Affinage

EAF2

ELL-associated factor 2 · UniProt Q96CJ1

Length
260 aa
Mass
28.8 kDa
Annotated
2026-06-09
100 papers in source corpus 20 papers cited in narrative 20 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

EAF2 is an androgen-regulated tumor suppressor that originates as a component of the ELL RNA polymerase II transcription elongation machinery, binding the amino-terminal domain of ELL through a region (residues 68–113) that also carries its growth-suppressive and apoptotic activity (PMID:12446457, PMID:17044034). ELL binding governs EAF2 nuclear speckle formation, protein stability, and transactivation, coupling the elongation partnership to EAF2 function (PMID:16114057). Its tumor-suppressive role is established in vivo: germline knockout produces multi-organ tumorigenesis including lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma, and prostatic intraepithelial neoplasia, alongside cell-size and proliferation defects (PMID:17873910), and EAF2 loss cooperates with Pten heterozygosity to drive prostate cancer through PI3K/Akt activation (PMID:23708662). EAF2 restrains angiogenesis through two convergent mechanisms: it binds and stabilizes pVHL to limit HIF-1alpha accumulation and activity (PMID:19258512, PMID:21638067), and it directly binds and selectively suppresses HIF-1alpha transactivation by disrupting p300/CBP recruitment within a hypoxia-driven negative feedback loop (PMID:24421387). EAF2 inhibits canonical Wnt/beta-catenin signaling by binding the Armadillo region and C-terminus of beta-catenin together with c-Jun, Tcf, and Axin, while participating in an autoregulatory feedback loop with noncanonical Wnt4/Wnt11/Wnt5 signaling that controls morphogenetic movements and patterning (PMID:23364330, PMID:20161747, PMID:19380582). Additional tumor-suppressive and homeostatic outputs include co-regulation of p53-dependent thrombospondin-1 expression and STAT3 activation (PMID:19826414, PMID:29518696), promotion of Ku70/Ku80-dependent nonhomologous end-joining repair (PMID:27721405), modulation of androgen receptor signaling via FOXA1 (PMID:25808853), and induction of germinal-centre B-cell apoptosis to limit autoimmunity (PMID:26935903).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2002 High

    Established EAF2's molecular identity by showing it is a dedicated partner of the ELL elongation factor with its own transcriptional activation domain, placing it in the RNA Pol II elongation machinery.

    Evidence Reciprocal Co-IP from multiple cell lines, confocal co-localization, deletion mapping, and transactivation assays

    PMID:12446457

    Open questions at the time
    • Did not establish endogenous target genes regulated by the EAF2-ELL complex
    • Physiological role beyond elongation partnership unaddressed
  2. 2003 Low

    Mapped EAF2's developmental expression to neural and sensory tissues and differentiated lens fibers, hinting at a role in cell differentiation.

    Evidence In situ hybridization across mouse embryogenesis

    PMID:14517999

    Open questions at the time
    • Expression-only data with no functional perturbation
    • No mechanism linking EAF2 to lens differentiation
  3. 2005 High

    Positioned EAF2 downstream of noncanonical Wnt-4 signaling in eye development, linking its elongation-factor activity to a developmental pathway.

    Evidence Morpholino knockdown, mRNA rescue, and in situ hybridization in Xenopus

    PMID:15775981

    Open questions at the time
    • Direct target genes of EAF2 in eye specification not defined
    • Mammalian relevance of the Wnt4-EAF2 axis not yet tested
  4. 2006 Medium

    Showed that ELL binding is not just structural but controls EAF2 localization, stability, and activity, establishing the partnership as functionally regulatory.

    Evidence Co-transfection, Co-IP, protein stability and transactivation assays in prostate cells

    PMID:16114057

    Open questions at the time
    • Mechanism of ELL-dependent stabilization (e.g., protection from degradation) not resolved
    • Single-lab data
  5. 2007 High

    Defined a minimal EAF2 region required for both ELL binding and tumor suppression, and demonstrated EAF2 is a bona fide tumor suppressor in vivo.

