Affinage

EAF2

ELL-associated factor 2 · UniProt Q96CJ1

Round 2 corrected
Length
260 aa
Mass
28.8 kDa
Annotated
2026-04-28
130 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

EAF2 (ELL-associated factor 2/U19) is a transcriptional elongation cofactor and multi-organ tumor suppressor that links RNA polymerase II regulation with apoptosis, angiogenesis, and immune homeostasis. EAF2 binds ELL through an N-terminal domain (aa 68–113) that is required for nuclear speckle formation, protein stability, and pro-apoptotic activity; ELL co-expression enhances EAF2 transactivation and growth-suppressive function (PMID:12446457, PMID:17044034, PMID:16114057). Beyond transcription elongation, EAF2 directly stabilizes pVHL to suppress HIF1α-driven angiogenesis, interacts with p53 to relieve repression of the anti-angiogenic factor thrombospondin-1, and inhibits canonical Wnt/β-catenin signaling by binding β-catenin, Tcf, and c-Jun (PMID:19258512, PMID:19826414, PMID:23364330). EAF2 knockout mice develop multi-organ tumors including lung adenocarcinoma, B-cell lymphoma, and prostatic intraepithelial neoplasia, and EAF2 deficiency in germinal center B cells causes excessive humoral immunity and autoantibody production, establishing EAF2 as a critical regulator of apoptosis in both epithelial and lymphoid compartments (PMID:17873910, PMID:26935903).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2002 High

    Identifying EAF2 as a second ELL-binding partner established the molecular basis of an ELL-associated elongation cofactor family and revealed that EAF2 co-localizes with ELL in nuclear speckles.

    Evidence Co-IP across multiple cell lines, confocal microscopy, deletion mapping, and retroviral bone marrow transduction showing MLL-EAF2 fusion immortalizes progenitors

    PMID:12446457

    Open questions at the time
    • Endogenous stoichiometry of EAF2–ELL complexes undefined
    • Whether EAF2 and EAF1 compete or cooperate for ELL binding unresolved
  2. 2003 High

    Demonstrating that EAF2 overexpression induces apoptosis in diverse cell lines and that EAF2 is downregulated with allelic loss in clinical prostate cancers established it as a candidate tumor suppressor downstream of androgen signaling.

    Evidence Forced expression in 12 cell lines, in vivo xenograft apoptosis assay, LOH analysis in 23 prostate tumor specimens

    PMID:12907652

    Open questions at the time
    • Molecular pathway from EAF2 to apoptosis execution unknown at this stage
    • Whether androgen regulation of EAF2 is direct or indirect undetermined
  3. 2005 High

    Placing EAF2 downstream of non-canonical Wnt-4 signaling in Xenopus eye development and showing it regulates the eye-field transcription factor Rx linked transcription elongation factor activity to a specific developmental patterning pathway.

    Evidence Morpholino knockdown causing eye loss, mRNA rescue of Wnt-4 loss-of-function, neuralized animal cap assays in Xenopus

    PMID:15775981

    Open questions at the time
    • Direct transcriptional targets of EAF2 in eye specification besides Rx not identified
    • Whether the elongation factor activity is specifically required versus a transcription-activation function unclear
  4. 2006 Medium

    Showing that ELL binding is required for EAF2 nuclear speckle localization, protein stability, and transactivation revealed a dependency wherein EAF2 function is contingent on ELL complex formation.

    Evidence Co-transfection, co-IP, protein stability assay, and transactivation reporter assays

    PMID:16114057

    Open questions at the time
    • Whether other ELL family members (ELL2, ELL3) can substitute is unknown
    • Mechanism of ELL-mediated stabilization (proteasomal protection versus other) not determined
  5. 2007 High

    Mapping the pro-apoptotic and growth-suppressive activity to the ELL-binding domain (aa 68–113) unified the transcription elongation and tumor suppressor functions into a single structural determinant, while Eaf2-knockout mice confirmed multi-organ tumor suppressor activity in vivo.

