Affinage

E2F6

Transcription factor E2F6 · UniProt O75461

Length
281 aa
Mass
31.8 kDa
Annotated
2026-06-09
71 papers in source corpus 33 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

E2F6 is a pRB-independent transcriptional repressor of the E2F family that lacks transactivation and pocket-protein-binding domains, heterodimerizes with DP-1/DP-2, and binds E2F recognition sites (preferring TTTCCCGC) to silence target promoters in a manner dependent on its DNA-binding and DP-heterodimerization activities (PMID:9704927, PMID:9501179, PMID:9689056). Rather than working through retinoblastoma proteins, E2F6 functions as a recruiting platform for Polycomb group machinery: it associates with RYBP, Ring1, MEL-18, mph1, and Bmi1 (PMID:11171983), forms proliferation-specific complexes with DP1/EPC1/EZH2/Sin3B (PMID:15536069), and within PRC1.6 mediates loading of the complex to a distinct subset of promoters defined by its DNA-binding specificity (PMID:29381691). Consistent with this Polycomb partnership, E2f6-null mice are viable and proliferate normally but show homeotic axial-skeleton transformations and genetically cooperate with Bmi1 in Hox repression, establishing a developmental rather than cell-cycle-essential role (PMID:12101104, PMID:18366140). During the cell cycle, E2F6 occupies G1/S (but not G2/M) target promoters specifically during S phase, where its loss permits E2F4 substitution and combined E2F4/E2F6 inhibition derepresses G1/S genes (PMID:15574595); it can also recruit the SWI/SNF ATPase BRG1 to these promoters (PMID:23082233). A major physiological function is the long-term silencing of germline and meiosis-specific genes (e.g. SMC1β, STAG3, Slc25a31) in somatic cells through H3K9/H3K27 methylation (PMID:16236716, PMID:18667754), and E2F6 is required to initiate CpG-island DNA methylation at germline genes during peri-implantation development by cooperating with MGA and directing Dnmt3b recruitment, an activity that depends on its marked-box domain (PMID:20439742, PMID:34117224). Its repressive output is dynamically regulated: Chk1 phosphorylates E2F6 during replication stress to displace it from G1/S promoters and sustain survival-promoting transcription (PMID:23954429), and E2F6 abundance is set by USP22-mediated deubiquitination and CENPU-driven proteasomal degradation (PMID:34339800, PMID:35844791), while its own promoter is activated by E2F1 in a feedback loop (PMID:16107498).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1998 High

    Established that E2F6 is a mechanistically distinct E2F member that represses without using the canonical pocket-protein route, answering how a transactivation-deficient E2F could regulate transcription.

    Evidence In vitro binding, Co-IP, reporter assays, and DNA-binding mutagenesis across three independent labs

    PMID:9501179 PMID:9689056 PMID:9704927

    Open questions at the time
    • The identity of the corepressor machinery was not yet defined
    • Endogenous physiological targets were unknown
  2. 1998 Medium

    Showed E2F6 has a cell-context-restricted function, blocking S-phase entry from quiescence but not in cycling cells, framing it as a regulator of G0 exit rather than a general cell-cycle brake.

    Evidence E2F6 overexpression with flow-cytometric cell-cycle analysis in serum-stimulated NIH 3T3 cells

    PMID:9689056

    Open questions at the time
    • Overexpression-based; endogenous requirement not tested
    • Specific target genes not identified
  3. 2001 High

    Identified E2F6's corepressor identity by linking it to Polycomb group proteins, explaining the molecular basis of its pRB-independent repression.

    Evidence Yeast two-hybrid (RYBP), endogenous reciprocal Co-IP, and domain mapping

    PMID:11171983

    Open questions at the time
    • Functional consequence of the complex at promoters not yet shown
    • Whether complex composition varies by cell state unknown
  4. 2002 High

    Defined E2F6's in vivo role through knockout mice, separating a developmental Polycomb-like function from cell-cycle control.

    Evidence Targeted E2f6 deletion in mice with skeletal analysis and MEF proliferation assays

    PMID:12101104

    Open questions at the time
    • Molecular targets driving homeotic phenotype not identified
    • Relationship to specific PcG complexes unresolved
  5. 2003 High

    Mapped genome-wide E2F6 targets and showed it acts by occluding activating E2F1, with repression not requiring H3K9 methylation at these loci.

    Evidence ChIP-chip, RNAi knockdown, and re-ChIP showing E2F1 recruitment after E2F6 loss

    PMID:12909625

    Open questions at the time
    • Mechanism of repression at H3K9-independent promoters left open
    • Did not address meiotic/germline gene targets
  6. 2004 High

    Resolved E2F6's cell-cycle-specific chromatin behavior and functional redundancy, showing S-phase-restricted occupancy of G1/S promoters with E2F4 backup.