    Evidence Deletion mutants with colony formation/apoptosis assays; multi-organ tumor phenotyping in EAF2 knockout mice

    PMID:17044034 PMID:17873910

    Open questions at the time
    • Molecular drivers of each tissue-specific tumor type not dissected
    • Link between elongation activity and tumor suppression unresolved
  6. 2009 High

    Identified pVHL stabilization and p53/TSP-1 regulation as anti-angiogenic mechanisms, mechanistically connecting EAF2 loss to increased HIF-1alpha and vascular abnormalities.

    Evidence Co-IP, in vitro binding, pulse-chase stability, Matrigel plug assays in knockout mice; luciferase reporter and IHC for p53/TSP-1

    PMID:19258512 PMID:19826414

    Open questions at the time
    • How EAF2 stabilizes pVHL biochemically not defined
    • Relative contribution of pVHL vs p53 routes to angiogenesis unclear
  7. 2009 High

    Placed EAF family upstream of noncanonical Wnt (wnt11/wnt5) signaling controlling convergence-extension, expanding EAF2's role in morphogenesis.

    Evidence Morpholino knockdown, mRNA rescue, cell tracing, and epistasis in zebrafish

    PMID:19380582

    Open questions at the time
    • Direct transcriptional targets among wnt genes not shown in this study
    • Redundancy between EAF1 and EAF2 not separated
  8. 2010 Medium

    Demonstrated direct EAF binding to the Wnt4 promoter, establishing an autoregulatory Wnt4-EAF negative feedback loop conserved across species.

    Evidence ChIP, reporter assays, and zebrafish knockdown/rescue

    PMID:20161747

    Open questions at the time
    • Co-factors mediating promoter repression not identified
    • Single-lab data
  9. 2011 Medium

    Provided in vivo genetic evidence that EAF2 and VHL cooperate to restrain angiogenesis, and connected EAF2 to drug-response phenotypes.

    Evidence EAF2(-/-) x VHL(+/-) compound mouse cross with microvessel quantification; separate RNAi statin-response screen in HCT-116

    PMID:21483694 PMID:21638067

    Open questions at the time
    • Statin-response link is phenotype-only with no mechanism (Low confidence)
    • Tissue specificity of EAF2-VHL cooperation not explained
  10. 2013 High

    Resolved EAF2's mechanism of canonical Wnt inhibition and its synergy with PTEN loss in carcinogenesis, integrating Wnt and PI3K/Akt axes into its tumor-suppressive program.

    Evidence Co-IP, beta-catenin reporter, domain mutagenesis in zebrafish/cells; EAF2(-/-) x Pten(+/-) compound mouse model with IHC and proliferation readouts

    PMID:23364330 PMID:23708662

    Open questions at the time
    • Whether beta-catenin binding requires the ELL partnership not tested
    • C-terminal repressor identity in the beta-catenin complex unknown
  11. 2013 Medium

    Identified Pirin as a negative regulator of EAF2 stability, revealing a route by which EAF2 tumor-suppressive function can be downmodulated.

    Evidence Yeast two-hybrid screen, Co-IP, and colony formation rescue

    PMID:24272884

    Open questions at the time
    • Mechanism by which Pirin destabilizes EAF2 not defined
    • In vivo relevance not tested
  12. 2014 High

    Established a direct EAF2-HIF-1alpha negative feedback loop independent of pVHL, showing isoform-specific suppression of HIF-1alpha via blockade of p300/CBP recruitment.

    Evidence HRE reporter, Co-IP, transactivation assays in pVHL-null cells, glucose uptake and viability assays

    PMID:24421387

    Open questions at the time
    • Structural basis of HIF-1alpha vs HIF-2alpha selectivity unresolved
    • Interplay between the pVHL-dependent and pVHL-independent HIF routes not integrated
  13. 2015 Medium

    Connected EAF2 to androgen receptor signaling by showing it suppresses FOXA1, which mediates EAF2 control of AR target genes, proliferation, and migration.

    Evidence Co-IP, protein stability assays, C. elegans RNAi epistasis, and cell-based proliferation/migration assays

    PMID:25808853

    Open questions at the time
    • Mechanism of FOXA1 downregulation by EAF2 not defined
    • Single-lab data
  14. 2016 High

    Defined EAF2's DNA-repair and immune-homeostasis functions, showing it promotes Ku70/Ku80-dependent NHEJ and drives germinal-centre B-cell apoptosis to prevent autoimmunity.