    Evidence Deletion mutagenesis with colony formation and co-IP readouts; Eaf2-KO mice developing lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma, and PIN

    PMID:17044034 PMID:17873910

    Open questions at the time
    • Whether apoptosis requires elongation factor activity per se or an independent ELL-mediated function unresolved
    • Downstream apoptotic effectors not identified
  6. 2009 High

    Discovery that EAF2 directly binds and stabilizes pVHL, thereby suppressing HIF1α levels and angiogenesis, provided a mechanistic link between EAF2 loss and the pro-angiogenic microenvironment observed in tumors; separately, interaction with p53 to block TSP-1 repression revealed an additional anti-angiogenic axis.

    Evidence Co-IP, in vitro binding, pulse-chase stability assays, Matrigel plug angiogenesis assay in KO mice (pVHL); Co-IP with p53, TSP-1 promoter luciferase reporter, KO mouse IHC (p53/TSP-1)

    PMID:19258512 PMID:19826414

    Open questions at the time
    • Whether EAF2 binding to pVHL occurs in the same complex as ELL is unknown
    • Structural basis of EAF2–pVHL and EAF2–p53 interactions not resolved
  7. 2010 High

    ChIP-based demonstration that EAF2 directly binds the Wnt4 promoter to suppress its transcription, while Wnt4 upregulates EAF2, established a conserved auto-regulatory negative feedback loop.

    Evidence ChIP in zebrafish embryos and mammalian cells, morpholino/mRNA rescue in zebrafish, reporter assays

    PMID:20161747

    Open questions at the time
    • Whether EAF2 occupancy at the Wnt4 promoter requires ELL unresolved
    • Full set of EAF2 chromatin targets genome-wide not mapped
  8. 2013 High

    Identification of EAF2 as an inhibitor of canonical Wnt/β-catenin signaling — binding β-catenin's Armadillo repeats, Tcf, c-Jun, and Axin — expanded its role from a non-canonical Wnt effector to a direct antagonist of the canonical Wnt pathway, while genetic epistasis with Pten loss showed synergistic prostate carcinogenesis in vivo.

    Evidence Co-IP and domain mapping of β-catenin/Tcf/c-Jun/Axin complexes, β-catenin reporter assays, zebrafish epistasis; Eaf2−/−Pten+/− double-mutant mice developing spontaneous prostate cancer with elevated phospho-Akt

    PMID:23364330 PMID:23708662

    Open questions at the time
    • Whether EAF2 disrupts β-catenin–Tcf complex on chromatin or sequesters it in the nucleoplasm is unclear
    • Full spectrum of pathways synergizing with EAF2 loss beyond Pten and VHL not explored
  9. 2013 Medium

    Identification of Pirin as a binding partner that destabilizes EAF2 protein and blocks its growth-suppressive function revealed a post-translational regulatory mechanism controlling EAF2 abundance.

    Evidence Yeast two-hybrid screen validated by co-IP in mammalian cells, protein stability assays, colony formation assays

    PMID:24272884

    Open questions at the time
    • Mechanism by which Pirin destabilizes EAF2 (proteasomal, lysosomal) not determined
    • Physiological relevance of Pirin–EAF2 interaction in vivo not tested
  10. 2015 High

    Demonstrating that EAF2 binds and destabilizes FOXA1, with FOXA1 required for the enhanced AR-target gene expression seen upon EAF2 loss, placed EAF2 upstream of the FOXA1–AR transcriptional axis in prostate cells.

    Evidence Co-IP in prostate cancer cells, double-knockdown epistasis, BrdU proliferation and migration assays, cross-species validation via C. elegans RNAi screen

    PMID:25808853

    Open questions at the time
    • Whether EAF2 regulates FOXA1 at the protein stability or transcriptional level precisely is unresolved
    • Genome-wide AR-target gene changes upon EAF2 loss not profiled
  11. 2016 High

    Showing that EAF2 promotes apoptosis specifically in germinal center B cells and that its loss leads to excessive antibody production and spontaneous autoimmunity extended EAF2's tumor-suppressive apoptosis function to immune homeostasis.