    Evidence ChIP across synchronized cell cycle plus E2F4/E2F6 double loss-of-function derepression assays

    PMID:15574595

    Open questions at the time
    • What restricts E2F6 to G1/S vs G2/M promoters unknown
    • Recruited remodeling activity not yet defined
  7. 2004 High

    Demonstrated cell-state-specific complex assembly, defining a proliferation-specific E2F6-EPC1-EZH2-Sin3B complex.

    Evidence Yeast two-hybrid, affinity purification, and Co-IP comparing proliferating vs quiescent cells

    PMID:15536069

    Open questions at the time
    • Genome-wide targets of this specific complex not mapped
    • Functional necessity of each subunit untested
  8. 2005 High

    Identified silencing of meiosis-specific genes in somatic cells as a core E2F6 function, linking it to H3K9/H3K27 methylation.

    Evidence Knockout MEF transcriptomics, ChIP at SMC1β/STAG3 promoters, and rescue re-expression

    PMID:16236716

    Open questions at the time
    • Methyltransferase responsible not identified here
    • Whether DNA methylation is involved unaddressed
  9. 2005 Medium

    Established a feedback architecture in which E2F1 activates E2F6 expression at G1/S, providing a self-limiting circuit.

    Evidence Promoter reporter, EMSA, ChIP, and E2F1 overexpression in synchronized cells

    PMID:16107498

    Open questions at the time
    • Quantitative impact of the loop on target gene timing unknown
    • Single-lab promoter analysis
  10. 2008 Medium

    Generalized the meiotic-silencing role across most meiosis-specific genes via a conserved E2F6 element.

    Evidence Bioinformatic promoter analysis, ChIP, knockout MEF expression, and overexpression

    PMID:18667754

    Open questions at the time
    • Single-lab correlation between motif and direct binding
    • Mechanism of long-term maintenance not addressed
  11. 2008 High

    Provided in vivo genetic evidence that E2F6 and Bmi1 act in the same Polycomb pathway for Hox repression but diverge at the Ink4a-Arf locus.

    Evidence Compound E2f6/Bmi1 mutant mice with skeletal and gene-expression analysis

    PMID:18366140

    Open questions at the time
    • Molecular basis for locus-specific cooperation unknown
  12. 2010 High

    Connected E2F6 to DNA-methylation-based silencing by showing it directs Dnmt3b recruitment to germline genes in somatic tissue.

    Evidence Dnmt3b hypomorph mice, ChIP for E2F6, microarray, and bisulfite sequencing

    PMID:20439742

    Open questions at the time
    • Whether E2F6 directly contacts Dnmt3b unresolved
    • Temporal order of binding vs methylation not established
  13. 2012 Medium

    Added SWI/SNF chromatin remodeling to E2F6's repressive toolkit at G1/S promoters.

    Evidence Reciprocal Co-IP with BRG1/BAF155 and ChIP co-occupancy during S phase

    PMID:23082233

    Open questions at the time
    • Functional requirement of BRG1 for E2F6 repression not tested
    • Single-lab Co-IP/ChIP
  14. 2013 High

    Defined a stress-responsive switch, showing Chk1 phosphorylation displaces E2F6 to sustain transcription and survival during replication stress.

    Evidence In vitro kinase assay, ChIP for promoter dissociation, Chk1 knockdown, and viability/DNA-damage assays

    PMID:23954429

    Open questions at the time
    • Phosphosite mapping and phospho-mutant validation not detailed
    • Whether complex disassembly accompanies displacement unknown
  15. 2013 Medium

    Dissected the chromatin requirements for meiotic gene silencing, assigning EZH2 (PRC2) rather than Dnmt3b as the critical enzyme in development.

    Evidence ESC-to-EpiSC transition with EZH2 SET-domain and Dnmt3b deletions, ChIP, and bisulfite sequencing

    PMID:23880518

    Open questions at the time
    • Reconciliation with Dnmt3b-dependent silencing in other contexts incomplete
    • Single-lab analysis
  16. 2018 High

    Defined E2F6's role within PRC1.6 as a DNA-binding-dependent recruiter for a distinct subset of loci, in a division of labor with MGA and L3MBTL2.

    Evidence Genome-wide ChIP-seq with CRISPR ablation of individual subunits and DNA-binding-mutant rescue

    PMID:29381691

    Open questions at the time
    • What determines locus specificity between subunits unknown
    • Downstream chromatin output at E2F6-specific loci not detailed
  17. 2021 High

    Established E2F6 as the initiator of CpG-island DNA methylation at germline genes in early development, cooperating with MGA via its marked-box domain.

    Evidence E2f6 knockout mice, embryonic ChIP-seq, WGBS, domain mutagenesis, and ESC CRISPR/RNA-seq

    PMID:34117224

    Open questions at the time
    • Mechanism separating initiation from maintenance unresolved
    • Direct enzyme-recruitment contacts of the marked box not defined
  18. 2021 Medium

    Revealed post-translational control of E2F6 abundance through USP22 deubiquitination, linking it to oncogenic AKT signaling via DUSP1 repression.