    Evidence siRNA and knockout mouse models with gamma-H2ax IF, NHEJ reporter, Ku recruitment assays; immunization and collagen-induced arthritis models with flow cytometry and apoptosis assays

    PMID:26935903 PMID:27721405

    Open questions at the time
    • How EAF2 recruits/retains Ku70/Ku80 mechanistically is unresolved
    • Trigger of EAF2 upregulation in GC B cells unknown
  15. 2018 Medium

    Showed that EAF2 and p53 jointly restrain STAT3 activation, adding an oncogenic-signaling axis to EAF2's tumor-suppressive network in prostate cancer.

    Evidence RNA-seq, siRNA knockdown with STAT3 rescue, IHC in EAF2(-/-)p53(-/-) mouse prostate and human specimens

    PMID:29518696

    Open questions at the time
    • Direct mechanism linking EAF2/p53 loss to STAT3 phosphorylation not defined
    • Single-lab data

Open questions

Synthesis pass · forward-looking unresolved questions
  • How EAF2's core RNA Pol II elongation activity mechanistically unifies its diverse partner interactions (pVHL, HIF-1alpha, beta-catenin, Ku70/80, FOXA1) into a single tumor-suppressive program remains unresolved.
  • No structural model of EAF2 bound to its multiple partners
  • Whether transcriptional elongation activity is required for each non-transcriptional function untested
  • No unified picture of which interactions are direct versus complex-mediated in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 3 GO:0003677 DNA binding 1 GO:0060090 molecular adaptor activity 1 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1643685 Disease 2 R-HSA-74160 Gene expression (Transcription) 2 R-HSA-168256 Immune System 1 R-HSA-73894 DNA Repair 1 R-HSA-8953897 Cellular responses to stimuli 1
Partners
CTNNB1ELLFOXA1HIF1APIRTP53VHLXRCC6
Complex memberships
ELL elongation complexbeta-catenin/c-Jun/Tcf/Axin complex

