIS physically interacts with Sp1 (but not with CTCF) in vivo, and BORIS recruits Sp1 to the proximal Sp1-binding site of the NY-ESO-1 promoter to mediate its derepression in lung cancer cells. Co-immunoprecipitation, ChIP, gel-shift assay, siRNA knockdown, promoter-reporter assays Oncogene Medium 17260018
2008 CTCFL/BORIS is a methylation-independent DNA-binding protein; ChIP and EMSA using whole-cell extracts and in vitro translated protein showed BORIS binds methylated DNA while CTCF preferentially binds unmethylated DNA. In murine hybrid cells, BORIS preferentially binds the methylated paternal H19 differentially methylated region. ChIP, EMSA with in vitro translated protein, methylation-specific ChIP-PCR, murine hybrid cell system Cancer research High 18632606
2008 DNA methyltransferases DNMT1 and DNMT3B activate BAG-1 expression by recruiting CTCFL/BORIS to the BAG-1 promoter, which is associated with a permissive dimethyl-H3K4/dimethyl-H3K9 chromatin state; BORIS shRNA knockdown decreased BORIS promoter binding and BAG-1 expression and shifted the chromatin to a non-permissive state. ChIP, shRNA knockdown, DNMT-overexpressing and knockout cell lines Cancer research Medium 18413740
2010 BORIS binds to and activates the testis-specific CST (Gal3st1 form F_TS) promoter; mutation of the BORIS binding site in the promoter abrogated BORIS binding and activation. BORIS knockout mice showed reduced CST expression, delayed haploid cell production, and increased germ cell death. BORIS knockout mice, gene expression profiling, ChIP, promoter-reporter assay with binding site mutagenesis Molecular and cellular biology High 20231363
2010 Exogenous BORIS expression in normal BORIS-negative cells is sufficient to activate hTERT transcription; both CTCF and BORIS bind the first exon of hTERT in vivo in cancer cells, and BORIS counteracts the inhibitory effect of CTCF on hTERT. Ectopic BORIS expression, ChIP, quantitative RT-PCR Nucleic acids research Medium 20876690
2010 BORIS is expressed as 23 isoforms with alternative N- and C-termini and varying zinc finger numbers; all isoforms are translated and localize to the nucleus. Binding to DNA targets is methylation-sensitive and depends on the number and composition of zinc fingers; a specific long N-terminus (N258) combined with DNA-binding ability is necessary and sufficient for transcriptional activation of CST. RT-PCR isoform characterization, western blot, nuclear localization assay, EMSA, reporter assays with isoform-specific constructs PloS one Medium 21079786
2011 BORIS directly binds two conserved binding sites in the TSP50 promoter in a methylation-independent but nucleosome-occupancy-dependent manner and activates TSP50 transcription; mutation of binding sites abolished BORIS binding and promoter activation. ChIP, EMSA, promoter-reporter assay with binding site mutagenesis, DNase I sensitivity assay The Journal of biological chemistry High 21659515
2011 BORIS binds to the promoters of MAGEA2, MAGEA3, and MAGEA4 and activates their expression by inducing a shift to open chromatin; MAGEA3 activation involved promoter demethylation while MAGEA2 and MAGEA4 activation was independent of promoter demethylation. Doxycycline-inducible BORIS expression, ChIP, luciferase reporter assay, bisulfite sequencing, siRNA knockdown Clinical cancer research Medium 21558405
2011 BORIS binds to the intronic ferT promoter and is required for FerT expression in colorectal cancer cells; BORIS knockdown significantly decreases ferT expression and correlates with hypomethylation of the ferT promoter. ChIP, siRNA knockdown, bisulfite sequencing, RT-PCR The Journal of biological chemistry Medium 22223638
2012 CTCFL is expressed only transiently in spermatogonia and preleptotene spermatocytes, colocalizing with CTCF; absence of CTCFL causes subfertility with partially penetrant testicular atrophy and reduced expression of testis-specific genes (Gal3st1, Prss50). CTCFL binds promoters with loosely assembled nucleosomes whereas CTCF favors sites with phased nucleosomes. An ES cell rescue assay shows CTCFL is functionally distinct from CTCF. Immunohistochemistry, live-cell fluorescence microscopy, CTCFL KO mice, genome-wide RNA expression, genome-wide ChIP-seq, ES cell rescue assay Epigenetics & chromatin High 22709888