    Evidence Co-IP, ubiquitination assays, ChIP at DUSP1, and knockdown epistasis in hepatocellular carcinoma cells

    PMID:34339800

    Open questions at the time
    • E3 ligase opposing USP22 not identified here
    • Generality beyond HCC untested
  19. 2022 Medium

    Identified CENPU-driven degradation of E2F6 embedded in a feedback loop with E2F1, providing a turnover mechanism that derepresses E2F1 targets.

    Evidence Co-IP, ubiquitination assays, ChIP for E2F1 at CENPU, reporter assays, and knockdown epistasis

    PMID:35844791

    Open questions at the time
    • Whether CENPU is the direct E3 ligase unresolved
    • Single-context (single-lab) finding
  20. 2022 Medium

    Documented non-canonical, context-dependent activating roles for E2F6 in cancer, recruiting KDM5C to demethylate H3K4me2 and increase SF3A3 expression.

    Evidence Co-IP, ChIP for E2F6/KDM5C co-occupancy, histone-modification ChIP, and reporter assays in bladder cancer

    PMID:35248043

    Open questions at the time
    • How E2F6 switches from repressor to activator unexplained
    • Single-lab, single-context
  21. 2016 Medium

    Showed viral hijacking of E2F6 by EBNA3C to repress E2F1, illustrating exploitation of E2F6 repression by a pathogen.

    Evidence Co-IP with domain mapping, nuclear colocalization, ChIP at E2F1 promoter, and reporter assays

    PMID:27548379

    Open questions at the time
    • Physiological relevance to viral latency not fully established
    • Single-lab
  22. 2008 Medium

    Demonstrated that DNA tumor virus oncoproteins (HPV E7, SV40 T, adenovirus E1A) inactivate E2F6 repression, broadening the theme of viral subversion.

    Evidence Co-IP, repression reporter assays, and immunofluorescence of E2F6/PcG complexes

    PMID:18579589

    Open questions at the time
    • Mechanism of complex disruption not resolved
    • Functional consequences on endogenous targets not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How E2F6's intrinsic repressive activity is switched to context-dependent transcriptional activation, and the rules governing which corepressor/coactivator complex it recruits at a given locus, remain unresolved.
  • No unifying model reconciles repressive PRC1.6/PRC2 roles with activating KDM5C/SUZ12 reports
  • Locus-specificity determinants for complex choice unknown
  • Structural basis of marked-box/repression-domain interactions undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 3 GO:0060089 molecular transducer activity 1
Localization
GO:0000228 nuclear chromosome 3 GO:0005634 nucleus 3
Pathway
R-HSA-4839726 Chromatin organization 4 R-HSA-1266738 Developmental Biology 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-1640170 Cell Cycle 2
Partners
BMI1BRG1CHK1DP1EPC1EZH2MGARYBP
Complex memberships
E2F6-DP1-EPC1-EZH2-Sin3B complexE2F6/RYBP-Ring1-MEL18-mph1-Bmi1 Polycomb complexPRC1.6