    Evidence Eaf2-KO mice with enlarged GCs, elevated antibodies, collagen-induced arthritis model, spontaneous autoantibody production with aging, flow cytometry and in vitro apoptosis assays

    PMID:26935903

    Open questions at the time
    • Molecular mechanism by which EAF2 triggers GC B-cell apoptosis not identified
    • Whether EAF2's ELL-binding domain is required for B-cell apoptosis unknown
    • Relationship between EAF2-mediated B-cell lymphoma suppression and GC apoptosis not directly tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Critical open questions include the direct transcriptional target repertoire of EAF2 genome-wide, the structural basis of its interactions with ELL, pVHL, β-catenin, and p53, and the molecular effectors through which EAF2 activates apoptosis in epithelial and germinal center B cells.
  • No genome-wide chromatin occupancy map for EAF2
  • No crystal or cryo-EM structure of EAF2 or any EAF2 complex
  • Downstream apoptotic pathway (intrinsic vs extrinsic) not delineated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0098772 molecular function regulator activity 4 GO:0003677 DNA binding 1
Localization
GO:0005634 nucleus 2 GO:0005654 nucleoplasm 2
Pathway
R-HSA-74160 Gene expression (Transcription) 5 R-HSA-5357801 Programmed Cell Death 4 R-HSA-162582 Signal Transduction 3 R-HSA-1266738 Developmental Biology 2 GO:0005654 nucleoplasm 1 R-HSA-168256 Immune System 1
Partners
CTNNB1ELLFOXA1JUNPIRTCF7L2TP53VHL
Complex memberships
ELL–EAF2 transcription elongation complex