2012 BORIS localizes to the nucleolus (within nucleolin core structure, adjacent to fibrillarin) and to interphase centrosomes in keratinocytes; endogenous BORIS is present at active transcription sites. Blocking cell cycle at S phase or causing DNA damage produces striking BORIS accumulation. Ectopic BORIS expression increases S-phase cells and causes genomic instability; BORIS shRNA inhibits RNA transcription and cell cycle progression. Immunofluorescence, nascent RNA labeling, live-cell GFP imaging, cell cycle analysis, shRNA knockdown PloS one Medium 22724006
2012 Dose-dependent BORIS expression induces SBSN activation at low concentrations via CpG island demethylation and chromatin opening at the SBSN TSS, while higher BORIS concentrations suppress SBSN via chromatin repression; increasing BORIS also reduces cell growth and colony formation in a dose-dependent manner. Doxycycline-inducible BORIS expression, bisulfite sequencing, ChIP, RT-PCR, colony formation assay PloS one Medium 22792300
2013 Both BORIS and CTCF cause significant decrease in cell proliferation and clonogenic capacity and suppress breast cancer growth in an orthotopic model in vivo; both confer protective effects during UV-induced apoptosis in primary cells, challenging the simple oncogenic model for BORIS. Inducible lentiviral expression, cell proliferation assay, clonogenic assay, bioluminescent orthotopic mouse model International journal of cancer Medium 23553099
2013 BORIS/CTCFL is an RNA-binding protein; it associates with mRNA in neural stem cells and neurons, and co-fractionates with actively translating polysomes. The majority of BORIS-associated transcripts differ between cell types. BORIS contains a putative nuclear export signal in the C-terminal domain. RNA immunoprecipitation, polysome profiling, domain analysis BMC cell biology Medium 24279897
2014 BORIS and Sp1 have opposing effects on MAGE-A1 promoter activity; both BORIS and Sp1 interact with the TATA-binding protein (hTBP), suggesting competitive regulation. Sp1 partially represses BORIS-mediated stimulation of the MAGE-A1 promoter. Ectopic BORIS also activates transcription from its own locus, inducing all splice variants. Luciferase reporter assays, ChIP, GST pull-down, quantitative RT-PCR, bisulfite sequencing BMC cancer Medium 25363021
2015 CTCFL and CTCF co-occupy a specific subset of regulatory elements with clustered CTCF binding motifs (2xCTSes); 2xCTSes are preferentially found at active promoters and enhancers in cancer and germ cells. BORIS depletion in K562 cells alters transcription of many genes and induces differentiation; ectopic BORIS in MCF7 cells induces specific transcriptional changes. Genome-wide ChIP-seq, BORIS depletion (siRNA/shRNA), ectopic expression, gene expression profiling Genome biology High 26268681
2016 BORIS binds preferentially to the VNTR region of SVA transposable elements in vivo (distinct from CTCF binding to the CTCF motif); RNA-seq shows BORIS largely represses SVA expression alongside DNA and histone methylation, with exception of promoter capture by SVA. ChIP-chip, ChIP-seq, RNA-seq Epigenetics & chromatin Medium 27588042
2017 Intragenic DNA methylation at the PKM alternative exon enables BORIS binding, which promotes cancer-specific PKM2 splicing and the Warburg effect; BORIS depletion or deletion of the BORIS binding site by CRISPR/Cas9 switches splicing from PKM2 to PKM1, reversing the Warburg effect and inhibiting breast cancer cell growth. BORIS also regulates alternative splicing of several other genes in a DNA methylation-dependent manner. BORIS depletion (siRNA), CRISPR/Cas9 binding site deletion, RT-PCR for splicing isoforms, metabolic assays, cell growth assays, bisulfite sequencing Proceedings of the National Academy of Sciences of the United States of America High 29073069