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 E2F6 lacks transactivation and retinoblastoma protein (pRB/p107/p130) binding domains, forms heterodimers with DP-1 and DP-2 proteins in vitro and in vivo, binds E2F recognition sites (preferring TTTCCCGC), and represses transcription of E2F-responsive promoters by a pRB-independent mechanism; its inhibitory effect depends on DNA binding activity and DP heterodimerization. Co-immunoprecipitation, in vitro binding assays, reporter gene assays, dominant-negative overexpression, DNA binding assays Oncogene High 9501179 9689056 9704927
1998 E2F6 overexpression in NIH 3T3 cells inhibited entry into S phase of serum-stimulated quiescent cells but had no specific effect on asynchronously cycling cells, indicating it can regulate a subset of E2F-dependent genes required for cell cycle entry from G0. Cell cycle analysis by flow cytometry, serum-stimulation of G0-arrested NIH 3T3 cells with E2F6 overexpression Proceedings of the National Academy of Sciences of the United States of America Medium 9689056
2001 E2F6 interacts with RYBP (a mammalian polycomb complex member) through the E2F6 repression domain, and endogenous E2F6 associates with polycomb group proteins RYBP, Ring1, MEL-18, mph1, and Bmi1 in a multiprotein complex. Yeast two-hybrid screen to identify RYBP; co-immunoprecipitation of endogenous proteins; domain mapping Proceedings of the National Academy of Sciences of the United States of America High 11171983
2002 E2f6 knockout mice are viable but display homeotic transformations of the axial skeleton similar to polycomb mutant mice; E2f6−/− mouse embryonic fibroblasts proliferate normally, demonstrating that E2F6 is required for developmental patterning but not normal cell cycle progression. Targeted gene deletion in mice; skeletal analysis; MEF proliferation assays EMBO reports High 12101104
2004 E2F6 associates specifically with promoters of G1/S-regulated E2F target genes during S phase but not with G2/M-regulated E2F target genes; loss of E2F6 allows E2F4 to substitute at G1/S promoters, and combined inhibition of E2F4 and E2F6 causes specific derepression of G1/S genes during S phase. Chromatin immunoprecipitation (ChIP) during synchronized cell cycle; E2F6 knockdown and E2F4/6 double inhibition with specific derepression assays Genes & development High 15574595
2004 E2F6 forms a stable core complex with DP1 and the polycomb group protein EPC1 in vitro and in vivo; this complex further associates with EZH2 and Sin3B specifically in proliferating cells (not quiescent cells), defining a novel proliferation-specific E2F6-PcG complex. Yeast two-hybrid screen; in vitro and in vivo co-immunoprecipitation; affinity purification from proliferating vs. quiescent cells The Journal of biological chemistry High 15536069
2003 E2F6 represses endogenous target promoters including BRCA1, CTIP, ART27, HP1alpha, and RBAP48 in human cells; depletion of E2F6 by RNA interference results in recruitment of E2F1 to these promoters; repression does not require histone H3 methylation at lysine 9. ChIP combined with genomic microarrays (ChIP-chip) to identify E2F6-bound promoters; RNAi knockdown; ChIP before and after knockdown The Journal of biological chemistry High 12909625
2005 E2F6 is required to silence meiosis-specific genes SMC1beta and STAG3 in somatic cells; E2F6 binds their promoters in vivo through a conserved binding site; transcriptional repression involves histone H3 methylation at both lysine 9 and lysine 27. cDNA microarray comparing wild-type and E2f6−/− MEFs; ChIP assays; re-expression rescue experiments The Journal of biological chemistry High 16236716
2005 E2F1 activating E2Fs bind the human E2F6 promoter at two functional E2F binding sites in vivo and transcriptionally upregulate E2F6 expression, establishing a regulatory feedback loop during G1/S transition. Promoter deletion/mutation reporter assays; EMSA; ChIP; E2F1 overexpression; synchronized cell cycle analysis American journal of physiology. Cell physiology Medium 16107498
2006 PHC3 (a hPRC-H polycomb complex component) associates with E2F6 and colocalizes with E2F6 in nuclear punctate bodies in differentiating/confluent (G0) cells but not in proliferating cells, suggesting a G0-specific E2F6-polycomb silencing complex. Co-immunoprecipitation; immunofluorescence colocalization in differentiating vs. proliferating cells Oncogene Medium 17001316
2008 The HPV E7 oncoprotein (low- and high-risk types), as well as SV40 T antigen and adenovirus E1A, associate with E2F6 and inactivate its transcriptional repression activity; E7-expressing cells show decreased E2F6/polycomb complex staining in a manner dependent on E2F6 association. Co-immunoprecipitation; transcriptional repression reporter assays; immunofluorescence staining of E2F6/polycomb complexes Journal of virology Medium 18579589