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 EAF2 (ELL-associated factor 2) physically interacts with ELL RNA polymerase II elongation factor; endogenous EAF2 and ELL co-immunoprecipitate from multiple cell lines and co-localize in a nuclear speckled pattern by confocal microscopy. EAF2 binds to the amino-terminal domain of ELL (distinct from the carboxy-terminal domain that binds EAF1). EAF2 contains a transcriptional activation domain in its serine/aspartate/glutamate-rich region. MLL-ELL fusion protein retains the EAF1 interaction domain but not the EAF2 interaction domain. Co-immunoprecipitation from multiple cell lines, confocal microscopy, deletion mutagenesis, transcriptional activation assay, retroviral bone marrow transduction Blood High 12446457
2005 EAF2 is a downstream target gene of noncanonical (beta-catenin-independent) Wnt-4 signaling in Xenopus laevis. EAF2 is specifically expressed in the developing eye and its expression depends on Wnt-4 function. Loss-of-function of EAF2 causes loss of eyes, and EAF2 overexpression can rescue loss of Wnt-4 function. In neuralized animal caps, EAF2 regulates expression of the eye-specific transcription factor Rx, consistent with a role as an RNA polymerase II elongation factor. Morpholino knockdown, mRNA rescue injections, in situ hybridization, Xenopus laevis loss-of-function assays The EMBO journal High 15775981
2006 ELL binding is required for nuclear speckle formation of EAF2, stabilizes EAF2 protein, and enhances its transactivation activity. ELL binding therefore controls EAF2 intracellular localization, stability, and transcriptional function. Co-transfection, co-immunoprecipitation, protein stability assay, transactivation assay The Prostate Medium 16114057
2007 The region of EAF2 (amino acids 68–113) is necessary and sufficient for both ELL binding and for induction of apoptosis and growth suppression in prostate cancer cells. Co-expression of EAF2 and ELL leads to significantly increased cell death and growth suppression, indicating that ELL interaction is essential for EAF2's apoptotic and tumor-suppressive functions. Transfection of deletion mutants, colony formation assay, co-immunoprecipitation The Prostate Medium 17044034
2007 Homozygous or heterozygous knockout of EAF2 in mice results in high rates of lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma, and prostatic intraepithelial neoplasia. EAF2 deficiency in the mouse prostate enhances cell proliferation and increases epithelial cell size, and the knockout mice also exhibit cardiac cell hypertrophy, establishing EAF2 as a tumor suppressor with roles in growth suppression and cell size control in multiple tissues. Murine knockout model (homozygous and heterozygous), histopathology, cell proliferation analysis Oncogene High 17873910
2009 EAF2 physically binds to pVHL (von Hippel-Lindau protein) via its NH2-terminus (EAF2) and both alpha and beta domains of pVHL. EAF2 stabilizes pVHL protein as shown by stability and pulse-chase studies. EAF2 knockout mice show reduced pVHL levels in testes and MEFs and exhibit increased HIF-1alpha levels and activity, increased angiogenesis in Matrigel plug assays, and vascular system abnormalities consistent with a pVHL-dependent mechanism. Co-immunoprecipitation, in vitro binding assay, deletion mutagenesis, protein stability assay, pulse-chase study, Matrigel plug assay, EAF2 knockout mouse model Cancer research High 19258512
2009 EAF2 co-localizes and co-immunoprecipitates with p53 in transfected cells. In a TSP-1 promoter luciferase reporter assay, p53 suppresses TSP-1 promoter activity, and co-transfection with EAF2 blocks this p53-mediated suppression. EAF2 knockout mice show downregulation of the anti-angiogenic protein thrombospondin-1 (TSP-1) in prostate and liver, and increased CD31-positive blood vessels in liver, suggesting EAF2 regulates TSP-1 expression by blocking p53 repression of the TSP-1 promoter. Co-immunoprecipitation, luciferase reporter assay, immunohistochemistry, EAF2 knockout mouse model Oncogene Medium 19826414