2017 BORIS binds near the TGFB1 promoter, coinciding with increased TGFB1 expression, and promotes a switch from a proliferative to an invasive phenotype in melanoma cells; inducible BORIS overexpression reduces proliferation and increases migration and invasion. Inducible BORIS overexpression, whole-transcriptome analysis (RNA-seq), ChIP, migration/invasion assays Cell death discovery Medium 32123577
2017 BORIS up-regulates OCT4 via histone methylation: BORIS binding at the OCT4 promoter increases H3K4me2 and reduces H3K27me3, without affecting DNA methylation at the OCT4 promoter. BORIS overexpression promotes cancer stem cell-like properties in liver cancer cells. ChIP, bisulfite sequencing, BORIS overexpression and knockdown, sphere formation and tumor-initiating assays Cancer letters Medium 28645561
2017 BORIS activates the TGFB1 pathway in neuroblastoma; BORIS stabilizes SMAD3 and SMAD4 transcripts, and loss of BORIS abrogates both canonical and non-canonical TGFβ signaling. Ectopic BORIS expression also induces Drp1 phosphorylation (Ser616), promoting mitochondrial fission and a metabolic switch toward glycolysis. BORIS overexpression and knockdown, RT-PCR, western blot (pathway components), oxygen consumption rate measurement Free radical biology & medicine Medium 34534628
2018 CTCFL binding site selection versus CTCF is driven by chromatin state: CTCFL is enriched at open chromatin marked by H3K27ac, H3K4me2/3, H3K79me2, H3K9ac, and H2A.Z, particularly at TSS regions. Specific nucleotide positions in the binding motif are critical for CTCFL but not CTCF binding. ChIP-seq, ATAC-seq, motif analysis, genome-wide binding comparison Nucleic acids research Medium 29860503
2019 BORIS promotes chromatin looping interactions in ALK-inhibitor-resistant, MYCN-amplified neuroblastoma cells; resistance is accompanied by loss of MYCN expression followed by BORIS overexpression. BORIS-regulated alterations in chromatin looping form super-enhancers that drive ectopic expression of proneural transcription factors defining the resistance phenotype. Hi-C/chromatin conformation capture, ChIP-seq, BORIS overexpression and depletion, RNA-seq, resistance model development Nature High 31391581
2019 BORIS expression in fallopian tube secretory epithelial cells (FTSEC) increases motility and invasion, and induces GALNT14 (a glycosyltransferase implicated in cancer cell migration); GALNT14 knockdown significantly abrogates BORIS-induced motility and invasion. BORIS expression is also associated with de novo and enhanced CTCF binding at hundreds of loci correlated with transcriptional activation. Lentiviral BORIS expression in FTSEC, migration/invasion assays, siRNA knockdown of GALNT14, RNA-seq, ChIP-seq Molecular cancer research Medium 31292201
2019 MAGEA1 interacts with CTCF to form a protein complex with DNMT3a; this complex binds the BORIS promoter, recruits DNMT3a, and causes hypermethylation and repression of BORIS expression. The MAGEA1-CTCF interaction is required for DNMT3a recruitment. Co-immunoprecipitation, GST pull-down, co-localization assay, ChIP, bisulfite sequencing, siRNA knockdown Journal of cell science Medium 30498011
2020 The N-terminus of CTCF (not shared by CTCFL) interacts with cohesin, explaining why convergent CTCF binding sites are required for loop formation; CTCFL lacks this N-terminal cohesin interaction and therefore cannot mediate the same chromatin loops as CTCF. CTCF and CTCFL have phenotypically distinct binding sites; N, C, and zinc finger domains each play unique roles in targeting each paralog to distinct sites. Inducible complementation system expressing CTCFL and CTCF-CTCFL chimeras ± endogenous CTCF, ChIP-seq, Hi-C, RNA-seq Genome biology High 32393311
2021 BORIS heterodimerizes with CTCF and combined depletion of both CTCF and BORIS (Ctcf+/-Boris-/- compound mutant mice) causes male sterility with reduced testes size, defective meiotic recombination, increased apoptosis, and malformed spermatozoa; chromatin binding of CTCF is preferentially lost from CTCF-BORIS heterodimeric sites. Combined action is required to repress pre-meiotic genes and activate post-meiotic spermatogenesis genes. Mouse genetic models (compound mutants with varied CTCF/BORIS levels), ChIP-seq, RNA-seq, fertility assays, histology Nature communications High 34158481