2008 A conserved TCCCGC E2F6-binding element is present in promoters of 79% of meiosis-specific genes; E2F6 binds in vivo to meiotic gene promoters (including Slc25a31/Ant4) and represses their expression in somatic cells; E2F6 overexpression reduces meiotic gene transcription. Bioinformatic promoter analysis; ChIP assays; E2f6 knockout MEF gene expression analysis; E2F6 overexpression Biology of reproduction Medium 18667754
2008 E2f6 and Bmi1 genetically cooperate in axial skeleton development and Hox gene repression in vivo (double mutant mice show enhanced skeletal transformations), but E2F6 does not cooperate with Bmi1 in repression of the Ink4a-Arf locus. Mouse genetic epistasis using E2f6−/− and Bmi1−/− compound mutants; skeletal analysis; gene expression Developmental dynamics High 18366140
2010 Dnmt3b is recruited to promoters of germline/meiotic genes in somatic tissues in an E2F6-dependent manner; E2F6 binding is a common feature of promoters upregulated when Dnmt3b activity is impaired; E2F6 binding is required for CpG methylation-based silencing of these genes. Dnmt3b hypomorphic mutant mice; DNA microarray; ChIP assays for E2F6 binding at target promoters; bisulfite sequencing for DNA methylation Proceedings of the National Academy of Sciences of the United States of America High 20439742
2013 Chk1 phosphorylates E2F6 in response to DNA replication stress, causing E2F6 to dissociate from G1/S target promoters; this releases repression and maintains high E2F-dependent transcription, which is required to prevent DNA damage and cell death during checkpoint activation. In vitro kinase assay (Chk1 phosphorylating E2F6); ChIP showing E2F6 dissociation from promoters after replication stress; siRNA knockdown of Chk1; cell viability and DNA damage assays Current biology : CB High 23954429
2013 E2f6-mediated repression of meiotic genes Stag3 and Smc1β during embryonic development requires EZH2 enzymatic activity (Polycomb repressive complex 2) but not Dnmt3b; EZH2 SET-domain deletion impairs repression during embryoid body differentiation. ESC-to-EpiSC transition analysis; EZH2 SET-domain deletion; Dnmt3b knockout; bisulfite sequencing; ChIP for E2f6 binding; gene expression analysis Epigenetics Medium 23880518
2012 E2F6 interacts with BRG1 (ATPase subunit of SWI/SNF chromatin-remodeling complex) and BAF155; BRG1 co-occupies G1/S gene promoters coincident with E2F6 during S phase, suggesting E2F6 recruits SWI/SNF for transcriptional repression. Co-immunoprecipitation; ChIP showing co-occupancy of BRG1 and E2F6 at G1/S promoters during S phase PloS one Medium 23082233
2018 Within the PRC1.6 complex, MGA, L3MBTL2, and E2F6 each mediate recruitment to distinct sets of genomic loci; CRISPR/Cas-mediated ablation of MGA causes complete loss of PRC1.6 binding genome-wide, while depletion of L3MBTL2 or E2F6 (but not PCGF6) causes locus-specific loss; E2F6 thus mediates PRC1.6 loading to a distinct subset of promoters. ChIP-seq genome-wide; CRISPR/Cas ablation of individual subunits; rescue experiments with DNA-binding mutants PLoS genetics High 29381691
2021 E2F6 is required to initiate (but not maintain) CpG island DNA methylation at germline genes during peri-implantation development; E2F6 cooperates with MGA to silence germline genes in ESCs through the PRC1.6 complex; the E2F6 marked box domain is critical for this function. E2f6 knockout mice; genome-wide ChIP-seq in embryonic cells; WGBS/bisulfite sequencing for DNA methylation; domain mutagenesis; CRISPR in ESCs; RNA-seq Nature communications High 34117224
2021 USP22 deubiquitinase interacts with and stabilizes E2F6 protein; USP22-mediated stabilization of E2F6 leads to transcriptional repression of phosphatase DUSP1, which in turn strengthens AKT activation in hepatocellular carcinoma cells. Co-immunoprecipitation; ubiquitination assays; ChIP showing E2F6 binding at DUSP1 promoter; siRNA knockdown epistasis; Western blot Cancer letters Medium 34339800
2022 CENPU physically interacts with E2F6 and promotes its ubiquitin-mediated proteasomal degradation; loss of E2F6 protein de-represses E2F1 transcription, and E2F1 in turn directly binds the CENPU promoter to upregulate CENPU expression, forming a positive feedback loop. Co-immunoprecipitation; ubiquitination assays; ChIP showing E2F1 binding at CENPU promoter; luciferase reporter assay; knockdown epistasis International journal of biological sciences Medium 35844791