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 EAF2 (ELL-Associated Factor 2) was identified as a second ELL-binding protein, highly homologous to EAF1 (58% identity, 74% conservation). Co-immunoprecipitation from multiple cell lines confirmed the ELL–EAF2 interaction. Confocal microscopy showed endogenous EAF2 and ELL co-localize in a nuclear speckled pattern. Unlike EAF1, EAF2 binds to the amino-terminus (not the carboxy-terminus) of ELL. Both proteins contain transcriptional activation domains in a serine/aspartic acid/glutamic acid-rich region. An MLL-EAF2 fusion immortalized hematopoietic progenitors in retroviral bone marrow transduction assays. Co-immunoprecipitation, confocal microscopy, deletion mapping, retroviral bone marrow transduction Blood High 12446457
2003 During mouse embryogenesis, Eaf2 is preferentially expressed in the central nervous system, sensory and neuroendocrine organs (brain, spinal cord, ganglia, otocyst, retina, pituitary), and sites of active epithelium-mesenchymal interactions. In the developing lens, Eaf2 is absent from proliferating anterior epithelial cells but present in terminally differentiated primary lens fiber cells and non-proliferating equatorial lens fiber cells, suggesting a role in regulating cell cycle exit and lens maturation. In situ hybridization, developmental expression analysis Developmental dynamics Medium 14517999
2003 U19 (EAF2) overexpression induced apoptosis in 12 surveyed cell lines, requiring new protein synthesis. Expression of U19 in xenograft prostate tumors markedly induced apoptosis and inhibited tumor growth in vivo. U19 is an androgen/testosterone-regulated gene, and its downregulation was observed in prostate cancer cell lines and 19 of 23 clinical prostate tumor specimens, with allelic loss detected in the same specimens. Overexpression transfection, in vivo xenograft tumor model, loss of heterozygosity analysis Cancer research High 12907652
2005 In Xenopus laevis, EAF2 was identified as a transcriptional target of non-canonical (β-catenin-independent) Wnt-4 signaling, specifically expressed in the developing eye. Loss-of-function of EAF2 (morpholino knockdown) caused loss of eyes. EAF2 overexpression rescued the eye-loss phenotype caused by Wnt-4 loss-of-function. In neuralized animal caps, EAF2 regulated expression of the eye-specific transcription factor Rx, consistent with its role as an RNA polymerase II elongation factor. Morpholino knockdown, mRNA rescue, loss-of-function, in vivo Xenopus embryo assays The EMBO journal High 15775981
2006 ELL binding is required for nuclear speckle formation of U19/EAF2. Co-transfection and co-immunoprecipitation showed ELL stabilizes EAF2 protein and enhances its transactivation activity. ELL binding is thus essential for EAF2 nuclear localization, protein stability, and function as a transcription factor. Co-transfection, co-immunoprecipitation, protein stability assay, transactivation assay The Prostate Medium 16114057
2007 The region of U19/EAF2 essential for apoptosis induction and growth suppression was mapped to amino acids 68–113, which is necessary and sufficient for ELL binding. Co-expression of U19/EAF2 and ELL led to significantly increased cell death and growth suppression. Deletion mutants lacking this domain lost both ELL-binding and apoptotic activity, demonstrating that the ELL-binding domain mediates the pro-apoptotic function of EAF2. Deletion mutagenesis, co-immunoprecipitation, transfection, colony formation assay The Prostate High 17044034
2007 Homozygous or heterozygous deletion of U19/Eaf2 in mice resulted in high rates of lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma, and prostatic intraepithelial neoplasia. EAF2 deficiency enhanced cell proliferation and increased epithelial cell size in the prostate, and caused cardiac cell hypertrophy, establishing U19/Eaf2 as a tumor suppressor with a role in growth suppression and cell size control across multiple tissues. Knockout mouse model, histopathological analysis, immunohistochemistry Oncogene High 17873910
2009 U19/EAF2 co-immunoprecipitates and binds in vitro to the von Hippel-Lindau protein (pVHL). Deletion mutagenesis revealed that the N-terminus of EAF2 and both the α and β domains of pVHL are required for binding. EAF2 stabilizes pVHL, as demonstrated by protein stability and pulse-chase studies. EAF2 knockout mice and MEFs show reduced pVHL levels, and correspondingly elevated HIF1α levels and activity. EAF2-KO mice exhibit increased angiogenesis in a Matrigel plug assay, consistent with EAF2 modulating HIF1α and angiogenesis via pVHL stabilization. Co-immunoprecipitation, in vitro binding assay, deletion mutagenesis, protein stability assay, pulse-chase, KO mouse model, Matrigel plug angiogenesis assay Cancer research High 19258512
2009 U19/EAF2 co-localizes and co-immunoprecipitates with p53 in transfected cells. In a TSP-1 promoter-driven luciferase reporter assay, p53 suppressed TSP-1 promoter activity and EAF2 co-transfection blocked this p53-mediated suppression, without EAF2 alone affecting TSP-1 promoter activity. EAF2 knockout mice display reduced TSP-1 expression and increased CD31-positive blood vessels in prostate and liver, indicating EAF2 regulates thrombospondin-1 expression by blocking p53 repression of the TSP-1 promoter. Co-immunoprecipitation, luciferase reporter assay, KO mouse immunohistochemistry Oncogene Medium 19826414