2021 CTCFL expression during mouse embryogenesis dysregulates the TGFβ pathway; transcriptome sequencing of Ctcfl-expressing ES cells revealed 14 deregulated genes with TGFβ pathway as most affected, and Ctcfl-expressing embryos show growth retardation, eye malformations, vascular defects, and neonatal death. Tetracycline-inducible transgenic mice, ES cell-tetraploid chimeras, RNA-seq, bioinformatic pathway analysis Molecular and cellular biology Medium 26169830
2022 BORIS undergoes ADP ribosylation at five conserved glutamic acid residues (E198–E228) upon DNA double- or single-strand damage; this modification is required for BORIS interaction with Ku70 and for BORIS function in DNA damage repair. Inhibiting ADP ribosylation (by site-specific mutation or by BTApep-TAT peptide) blocks BORIS-Ku70 interaction and impairs DNA damage repair. Phage display peptide inhibitor (BTApep-TAT), site-directed mutagenesis, co-immunoprecipitation, γH2AX assay, RNA-seq, xenograft mouse model Molecular cancer High 35918747
2022 HNF4A directly binds the BORIS promoter and negatively regulates BORIS expression; BORIS in turn directly binds the GLUT4 promoter and positively regulates GLUT4 expression, promoting hepatoma cell motility and metastasis in low-glucose conditions (AMPKα2/HNF4A/BORIS/GLUT4 pathway). ChIP, overexpression and knockdown complementation experiments, bioinformatic analysis, invasion/metastasis assays Biochemical pharmacology Medium 35940258
2024 BORIS/CTCFL epigenetically reprograms intergenic and intronic CTCF binding sites (2xCTSes) into active de novo promoters by recruiting the chromatin remodeling factor SRCAP, causing replacement of H2A with H2A.Z and relaxation of flanking nucleosomes; this facilitates recruitment of additional transcription factors and activates cancer-testis gene expression, lncRNAs, retro-pseudogenes, and dormant transposable elements. ChIP-seq, ATAC-seq, RNA-seq, co-immunoprecipitation (BORIS-SRCAP interaction), H2A.Z ChIP, BORIS depletion and overexpression Genome biology High 38297316
2024 BORIS binds methylated BNIP3L intron 1 under normoxia (while CTCF binds unmethylated intron 1 under hypoxia); BORIS binding causes RNA Pol-II pausing and recruits SRSF6, redirecting proximal splice-site selection to exclude exon 1 from BNIP3L mRNA (generating BNIP3L-Δ1 isoform), thereby inhibiting autophagy. ChIP (CTCF, BORIS, RNA Pol-II), bisulfite sequencing, RT-PCR splicing assay, siRNA knockdown, SRSF6 interaction assays The Journal of biological chemistry Medium 38810696
2017 BORIS physically interacts with TBP-associated factor 7-like (TAF7L) in germ cells; BORIS-bound 2xCTS regions are co-occupied by multiple testis-specific transcriptional regulators and are associated with highly expressed germ cell-specific genes and histone retention in mature spermatozoa. Co-immunoprecipitation (BORIS-TAF7L), ChIP-seq in mouse germ cells, histone retention analysis Scientific reports Medium 28145452
2008 DNA damage-induced upregulation of miR-709 in mouse testis (via ATR/Rfx1 signaling) targets BORIS mRNA and decreases BORIS protein levels, acting as a protective mechanism to prevent aberrant erasure of DNA methylation after radiation exposure. MicroRNA microarray, quantitative RT-PCR, miR-709 target validation (BORIS 3'UTR targeting) Cell cycle Low 19029807
2010 The C-terminal fragment of CTCFL predominantly consists of extended and disordered content by biophysical analysis; computational analysis predicts the N-terminal segment is also disordered, suggesting that sequence divergence in the unstructured terminal segments drives differential cofactor recruitment to distinguish CTCFL from CTCF. Biophysical characterization of recombinant C-terminal fragment (secondary structure analysis), computational disorder prediction Biochemical and biophysical research communications Low 20438700
2012 Rb2/p130 forms complexes with CTCF or BORIS under ER stress conditions in mouse medulloblastoma cells; T antigen induces chronic ER stress, associated with Caspase-12 activation and formation of Rb2/p130-CTCF or Rb2/p130-BORIS complexes as part of a non-canonical ER-dependent death pathway. Co-immunoprecipitation, western blot, cell death assays in T-Ag positive/negative medulloblastoma cell lines Cell cycle Low 22544282