2022 E2F6 interacts with KDM5C histone demethylase, recruits it to the SF3A3 promoter, and promotes demethylation of H3K4me2 at the CpG island, leading to increased SF3A3 expression in bladder cancer. Co-immunoprecipitation; luciferase reporter assay; ChIP for E2F6 and KDM5C co-occupancy at SF3A3 promoter; histone modification ChIP Cancer cell international Medium 35248043
2006 E2F6 represses BRCA1 transcription and negatively regulates UV-induced apoptosis; E2F6 overexpression inhibits UV-induced BRCA1 upregulation and cleavage; this effect depends on E2F6 association with the BRCA1 C-terminus in a UV-triggered manner and on E2F6 transcriptional repression of the BRCA1 promoter. Overexpression and siRNA knockdown of E2F6; ChIP at BRCA1 promoter; Co-immunoprecipitation of E2F6 with BRCA1; apoptosis assays; domain deletion mutants Cell death and differentiation Medium 17096023
2008 E2F6 represses E2F1 promoter activity directly (shown by ChIP) and competes with E2F1 for DNA binding at target sites to inhibit hypoxia-induced apoptosis; the inhibitory effects require E2F6 DNA binding activity (abrogated by E2F6.E68 DNA-binding mutant) and are independent of physical E2F6-E2F1 protein-protein association. ChIP assay for E2F6 at E2F1 promoter; reporter assays; overexpression and siRNA knockdown; E2F6 domain mutants (C-terminal deletion and DNA-binding mutant); apoptosis assays Molecular biology of the cell Medium 18562691
2022 E2F6 suppresses miR-193a expression by recruiting EZH2 to the miR-193a locus, resulting in repressive chromatin and DNA methylation at the miR-193a promoter; this E2F6-EZH2-miR-193a axis promotes ovarian cancer stemness. ChIP-PCR for E2F6 and EZH2 at miR-193a promoter; bisulfite pyrosequencing for DNA methylation; EZH2 depletion; luciferase reporter assay; cell stemness assays Cancer science Medium 30582655
2019 E2F6 expression is controlled by the EGFRvIII/AKT/NF-κB signaling pathway in glioblastoma cells, and E2F6 drives temozolomide resistance downstream of this pathway. Genome-wide CRISPR-Cas9 library screen; pathway inhibition experiments; xenograft models Advanced science Medium 31508283
2025 KDM4C histone demethylase directly binds the E2F6 promoter and epigenetically upregulates E2F6 expression in temozolomide-resistant GBM cells; pharmacological or genetic inhibition of KDM4C reduces E2F6 expression and restores TMZ sensitivity. ChIP for KDM4C at E2F6 promoter; KDM4C inhibitor (SD70); genetic knockdown; combination treatment assays Archives of pharmacal research Medium 41217736
2025 LRRFIP1 binds the E2F6 promoter and suppresses E2F6 transcription; reduced E2F6 downregulates C/EBPα to inhibit white adipocyte differentiation; re-expression of WDR77 relieves GATA3-mediated growth inhibition, placing E2F6 in the LRRFIP1/E2F6/C/EBPα regulatory axis. Luciferase reporter assay; ChIP for LRRFIP1 at E2F6 promoter; overexpression/knockdown of LRRFIP1; Western blot; adipogenic differentiation assays Diabetes & metabolism journal Low 41224206
2025 GATA3 and E2F6 directly bind the WDR77 gene promoter in vitro and in vivo and repress WDR77 promoter activity; re-expression of GATA3 and E2F6 in prostate cancer cells reduces WDR77 expression and cell growth. ChIP for E2F6 at WDR77 promoter; luciferase reporter assay; overexpression rescue experiments Transcription Low 40071854
2022 SUZ12 directly interacts with E2F6 (selectively among E2F family members) and forms a complex with EZH2; biochemical purification from HEK293 cells identified an E2F6-SUZ12-EZH2 complex; ChIP identified target genes of this complex, whose promoters are not tri-methylated at H3K27, and whose expression is paradoxically downregulated by EZH2 depletion, suggesting a non-canonical activating role. Co-immunoprecipitation; biochemical purification (Flag-SUZ12 stable cell line); ChIP; EZH2 knockdown The Kurume medical journal Low 36464274
2019 E2F6 binds to the LINC01436 promoter and represses its transcription under normoxia; in a hypoxic microenvironment, this inhibitory effect is relieved, suggesting oxygen-sensitive regulation of E2F6 transcriptional repressor activity. ChIP assay for E2F6 at LINC01436 promoter; E2F6 knockdown/overexpression with gene expression analysis under normoxia and hypoxia Molecular oncology Low 30614188
2016 EBV nuclear antigen EBNA3C physically interacts with E2F6 at both its amino and carboxy terminal domains, stabilizes E2F6 protein, and colocalizes with E2F6 in the nucleus; EBNA3C recruits E2F6 to the E2F1 promoter to repress E2F1 transcription. Co-immunoprecipitation; domain mapping; nuclear colocalization by immunofluorescence; ChIP for E2F6 at E2F1 promoter; reporter assays PLoS pathogens Medium 27548379