2010 EAF1 and EAF2/U19 suppress Wnt4 expression by directly binding to the Wnt4 promoter, as demonstrated by chromatin immunoprecipitation (ChIP) assays in zebrafish embryos and mammalian cells. EAF1 and EAF2/U19 are in turn transcriptionally upregulated by Wnt4 (Wnt4a), establishing an auto-regulatory negative feedback loop between Wnt4 and EAF family proteins conserved between zebrafish and mammals. Disruption of this feedback loop during early zebrafish embryogenesis causes developmental defects that can be rescued by restoring appropriate Wnt4a levels. Chromatin immunoprecipitation, zebrafish morpholino/mRNA rescue, reporter assay, mammalian cell transfection PloS one High 20161747
2011 EAF2(-/-)VHL(+/-) double-mutant mice show increased incidence of proliferative hepatic vascular lesions compared to either single mutant alone, with elevated HIF1α, VEGF, and microvessel density in liver and prostate. This cooperative effect demonstrates that EAF2 and VHL act together in angiogenic regulation, and concurrent loss results in a synergistic pro-angiogenic phenotype. Double-mutant mouse model, immunohistochemistry, microvessel density quantification Angiogenesis Medium 21638067
2013 In zebrafish and mammalian cells, Eaf1 and Eaf2 inhibit canonical Wnt/β-catenin signaling and modulate mesodermal and neural patterning. By immunoprecipitation, Eaf1 and Eaf2 bind to the Armadillo repeat region and C-terminus of β-catenin, as well as to c-Jun, Tcf, and Axin, forming a novel complex. The N-terminus of Eaf1/Eaf2 binds β-catenin and acts as a dominant negative, while the C-terminus harbors a suppression domain. Both N- and C-termini must be intact for full suppressive activity. The activity is conserved across species. Morpholino/mRNA injection in zebrafish, co-immunoprecipitation, β-catenin reporter assay, deletion mapping Development (Cambridge, England) High 23364330
2013 Concomitant loss of EAF2 and one Pten allele (EAF2-/-Pten+/- mice) induced spontaneous prostate cancer in 33% of mice, demonstrating synergistic functional interaction. Prostatic tissues showed elevated phospho-Akt and phospho-p44/42, increased microvessel density, and phospho-Akt remaining high after castration. Laser-capture microdissection confirmed co-downregulation of EAF2 and Pten in >50% of high Gleason-score clinical prostate cancer specimens. Double-mutant mouse model, western blotting, immunohistochemistry, laser-capture microdissection, RT-PCR Oncogene High 23708662
2013 Pirin was identified as an EAF2/U19 binding partner by yeast two-hybrid screening. Co-immunoprecipitation confirmed interaction in mammalian cells. Overexpressed Pirin decreased EAF2/U19 protein levels in LNCaP and PC3 cells, and co-expression of Pirin blocked the growth inhibition induced by EAF2/U19 overexpression in colony formation assays, establishing Pirin as a negative regulator of EAF2 protein levels and tumor-suppressive function. Yeast two-hybrid, co-immunoprecipitation, protein stability assay, colony formation assay The Prostate Medium 24272884
2013 In EAF2(-/-) mice on C57BL/6J and FVB/NJ backgrounds, mPIN lesions were associated with reactive stroma, statistically increased prostate microvessel density, stromal inflammation preceding epithelial neoplasia, and decreased overall response to androgen deprivation after castration. EAF2 expression in human prostate cancer was negatively correlated with microvessel density. Knockout mouse model on multiple strains, immunohistochemistry, microvessel density analysis, androgen deprivation experiment PloS one Medium 24260246
2015 EAF2 co-immunoprecipitated with FOXA1 in human prostate cancer cells. EAF2 knockdown enhanced endogenous FOXA1 protein levels, while GFP-EAF2 overexpression decreased FOXA1 protein. EAF2 knockdown enhanced AR-target gene expression, cell proliferation, and migration in LNCaP cells, and FOXA1 knockdown blocked these effects, demonstrating that FOXA1 modulates EAF2's regulation of AR transcriptional activity, proliferation, and migration. The functional relationship was initially identified by RNAi screening in C. elegans eaf-1 mutants. Co-immunoprecipitation, protein stability assay, RNAi screen in C. elegans, RT-PCR, luciferase reporter, BrdU proliferation assay, transwell migration assay The Prostate High 25808853
2016 EAF2 is selectively upregulated in germinal center (GC) B cells among immune cell types. EAF2 promotes apoptosis of GC B cells both in vitro and in vivo. EAF2-deficient mice develop enlarged GCs and elevated antibody production during T-dependent immune responses. After immunization with type II collagen, EAF2-KO mice rapidly develop severe arthritis with high collagen-specific autoantibodies, and spontaneously produce anti-dsDNA, rheumatoid factor, and anti-nuclear antibodies with aging, demonstrating that EAF2-mediated GC B cell apoptosis limits excessive humoral responses and maintains self-tolerance. Knockout mouse model, flow cytometry, in vitro apoptosis assay, immunization challenge, autoantibody ELISA, arthritis scoring Nature communications High 26935903