2009 EAF1 and EAF2 (Eafs) maintain expression levels of wnt11 and wnt5 in zebrafish, acting upstream of noncanonical Wnt signaling to mediate convergence and extension movements and midline convergence of organ precursors. Eaf morpholino knockdown disrupts cell migration (shown by kaeda mRNA cell tracing) and wnt11/wnt5 mRNA rescue recovers convergence and extension defects. rhoA mRNA rescue is more effective than either wnt alone, consistent with Wnt11/Wnt5 converging on RhoA. Morpholino knockdown, mRNA rescue, in situ hybridization, kaeda mRNA cell tracing, genetic epistasis analysis in zebrafish The Journal of biological chemistry High 19380582
2010 EAF1 and EAF2 are upregulated by Wnt4 signaling, and both proteins directly bind the Wnt4 promoter (shown by chromatin immunoprecipitation) to suppress Wnt4 expression, establishing an auto-regulatory negative feedback loop between Wnt4 and the EAF family conserved between zebrafish and mammals. Chromatin immunoprecipitation, reporter assay, morpholino knockdown and mRNA rescue in zebrafish, RT-PCR PloS one Medium 20161747
2011 Combined loss of EAF2 and VHL heterozygosity cooperatively increases angiogenesis in mouse liver and prostate, with increased microvessel density and HIF-1alpha/VEGF staining. EAF2(-/-) VHL(+/-) mice show higher incidence of proliferative hepatic vascular lesions and prostatic intraepithelial neoplasia compared to either single mutant, demonstrating in vivo cooperation between EAF2 and VHL in angiogenic regulation. Mouse genetic cross (EAF2(-/-) x VHL(+/-)), immunohistochemistry, microvessel density quantification Angiogenesis Medium 21638067
2013 EAF1 and EAF2 inhibit canonical Wnt/beta-catenin signaling in zebrafish and cultured cells. By immunoprecipitation, Eaf1 and Eaf2 bind to the Armadillo repeat region and C-terminus of beta-catenin, and also interact with c-Jun, Tcf, and Axin, forming a novel complex. The N-terminus of Eaf1/Eaf2 binds beta-catenin and exhibits dominant-negative activity; the C-terminus contains a suppression domain or recruits a repressor. Both termini must be intact for full suppressive activity. Loss- and gain-of-function assays in zebrafish confirm modulation of mesodermal and neural patterning. Morpholino knockdown, mRNA injection, immunoprecipitation, beta-catenin reporter assay, deletion mutagenesis in zebrafish and cultured cells Development (Cambridge, England) High 23364330
2013 Concomitant loss of EAF2 and heterozygous loss of Pten synergistically promotes prostate cancer in mice (33% incidence), with elevated phospho-Akt, phospho-p44/42, increased microvessel density, and higher epithelial proliferation in intact and castrated EAF2(-/-)Pten(+/-) mice compared to single mutants. This demonstrates functional interaction between EAF2 and the PTEN/PI3K/Akt pathway in prostate carcinogenesis. Compound knockout mouse model (EAF2(-/-) x Pten(+/-)), immunohistochemistry, laser-capture microdissection with RT-PCR, proliferation analysis Oncogene High 23708662
2013 Pirin was identified as a binding partner of EAF2 by yeast two-hybrid screening and confirmed by co-immunoprecipitation in mammalian cells. Overexpressed Pirin decreases EAF2 protein levels in prostate cancer cell lines and blocks EAF2-mediated growth inhibition of LNCaP cells, establishing Pirin as a regulator of EAF2 protein stability and function. Yeast two-hybrid screening, co-immunoprecipitation, colony formation assay The Prostate Medium 24272884
2014 EAF2 is a hypoxia-response gene containing a hypoxia response element (HRE) in its promoter. HIF-1alpha (but not HIF-2alpha) induces EAF2 expression under hypoxia. EAF2 in turn binds and suppresses HIF-1alpha (but not HIF-2alpha) transactivation by disrupting p300/CBP recruitment to HIF-1alpha, independently of FIH-1 and Sirt1. EAF2 also protects cells against hypoxia-induced cell death and inhibits cellular glucose uptake under hypoxia, establishing a negative feedback loop between EAF2 and HIF-1alpha. HRE reporter assay, co-immunoprecipitation, luciferase transactivation assay, pVHL-null cell lines (RCC4 and 786-O), glucose uptake assay, cell viability assay Molecular and cellular biology High 24421387