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 The E2F6 transcription factor is a component of the mammalian Bmi1-containing polycomb complex. Proceedings of the National Academy of Sciences of the United States of America 214 11171983
1998 E2F-6, a member of the E2F family that can behave as a transcriptional repressor. Proceedings of the National Academy of Sciences of the United States of America 192 9501179
2007 A comprehensive ChIP-chip analysis of E2F1, E2F4, and E2F6 in normal and tumor cells reveals interchangeable roles of E2F family members. Genome research 173 17908821
1998 E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription. Oncogene 164 9704927
1998 Unusual proliferation arrest and transcriptional control properties of a newly discovered E2F family member, E2F-6. Proceedings of the National Academy of Sciences of the United States of America 155 9689056
2010 Dnmt3b recruitment through E2F6 transcriptional repressor mediates germ-line gene silencing in murine somatic tissues. Proceedings of the National Academy of Sciences of the United States of America 111 20439742
2014 miR-185 suppresses tumor proliferation by directly targeting E2F6 and DNMT1 and indirectly upregulating BRCA1 in triple-negative breast cancer. Molecular cancer therapeutics 97 25319390
2008 Human papillomavirus type 16 E7 oncoprotein associates with E2F6. Journal of virology 96 18579589
2018 MGA, L3MBTL2 and E2F6 determine genomic binding of the non-canonical Polycomb repressive complex PRC1.6. PLoS genetics 94 29381691
2004 A novel repressive E2F6 complex containing the polycomb group protein, EPC1, that interacts with EZH2 in a proliferation-specific manner. The Journal of biological chemistry 93 15536069
2004 A role for E2F6 in distinguishing G1/S- and G2/M-specific transcription. Genes & development 93 15574595
2019 Genome-Wide CRISPR-Cas9 Screening Identifies NF-κB/E2F6 Responsible for EGFRvIII-Associated Temozolomide Resistance in Glioblastoma. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 75 31508283
2003 E2F6 negatively regulates BRCA1 in human cancer cells without methylation of histone H3 on lysine 9. The Journal of biological chemistry 72 12909625
2002 Homeotic transformations of the axial skeleton that accompany a targeted deletion of E2f6. EMBO reports 71 12101104
2013 Chk1 inhibits E2F6 repressor function in response to replication stress to maintain cell-cycle transcription. Current biology : CB 65 23954429
2019 Hypoxia-sensitive LINC01436 is regulated by E2F6 and acts as an oncogene by targeting miR-30a-3p in non-small cell lung cancer. Molecular oncology 45 30614188
2016 Class I HDAC inhibitor mocetinostat induces apoptosis by activation of miR-31 expression and suppression of E2F6. Cell death discovery 41 27551526
2008 A conserved E2F6-binding element in murine meiosis-specific gene promoters. Biology of reproduction 39 18667754
2006 PHC3, a component of the hPRC-H complex, associates with E2F6 during G0 and is lost in osteosarcoma tumors. Oncogene 38 17001316
2021 E2F6 initiates stable epigenetic silencing of germline genes during embryonic development. Nature communications 36 34117224
2006 E2F6 negatively regulates ultraviolet-induced apoptosis via modulation of BRCA1. Cell death and differentiation 33 17096023
2019 E2F6 functions as a competing endogenous RNA, and transcriptional repressor, to promote ovarian cancer stemness. Cancer science 32 30582655
2022 A positive feedback loop of CENPU/E2F6/E2F1 facilitates proliferation and metastasis via ubiquitination of E2F6 in hepatocellular carcinoma. International journal of biological sciences 29 35844791
2016 EBV Nuclear Antigen 3C Mediates Regulation of E2F6 to Inhibit E2F1 Transcription and Promote Cell Proliferation. PLoS pathogens 29 27548379
2005 Silencing of the meiotic genes SMC1beta and STAG3 in somatic cells by E2F6. The Journal of biological chemistry 29 16236716
2022 rtcisE2F promotes the self-renewal and metastasis of liver tumor-initiating cells via N6-methyladenosine-dependent E2F3/E2F6 mRNA stability. Science China. Life sciences 28 35266112
2008 E2F6 inhibits cobalt chloride-mimetic hypoxia-induced apoptosis through E2F1. Molecular biology of the cell 26 18562691
2017 MicroRNA-424/E2F6 feedback loop modulates cell invasion, migration and EMT in endometrial carcinoma. Oncotarget 25 29371986
2007 E2F-6 suppresses growth-associated apoptosis of human hematopoietic progenitor cells by counteracting proapoptotic activity of E2F-1. Stem cells (Dayton, Ohio) 25 17600109
2008 E2f6 and Bmi1 cooperate in axial skeletal development. Developmental dynamics : an official publication of the American Association of Anatomists 23 18366140
2005 Activating E2Fs mediate transcriptional regulation of human E2F6 repressor. American journal of physiology. Cell physiology 21 16107498
2021 Deubiquitination of the repressor E2F6 by USP22 facilitates AKT activation and tumor growth in hepatocellular carcinoma. Cancer letters 20 34339800
2022 circ_0089153 exacerbates breast cancer cells proliferation and metastasis via sponging miR-2467-3p/E2F6. Environmental toxicology 17 35225430
2022 The lncRNA CRNDE is regulated by E2F6 and sensitizes gastric cancer cells to chemotherapy by inhibiting autophagy. Journal of Cancer 17 36046639
2021 Silencing of Long Non-Coding RNA LINC00607 Prevents Tumor Proliferation of Osteosarcoma by Acting as a Sponge of miR-607 to Downregulate E2F6. Frontiers in oncology 17 33585204