2023 Boris knockout in mice reduces incidence and severity of AOM/DSS-induced colorectal cancer; Boris KO promotes γH2AX phosphorylation and DNA damage in colorectal cancer tissues, and suppresses Wnt and MAPK signaling (which mediate DNA damage repair callback). Boris KO also alleviates DSS-induced colitis via inhibition of NF-κB signaling in macrophages. Boris knockout mice, AOM/DSS colorectal cancer model, γH2AX immunofluorescence, western blot (Wnt, MAPK, NF-κB pathway), DSS-colitis model Cancer science Medium 36692143

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 BORIS, a novel male germ-line-specific protein associated with epigenetic reprogramming events, shares the same 11-zinc-finger domain with CTCF, the insulator protein involved in reading imprinting marks in the soma. Proceedings of the National Academy of Sciences of the United States of America 285 12011441
2002 The novel BORIS + CTCF gene family is uniquely involved in the epigenetics of normal biology and cancer. Seminars in cancer biology 215 12191639
2006 The testis-specific factor CTCFL cooperates with the protein methyltransferase PRMT7 in H19 imprinting control region methylation. PLoS biology 162 17048991
2005 Conditional expression of the CTCF-paralogous transcriptional factor BORIS in normal cells results in demethylation and derepression of MAGE-A1 and reactivation of other cancer-testis genes. Cancer research 162 16140943
2005 Reciprocal binding of CTCF and BORIS to the NY-ESO-1 promoter coincides with derepression of this cancer-testis gene in lung cancer cells. Cancer research 154 16140944
2007 DNA methylation-dependent regulation of BORIS/CTCFL expression in ovarian cancer. Cancer immunity 91 18095639
2019 BORIS promotes chromatin regulatory interactions in treatment-resistant cancer cells. Nature 86 31391581
2007 Expression of the CTCF-paralogous cancer-testis gene, brother of the regulator of imprinted sites (BORIS), is regulated by three alternative promoters modulated by CpG methylation and by CTCF and p53 transcription factors. Nucleic acids research 82 17962299
2015 Comparative analyses of CTCF and BORIS occupancies uncover two distinct classes of CTCF binding genomic regions. Genome biology 81 26268681
2008 BORIS, a paralogue of the transcription factor, CTCF, is aberrantly expressed in breast tumours. British journal of cancer 79 18195709
2012 The male germ cell gene regulator CTCFL is functionally different from CTCF and binds CTCF-like consensus sites in a nucleosome composition-dependent manner. Epigenetics & chromatin 74 22709888
2011 Coordinated cancer germline antigen promoter and global DNA hypomethylation in ovarian cancer: association with the BORIS/CTCF expression ratio and advanced stage. Clinical cancer research : an official journal of the American Association for Cancer Research 69 21296871
2006 Epigenetic control of CTCFL/BORIS and OCT4 expression in urogenital malignancies. Biochemical pharmacology 68 16854382
2014 Circulating cell-free cancer-testis MAGE-A RNA, BORIS RNA, let-7b and miR-202 in the blood of patients with breast cancer and benign breast diseases. British journal of cancer 66 24983365
2008 The evolution of epigenetic regulators CTCF and BORIS/CTCFL in amniotes. PLoS genetics 65 18769711
2020 CTCF and CTCFL in cancer. Current opinion in genetics & development 64 32334335
2010 Expression of a testis-specific form of Gal3st1 (CST), a gene essential for spermatogenesis, is regulated by the CTCF paralogous gene BORIS. Molecular and cellular biology 63 20231363
2017 Intragenic DNA methylation and BORIS-mediated cancer-specific splicing contribute to the Warburg effect. Proceedings of the National Academy of Sciences of the United States of America 62 29073069
2011 BORIS in human cancers -- a review. European journal of cancer (Oxford, England : 1990) 62 22019212
2007 Dynamic transcriptional regulatory complexes including BORIS, CTCF and Sp1 modulate NY-ESO-1 expression in lung cancer cells. Oncogene 62 17260018