2015 EAF2 co-immunoprecipitates with FOXA1 in human prostate cancer cells. EAF2 knockdown enhances endogenous FOXA1 protein levels, while GFP-EAF2 overexpression down-regulates FOXA1 protein. FOXA1 knockdown inhibits EAF2-knockdown-induced enhancement of AR target gene expression, cell proliferation, and migration in LNCaP cells, indicating that FOXA1 mediates EAF2 regulation of AR signaling, proliferation, and migration. The ortholog pha-4 (C. elegans FOXA1) was identified by RNAi screen in eaf-1 mutant worms as synergistically enhancing reduced fertility. Co-immunoprecipitation, protein stability assay, RNAi screen in C. elegans, RT-PCR, luciferase reporter assay, BrdU proliferation assay, transwell migration assay The Prostate Medium 25808853
2016 EAF2 is selectively upregulated in germinal centre (GC) B cells and promotes their apoptosis both in vitro and in vivo. EAF2 deficiency results in enlarged GCs and elevated antibody production during T-dependent immune responses. EAF2-knockout mice develop severe collagen-induced arthritis with high autoantibody titers and spontaneously produce anti-dsDNA, rheumatoid factor, and anti-nuclear antibodies with age, demonstrating that EAF2-mediated apoptosis in GC B cells limits excessive humoral immune responses and maintains self-tolerance. EAF2 knockout mouse model, immunization assay, collagen-induced arthritis model, flow cytometry, apoptosis assay in vitro and in vivo Nature communications High 26935903
2016 EAF2 and EAF1 are required for the recruitment and retention of Ku70/Ku80 to DNA damage sites and play a functional role in nonhomologous end-joining (NHEJ) DNA repair. EAF2 knockdown sensitizes prostate cancer cells to DNA damage in a p53-independent manner, and EAF2 knockout mouse prostate is sensitized to gamma-irradiation. EAF2 knockdown blocks androgen-mediated repression of gamma-H2ax induction by doxorubicin, suggesting EAF2 mediates androgen protection against DNA damage via Ku70/Ku80. siRNA knockdown, EAF2 knockout mouse model, gamma-H2ax immunofluorescence, DNA damage sensitivity assay (doxorubicin, gamma-irradiation), NHEJ reporter assay, Ku70/Ku80 recruitment assay at DNA damage sites Oncogene High 27721405
2018 Concurrent knockdown of EAF2 and p53 in prostate cancer cells activates STAT3 signaling (increased p-STAT3), and STAT3 knockdown abrogates the stimulation of cell proliferation caused by co-knockdown of EAF2 and p53. EAF2(-/-)p53(-/-) mouse prostate shows significantly increased p-STAT3 immunostaining, establishing that EAF2 and p53 co-regulate STAT3 activation in prostate cancer. RNA-seq, siRNA knockdown, immunohistochemistry in mouse prostate (Eaf2-/-p53-/- model), human prostate cancer specimen immunostaining, cell proliferation assay Neoplasia (New York, N.Y.) Medium 29518696
2003 Murine Eaf2 is preferentially expressed in the central nervous system, sensory and neuroendocrine organs during embryogenesis. In the developing lens, Eaf2 is absent from proliferating anterior lens epithelial cells but present in terminally differentiated primary lens fiber cells and non-proliferating lens fiber cells in the equatorial zone, suggesting a role in regulating lens cell differentiation and maturation. In situ hybridization during mouse embryogenesis, spatial expression analysis Developmental dynamics Low 14517999
2011 RNAi-mediated silencing of EAF2 in HCT-116 colon cancer cells modulates cellular response to both simvastatin and lovastatin, as validated by functional RNAi experiments following bioinformatic identification of EAF2 from NCI60 panel data. Bioinformatic analysis of NCI60 SNP data, RNAi functional validation in HCT-116 cells PloS one Low 21483694