2020 miR-454 suppresses the proliferation and invasion of ovarian cancer by targeting E2F6. Cancer cell international 17 32536825
2017 E2F6 Impairs Glycolysis and Activates BDH1 Expression Prior to Dilated Cardiomyopathy. PloS one 17 28085920
2020 E2F6-Mediated Downregulation of MIR22HG Facilitates the Progression of Laryngocarcinoma by Targeting the miR-5000-3p/FBXW7 Axis. Molecular and cellular biology 16 32094308
2013 E2f6-mediated repression of the meiotic Stag3 and Smc1β genes during early embryonic development requires Ezh2 and not the de novo methyltransferase Dnmt3b. Epigenetics 16 23880518
2004 Human E2F6 is alternatively spliced to generate multiple protein isoforms. Biochemical and biophysical research communications 16 15081404
2022 E2F6/KDM5C promotes SF3A3 expression and bladder cancer progression through a specific hypomethylated DNA promoter. Cancer cell international 14 35248043
2021 CircRNA DUSP16 Knockdown Suppresses Colorectal Cancer Progression by Regulating the miR-432-5p/E2F6 Axis. Cancer management and research 14 34456589
2002 Two different E2F6 proteins generated by alternative splicing and internal translation initiation. European journal of biochemistry 14 12383262
2018 MiR-425 involves in the development and progression of renal cell carcinoma by inhibiting E2F6. European review for medical and pharmacological sciences 13 30338798
2004 The NRF-1/alpha-PAL transcription factor regulates human E2F6 promoter activity. The Biochemical journal 13 15257658
2001 Molecular cloning and characterization of the mouse E2F6 gene. Biochemical and biophysical research communications 13 11594747
2022 Circ_0004676 exacerbates triple-negative breast cancer progression through regulation of the miR-377-3p/E2F6/PNO1 axis. Cell biology and toxicology 12 35870038
2021 Long noncoding RNA SLC9A3‑AS1 increases E2F6 expression by sponging microRNA‑486‑5p and thus facilitates the oncogenesis of nasopharyngeal carcinoma. Oncology reports 11 34165171
2020 CREB acts as a common transcription factor for major epigenetic repressors; DNMT3B, EZH2, CUL4B and E2F6. Medical oncology (Northwood, London, England) 11 32710193
2006 Characterisation and regulation of E2F-6 and E2F-6b in the rat heart: a potential target for myocardial regeneration? The Journal of pharmacy and pharmacology 11 16393466
2004 E2F6: a member of the E2F family that does not modulate squamous differentiation. Biochemical and biophysical research communications 11 15474455
2021 The COX10-AS1/miR-641/E2F6 Feedback Loop Is Involved in the Progression of Glioma. Frontiers in oncology 10 34381702
2017 E2F6 protein levels modulate drug induced apoptosis in cardiomyocytes. Cellular signalling 10 28964969
2012 E2F6 associates with BRG1 in transcriptional regulation. PloS one 9 23082233
2024 A hsa_circ_001726 axis regulated by E2F6 contributes to metastasis of hepatocellular carcinoma. BMC cancer 8 38166853
2008 Expression pattern of E2F6 in physical and chemical hypoxia-induced apoptosis. Sheng li xue bao : [Acta physiologica Sinica] 8 18288351
2021 Long Noncoding RNA LAMTOR5-AS1 Interference Affects MicroRNA-506-3p/E2F6-Mediated Behavior of Non-Small Cell Lung Cancer Cells. Oncology research 7 34588094
2019 E2F6 is essential for cell viability in breast cancer cells during replication stress. Turkish journal of biology = Turk biyoloji dergisi 7 31768102
2023 MicroRNA-31 regulates TNF-α and IL-17A co-induced-endothelial cell apoptosis by repressing E2F6. Biochemical and biophysical research communications 5 37178508
2023 The osteoporosis susceptibility SNP rs188303909 at 2q14.2 regulates EN1 expression by modulating DNA methylation and E2F6 binding. Journal of molecular medicine (Berlin, Germany) 5 38153509
2022 Metabolic Reprogramming of Alloreactive T Cells Through TCR/MYC/mTORC1/E2F6 Signaling in aGvHD Patients. Frontiers in immunology 4 35401560
2022 The E2F6 Transcription Factor is Associated with the Mammalian SUZ12-Containing Polycomb Complex. The Kurume medical journal 4 36464274
2019 Nuclear receptor TLX regulates islet beta cell proliferation via E2F6. Biochemical and biophysical research communications 4 30981507
2025 MiR-6837-3p protected retinal epithelial cells from oxidative stress by targeting E2F6. International ophthalmology 1 40343605
2025 Exosomal miR-98-5p Derived from Bone Marrow Mesenchymal Stem Cells Alleviates Myocardial Infarction by Regulating Autophagy via Targeting E2F6. Annals of clinical and laboratory science 1 40962448
2025 Histone demethylase KDM4C confers temozolomide resistance to glioblastoma cells by epigenetically regulating E2F6. Archives of pharmacal research 1 41217736
2024 PPP3R1 Promoter Polymorphism (Allelic Variation) Affects Tacrolimus Treatment Efficacy by Modulating E2F6 Binding Affinity. Biomedicines 1 39767802
2022 lncRNA ENST00000585827 Contributes to the Progression of Endometrial Carcinoma via Regulating miR-424/E2F6/E2F7 Axis. Applied biochemistry and biotechnology 1 36525235
2026 Elevated E2F6 Expression in Colorectal Cancer Tissues and Its Association With Clinicopathological Features. World journal of oncology 0 42136764
2025 GATA3 and E2F6 negatively regulate WDR77 expression to inhibit prostate cancer cell growth. Transcription 0 40071854
2025 LRRFIP1 Inhibits White Adipocyte Differentiation by Suppressing the E2F6/C/EBPα Axis. Diabetes & metabolism journal 0 41224206

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