2021 Exploring the cancer-testis antigen BORIS to design a novel multi-epitope vaccine against breast cancer based on immunoinformatics approaches. Journal of biomolecular structure & dynamics 59 33599191
2007 Global expression analysis of cancer/testis genes in uterine cancers reveals a high incidence of BORIS expression. Clinical cancer research : an official journal of the American Association for Cancer Research 59 17363524
2010 BORIS/CTCFL-mediated transcriptional regulation of the hTERT telomerase gene in testicular and ovarian tumor cells. Nucleic acids research 55 20876690
2010 The structural complexity of the human BORIS gene in gametogenesis and cancer. PloS one 52 21079786
2020 Defining the relative and combined contribution of CTCF and CTCFL to genomic regulation. Genome biology 48 32393311
2011 BORIS binding to the promoters of cancer testis antigens, MAGEA2, MAGEA3, and MAGEA4, is associated with their transcriptional activation in lung cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 47 21558405
2008 Expression of BORIS in melanoma: lack of association with MAGE-A1 activation. International journal of cancer 47 17957795
2008 DNA damage-induced upregulation of miR-709 in the germline downregulates BORIS to counteract aberrant DNA hypomethylation. Cell cycle (Georgetown, Tex.) 47 19029807
2013 CTCF and BORIS in genome regulation and cancer. Current opinion in genetics & development 46 24657531
2008 Differential expression of the embryo/cancer gene ECSA(DPPA2), the cancer/testis gene BORIS and the pluripotency structural gene OCT4, in human preimplantation development. Molecular human reproduction 45 18467432
2008 Selective apoptosis of breast cancer cells by siRNA targeting of BORIS. Biochemical and biophysical research communications 42 18355444
2021 Immunoprotective effect of an in silico designed multiepitope cancer vaccine with BORIS cancer-testis antigen target in a murine mammary carcinoma model. Scientific reports 41 34848739
2013 The cancer-testis antigen BORIS phenocopies the tumor suppressor CTCF in normal and neoplastic cells. International journal of cancer 40 23553099
2016 Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is involved in cervical cancer stemness and can be a target of immunotherapy. Oncotarget 39 26849232
2008 DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation. Cancer research 39 18413740
2008 CTCFL/BORIS is a methylation-independent DNA-binding protein that preferentially binds to the paternal H19 differentially methylated region. Cancer research 38 18632606
2006 Antitumor efficacy of DNA vaccination to the epigenetically acting tumor promoting transcription factor BORIS and CD80 molecular adjuvant. Journal of cellular biochemistry 37 16741971
2017 BORIS up-regulates OCT4 via histone methylation to promote cancer stem cell-like properties in human liver cancer cells. Cancer letters 36 28645561
2006 The potential of BORIS detected in the leukocytes of breast cancer patients as an early marker of tumorigenesis. Clinical cancer research : an official journal of the American Association for Cancer Research 36 17062669
2012 A cell cycle role for the epigenetic factor CTCF-L/BORIS. PloS one 33 22724006
2018 BORIS: a key regulator of cancer stemness. Cancer cell international 30 30323717
2014 Hypomethylation of the CTCFL/BORIS promoter and aberrant expression during endometrial cancer progression suggests a role as an Epi-driver gene. Oncotarget 30 24658009
2011 Cancer-testis antigen, BORIS based vaccine delivered by dendritic cells is extremely effective against a very aggressive and highly metastatic mouse mammary carcinoma. Cellular immunology 30 21641588
2013 Expression of the cancer-testis antigen BORIS correlates with prostate cancer. The Prostate 29 24123052
2012 Dose-dependent activation of putative oncogene SBSN by BORIS. PloS one 29 22792300
2011 Transcription factor BORIS (Brother of the Regulator of Imprinted Sites) directly induces expression of a cancer-testis antigen, TSP50, through regulated binding of BORIS to the promoter. The Journal of biological chemistry 29 21659515