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 An Expanded View of Complex Traits: From Polygenic to Omnigenic. Cell 1927 28622505
2001 The genetic architecture of quantitative traits. Annual review of genetics 685 11700286
2020 Physical traits of cancer. Science (New York, N.Y.) 624 33122355
2002 Finding genes that underlie complex traits. Science (New York, N.Y.) 578 12493905
2020 The Polygenic and Monogenic Basis of Blood Traits and Diseases. Cell 552 32888494
2013 Systems genetics approaches to understand complex traits. Nature reviews. Genetics 458 24296534
2013 Origins of metastatic traits. Cancer cell 436 24135279
2015 Flood adaptive traits and processes: an overview. The New phytologist 413 25580769
2011 Abundant pleiotropy in human complex diseases and traits. American journal of human genetics 399 22077970
2010 Posttranscriptional regulation of cancer traits by HuR. Wiley interdisciplinary reviews. RNA 352 21935886
2000 Analysing complex genetic traits with chromosome substitution strains. Nature genetics 318 10700173
2020 Unique and common traits in mycorrhizal symbioses. Nature reviews. Microbiology 284 32694620
2015 Fungal traits that drive ecosystem dynamics on land. Microbiology and molecular biology reviews : MMBR 260 25971588
2010 What traits are carried on mobile genetic elements, and why? Heredity 238 20332804
2005 Theoretical models of selection and mutation on quantitative traits. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 233 16048784
2018 Identity Noise and Adipogenic Traits Characterize Dermal Fibroblast Aging. Cell 188 30415840
2004 Regulatory polymorphisms underlying complex disease traits. Journal of molecular medicine (Berlin, Germany) 167 15592805
2018 Epigenetic prediction of complex traits and death. Genome biology 160 30257690
2015 Strategies for fine-mapping complex traits. Human molecular genetics 157 26157023
2014 Invited review: overview of new traits and phenotyping strategies in dairy cattle with a focus on functional traits. Animal : an international journal of animal bioscience 148 25387784
2014 Brassinosteroid-mediated regulation of agronomic traits in rice. Plant cell reports 144 24667992
2013 Autism traits in the RASopathies. Journal of medical genetics 136 24101678
2020 Regulation of senescence traits by MAPKs. GeroScience 123 32300964
2015 Predicting microbial traits with phylogenies. The ISME journal 121 26371406
2014 Heterogeneity of dopamine neuron activity across traits and states. Neuroscience 117 25084048
1999 Clines in polygenic traits. Genetical research 116 10689800
2014 Mucins suppress virulence traits of Candida albicans. mBio 112 25389175
2023 DNA methylation networks underlying mammalian traits. Science (New York, N.Y.) 97 37561875
2005 Noncanonical Wnt-4 signaling and EAF2 are required for eye development in Xenopus laevis. The EMBO journal 83 15775981
2017 LGR5 promotes cancer stem cell traits and chemoresistance in cervical cancer. Cell death & disease 80 28880275
1999 Properties of spontaneous mutations affecting quantitative traits. Genetical research 79 10689810
2005 Evolution of selenium utilization traits. Genome biology 72 16086848
2002 ELL-associated factor 2 (EAF2), a functional homolog of EAF1 with alternative ELL binding properties. Blood 72 12446457
2014 On the fate of sexual traits under asexuality. Biological reviews of the Cambridge Philosophical Society 71 24443922
2021 Emerging Patterns of Microbial Functional Traits. Trends in microbiology 68 34030967
2017 Widespread Allelic Heterogeneity in Complex Traits. American journal of human genetics 67 28475861
2022 Global relationships in tree functional traits. Nature communications 59 35676261
2007 U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia. Oncogene 59 17873910
2024 Hybrid speciation driven by multilocus introgression of ecological traits. Nature 55 38632397
2012 Genetic and epigenetic contribution to complex traits. Human molecular genetics 51 22976472
2013 Eaf1 and Eaf2 negatively regulate canonical Wnt/β-catenin signaling. Development (Cambridge, England) 50 23364330
2020 The ubiquitin system affects agronomic plant traits. The Journal of biological chemistry 46 32796036
2016 Genetics of Lipid and Lipoprotein Disorders and Traits. Current genetic medicine reports 45 28286704
2020 Roles of Candida albicans Mig1 and Mig2 in glucose repression, pathogenicity traits, and SNF1 essentiality. PLoS genetics 44 31961865
2009 Zebrafish eaf1 and eaf2/u19 mediate effective convergence and extension movements through the maintenance of wnt11 and wnt5 expression. The Journal of biological chemistry 44 19380582
2015 Mapping complex traits as a dynamic system. Physics of life reviews 43 25772476
2023 GmJAZ3 interacts with GmRR18a and GmMYC2a to regulate seed traits in soybean. Journal of integrative plant biology 41 37066995
2022 Shared genetic loci between depression and cardiometabolic traits. PLoS genetics 41 35560157
2020 Fungal Traits Important for Soil Aggregation. Frontiers in microbiology 40 31998249
2014 Genetics of complex traits in psychiatry. Biological psychiatry 40 25444161
2016 Genetic Consideration of Schizotypal Traits: A Review. Frontiers in psychology 37 27895608
2014 EAF2 suppresses hypoxia-induced factor 1α transcriptional activity by disrupting its interaction with coactivator CBP/p300. Molecular and cellular biology 37 24421387
2009 Tumor suppressor U19/EAF2 regulates thrombospondin-1 expression via p53. Oncogene 36 19826414