2022 AMPKα2/HNF4A/BORIS/GLUT4 pathway promotes hepatocellular carcinoma cell invasion and metastasis in low glucose microenviroment. Biochemical pharmacology 28 35940258
2017 Down-regulation of BORIS/CTCFL efficiently regulates cancer stemness and metastasis in MYCN amplified neuroblastoma cell line by modulating Wnt/β-catenin signaling pathway. Biochemical and biophysical research communications 28 28104398
2016 The cancer-associated CTCFL/BORIS protein targets multiple classes of genomic repeats, with a distinct binding and functional preference for humanoid-specific SVA transposable elements. Epigenetics & chromatin 28 27588042
2011 Expression of the epigenetic factor BORIS (CTCFL) in the human genome. Journal of translational medicine 28 22168535
2013 BORIS/CTCFL mRNA isoform expression and epigenetic regulation in epithelial ovarian cancer. Cancer immunity 25 23390377
2012 Apicidin and docetaxel combination treatment drives CTCFL expression and HMGB1 release acting as potential antitumor immune response inducers in metastatic breast cancer cells. Neoplasia (New York, N.Y.) 25 23019417
2007 DNA, but not protein vaccine based on mutated BORIS antigen significantly inhibits tumor growth and prolongs the survival of mice. Gene therapy 25 17972923
2014 High expression of hTERT and stemness genes in BORIS/CTCFL positive cells isolated from embryonic cancer cells. PloS one 24 25279549
2011 CTCF and BORIS regulate Rb2/p130 gene transcription: a novel mechanism and a new paradigm for understanding the biology of lung cancer. Molecular cancer research : MCR 24 21325284
2021 The combined action of CTCF and its testis-specific paralog BORIS is essential for spermatogenesis. Nature communications 23 34158481
2017 Brother of Regulator of Imprinted Sites (BORIS) suppresses apoptosis in colorectal cancer. Scientific reports 23 28098226
2020 BORIS/CTCFL promotes a switch from a proliferative towards an invasive phenotype in melanoma cells. Cell death discovery 21 32123577
2011 Genome-wide copy number profiling using a 100K SNP array reveals novel disease-related genes BORIS and TSHZ1 in juvenile angiofibroma. International journal of oncology 21 21874228
2012 BORIS, brother of the regulator of imprinted sites, is aberrantly expressed in hepatocellular carcinoma. Genetic testing and molecular biomarkers 20 23237599
2019 BORIS Expression in Ovarian Cancer Precursor Cells Alters the CTCF Cistrome and Enhances Invasiveness through GALNT14. Molecular cancer research : MCR 19 31292201
2011 Widespread expression of BORIS/CTCFL in normal and cancer cells. PloS one 19 21811597
2010 BORIS (CTCFL) is not expressed in most human breast cell lines and high grade breast carcinomas. PloS one 18 20305816
2023 PRAME and CTCFL-reactive TCRs for the treatment of ovarian cancer. Frontiers in immunology 17 37026005
2018 Choice of binding sites for CTCFL compared to CTCF is driven by chromatin and by sequence preference. Nucleic acids research 17 29860503
2017 Brother of the regulator of the imprinted site (BORIS) variant subfamily 6 is a novel target of lung cancer stem-like cell immunotherapy. PloS one 17 28248963
2017 Discovering a binary CTCF code with a little help from BORIS. Nucleus (Austin, Tex.) 17 29077515
2019 The epigenetic factor BORIS (CTCFL) controls the androgen receptor regulatory network in ovarian cancer. Oncogenesis 16 31406110
2013 Lack of association of MTHFR rs1801133 polymorphism and CTCFL mutations with sperm methylation errors in infertile patients. Journal of assisted reproduction and genetics 16 23955684
2017 Testis-specific transcriptional regulators selectively occupy BORIS-bound CTCF target regions in mouse male germ cells. Scientific reports 15 28145452
2019 MAGEA1 inhibits the expression of BORIS via increased promoter methylation. Journal of cell science 14 30498011
2010 Susceptibility for breast cancer in young patients with short rare minisatellite alleles of BORIS. BMB reports 14 21034534
2014 Differential regulation of MAGE-A1 promoter activity by BORIS and Sp1, both interacting with the TATA binding protein. BMC cancer 13 25363021
2012 Integrating role of T antigen, Rb2/p130, CTCF and BORIS in mediating non-canonical endoplasmic reticulum-dependent death pathways triggered by chronic ER stress in mouse medulloblastoma. Cell cycle (Georgetown, Tex.) 13 22544282
2022 BTApep-TAT peptide inhibits ADP-ribosylation of BORIS to induce DNA damage in cancer. Molecular cancer 12 35918747
2010 Molecular architecture of CTCFL. Biochemical and biophysical research communications 12 20438700
2018 Molecular Lesions of Insulator CTCF and Its Paralogue CTCFL (BORIS) in Cancer: An Analysis from Published Genomic Studies. High-throughput 11 30275357
2013 BORIS/CTCFL is an RNA-binding protein that associates with polysomes. BMC cell biology 11 24279897
2012 Intronic promoter drives the BORIS-regulated expression of FerT in colon carcinoma cells. The Journal of biological chemistry 11 22223638
2022 BORIS-mediated generation of circular RNAs induces inflammation. Translational oncology 10 35182955
2024 BORIS/CTCFL epigenetically reprograms clustered CTCF binding sites into alternative transcriptional start sites. Genome biology 9 38297316
2023 Boris knockout eliminates AOM/DSS-induced in situ colorectal cancer by suppressing DNA damage repair and inflammation. Cancer science 9 36692143
2020 Hypomethylation of CTCFL promoters as a noninvasive biomarker in plasma from patients with hepatocellular carcinoma. Neoplasma 9 32386482
2020 Symbiogenesis as a driving force of evolution: The legacy of Boris Kozo-Polyansky. Bio Systems 9 33227379
2015 BORIS and CTCF are overexpressed in squamous intraepithelial lesions and cervical cancer. Genetics and molecular research : GMR 9 26125810
2015 Expression of the CTCFL Gene during Mouse Embryogenesis Causes Growth Retardation, Postnatal Lethality, and Dysregulation of the Transforming Growth Factor β Pathway. Molecular and cellular biology 9 26169830
2024 CTCF and BORIS-mediated autophagy regulation via alternative splicing of BNIP3L in breast cancer. The Journal of biological chemistry 8 38810696
2021 BORIS/CTCFL expression activates the TGFβ signaling cascade and induces Drp1 mediated mitochondrial fission in neuroblastoma. Free radical biology & medicine 8 34534628
2022 CTCFL regulates the PI3K-Akt pathway and it is a target for personalized ovarian cancer therapy. NPJ systems biology and applications 7 35132075
2021 Transcription Factor CTCFL Promotes Cell Proliferation, Migration, and Invasion in Gastric Cancer via Activating DPPA2. Computational and mathematical methods in medicine 7 34721660
2020 Early vertebrate origin of CTCFL, a CTCF paralog, revealed by proximity-guided shark genome scaffolding. Scientific reports 7 32884037
2018 The Diverging Routes of BORIS and CTCF: An Interactomic and Phylogenomic Analysis. Life (Basel, Switzerland) 7 29385718
2018 Short rare minisatellite variant of BORIS-MS2 is related to bladder cancer susceptibility. Genes & genomics 6 30499053
2017 Characteristics of the peritumoral pseudocapsule vary predictably with histologic subtype of T1 renal neoplasms. Jacob JM, Williamson SR, Gondim DD, Leese JA, Terry C, Grignon DJ, Boris RS.Urology. November 2015;86(5):956-961. Urologic oncology 6 28416107
2014 Expression analysis of BORIS during pluripotent, differentiated, cancerous, and non-cancerous cell states. Acta biochimica et biophysica Sinica 6 24928684
2011 Analysis of promoter methylation and polymorphic minisatellites of BORIS and lack of association with gastric cancer. DNA and cell biology 6 21495859
2019 The expression of transcription factor BORIS and its association with the estrogen receptor beta (ER-β) in cervical carcinogenesis. International journal of clinical and experimental pathology 5 31934165
2018 Atractyloside mimics BORIS knockdown to induce DNA damage in colorectal cancer cells. International journal of clinical and experimental pathology 5 31949703
2023 BORIS/CTCFL-mediated chromatin accessibility alterations promote a pro-invasive transcriptional signature in melanoma cells. Pigment cell & melanoma research 4 37082838
2009 No evidence for mutations of CTCFL/BORIS in Silver-Russell syndrome patients with IGF2/H19 imprinting control region 1 hypomethylation. PloS one 4 19675668

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