2011 The unexpected traits associated with core promoter elements. Transcription 35 22231114
2023 Hyperactive nanobacteria with host-dependent traits pervade Omnitrophota. Nature microbiology 33 36928026
2021 Global Genetic Heterogeneity in Adaptive Traits. Molecular biology and evolution 33 34240182
2022 Runs of Homozygosity Revealed Reproductive Traits of Hu Sheep. Genes 32 36292733
2021 Metabolomics Intervention Towards Better Understanding of Plant Traits. Cells 31 33562333
2016 EAF2 mediates germinal centre B-cell apoptosis to suppress excessive immune responses and prevent autoimmunity. Nature communications 31 26935903
2004 Evolution of developmental traits. Current opinion in plant biology 31 14732447
2009 U19/Eaf2 binds to and stabilizes von hippel-lindau protein. Cancer research 30 19258512
2017 New traits in crops produced by genome editing techniques based on deletions. Plant biotechnology reports 28 28386301
2023 Plasmid-Encoded Traits Vary across Environments. mBio 27 36629415
2021 Properties of phenotypic plasticity in discrete threshold traits. Evolution; international journal of organic evolution 27 34874068
2019 Ultrastructural traits of apoptosis. Cell biology international 27 30969020
2009 Relationships between reproductive traits of heifers and cows and yield traits for Holsteins in Japan. Journal of dairy science 27 19620689
2013 Modulation of cancer traits by tumor suppressor microRNAs. International journal of molecular sciences 26 23325049
2013 Concomitant loss of EAF2/U19 and Pten synergistically promotes prostate carcinogenesis in the mouse model. Oncogene 26 23708662
2020 Metabolic Traits in Cutaneous Melanoma. Frontiers in oncology 25 32509589
2019 Plant Networks as Traits and Hypotheses: Moving Beyond Description. Trends in plant science 25 31300195
2015 FOXA1 modulates EAF2 regulation of AR transcriptional activity, cell proliferation, and migration in prostate cancer cells. The Prostate 25 25808853
2021 Association of structural variation with cardiometabolic traits in Finns. American journal of human genetics 24 33798444
2021 Expression of ovine CTNNA3 and CAP2 genes and their association with growth traits. Gene 24 34481004
2016 EAF2 regulates DNA repair through Ku70/Ku80 in the prostate. Oncogene 24 27721405
2023 Regulation of seed traits in soybean. aBIOTECH 23 38106437
2014 SLC6A4 polymorphism, population genetics, and psychiatric traits. Human genetics 22 24385047
2011 EAF2 loss enhances angiogenic effects of Von Hippel-Lindau heterozygosity on the murine liver and prostate. Angiogenesis 22 21638067
1984 Traits for sire selection related to udder health and management. Journal of dairy science 22 6371078
2021 Improving architectural traits of maize inflorescences. Molecular breeding : new strategies in plant improvement 21 37309422
2015 Epistasis for quantitative traits in Drosophila. Methods in molecular biology (Clifton, N.J.) 21 25403527
2003 Expression of murine ELL-associated factor 2 (Eaf2) is developmentally regulated. Developmental dynamics : an official publication of the American Association of Anatomists 21 14517999
2020 Genetic variants in MYF5 affected growth traits and beef quality traits in Chinese Qinchuan cattle. Genomics 20 32220486
2018 EAF2 and p53 Co-Regulate STAT3 Activation in Prostate Cancer. Neoplasia (New York, N.Y.) 20 29518696
2022 Pregnancy outcomes among women affected with thalassemia traits. Archives of gynecology and obstetrics 19 35347380
2022 Estimation of Genetic Parameters for Conformation Traits and Milk Production Traits in Chinese Holsteins. Animals : an open access journal from MDPI 18 36611708
2012 Genomics of complex traits. Annals of the New York Academy of Sciences 18 23050961
2010 Negative feedback regulation of Wnt4 signaling by EAF1 and EAF2/U19. PloS one 18 20161747
2008 Towards molecular breeding of reproductive traits in cereal crops. Plant biotechnology journal 18 18507792
2006 ELL binding regulates U19/Eaf2 intracellular localization, stability, and transactivation. The Prostate 18 16114057
2023 Thermophilic Dehalococcoidia with unusual traits shed light on an unexpected past. The ISME journal 17 37041326
2023 Variation in Sphingomonas traits across habitats and phylogenetic clades. Frontiers in microbiology 17 37138640
2019 Expression of Behavioural Traits in Goldendoodles and Labradoodles. Animals : an open access journal from MDPI 17 31861203
2017 Epigenetic regulation of agronomical traits in Brassicaceae. Plant cell reports 17 29058037
2013 Pirin down-regulates the EAF2/U19 protein and alleviates its growth inhibition in prostate cancer cells. The Prostate 16 24272884
2011 Male reproductive traits and their relationship to reproductive traits in their female progeny: a systematic review. Reproduction in domestic animals = Zuchthygiene 16 21332828
2022 Exploring Breakthroughs in Three Traits Belonging to Seed Life. Plants (Basel, Switzerland) 15 35214823
2021 Nanog promotes stem-like traits of glioblastoma cells. Frontiers in bioscience (Landmark edition) 15 33049683
2011 NCI60 cancer cell line panel data and RNAi analysis help identify EAF2 as a modulator of simvastatin and lovastatin response in HCT-116 cells. PloS one 15 21483694
2022 Epigenetics and its role in effecting agronomical traits. Frontiers in plant science 14 36046583
2007 Apoptosis induction and growth suppression by U19/Eaf2 is mediated through its ELL-binding domain. The Prostate 14 17044034

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