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
2017 An Expanded View of Complex Traits: From Polygenic to Omnigenic. Cell 1888 28622505
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2006 A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nature biotechnology 1336 16964243
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2000 DNMT1 binds HDAC2 and a new co-repressor, DMAP1, to form a complex at replication foci. Nature genetics 843 10888872
2000 DNA cloning using in vitro site-specific recombination. Genome research 815 11076863
2003 Complete sequencing and characterization of 21,243 full-length human cDNAs. Nature genetics 754 14702039
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
2001 The genetic architecture of quantitative traits. Annual review of genetics 684 11700286
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2020 Physical traits of cancer. Science (New York, N.Y.) 600 33122355
2002 Finding genes that underlie complex traits. Science (New York, N.Y.) 577 12493905
2010 A Myc network accounts for similarities between embryonic stem and cancer cell transcription programs. Cell 565 20946988
2006 ING tumor suppressor proteins are critical regulators of chromatin acetylation required for genome expression and perpetuation. Molecular cell 550 16387653
2020 The Polygenic and Monogenic Basis of Blood Traits and Diseases. Cell 535 32888494
2004 Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Molecular and cellular biology 490 14966270
2013 Systems genetics approaches to understand complex traits. Nature reviews. Genetics 454 24296534
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
2022 OpenCell: Endogenous tagging for the cartography of human cellular organization. Science (New York, N.Y.) 432 35271311
2013 Origins of metastatic traits. Cancer cell 432 24135279
2015 Panorama of ancient metazoan macromolecular complexes. Nature 407 26344197
2015 Flood adaptive traits and processes: an overview. The New phytologist 406 25580769
2011 Abundant pleiotropy in human complex diseases and traits. American journal of human genetics 395 22077970
2007 Systematic analysis of the protein interaction network for the human transcription machinery reveals the identity of the 7SK capping enzyme. Molecular cell 367 17643375
2010 Posttranscriptional regulation of cancer traits by HuR. Wiley interdisciplinary reviews. RNA 352 21935886
2021 A proximity-dependent biotinylation map of a human cell. Nature 339 34079125
2004 The highly conserved and multifunctional NuA4 HAT complex. Current opinion in genetics & development 323 15196461
2000 Analysing complex genetic traits with chromosome substitution strains. Nature genetics 317 10700173
2004 Phosphoproteomic analysis of the developing mouse brain. Molecular & cellular proteomics : MCP 291 15345747
1992 Microsatellites for linkage analysis of genetic traits. Trends in genetics : TIG 284 1509520
2020 Unique and common traits in mycorrhizal symbioses. Nature reviews. Microbiology 275 32694620
2016 The cell proliferation antigen Ki-67 organises heterochromatin. eLife 265 26949251
2010 What traits are carried on mobile genetic elements, and why? Heredity 236 20332804
2005 Theoretical models of selection and mutation on quantitative traits. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 230 16048784
2009 An integrated workflow for charting the human interaction proteome: insights into the PP2A system. Molecular systems biology 223 19156129
2016 The TIP60 Complex Regulates Bivalent Chromatin Recognition by 53BP1 through Direct H4K20me Binding and H2AK15 Acetylation. Molecular cell 217 27153538
2006 Purification of a human SRCAP complex that remodels chromatin by incorporating the histone variant H2A.Z into nucleosomes. Biochemistry 212 16634648
2018 An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations. Nature communications 201 29568061
2003 Identification of new subunits of the multiprotein mammalian TRRAP/TIP60-containing histone acetyltransferase complex. The Journal of biological chemistry 193 12963728
2018 Identity Noise and Adipogenic Traits Characterize Dermal Fibroblast Aging. Cell 186 30415840
2005 The mammalian YL1 protein is a shared subunit of the TRRAP/TIP60 histone acetyltransferase and SRCAP complexes. The Journal of biological chemistry 184 15647280
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 156 30257690
2015 Strategies for fine-mapping complex traits. Human molecular genetics 156 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 144 25387784
2014 Brassinosteroid-mediated regulation of agronomic traits in rice. Plant cell reports 142 24667992
2020 Regulation of senescence traits by MAPKs. GeroScience 119 32300964
2014 Heterogeneity of dopamine neuron activity across traits and states. Neuroscience 117 25084048
2004 Detecting epistatic interactions contributing to quantitative traits. Genetic epidemiology 116 15305330
2014 Mucins suppress virulence traits of Candida albicans. mBio 111 25389175
2023 DNA methylation networks underlying mammalian traits. Science (New York, N.Y.) 93 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
2006 Engineering novel traits in plants through RNA interference. Trends in plant science 80 17030144
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
2019 Measuring phylogenetic signal between categorical traits and phylogenies. Bioinformatics (Oxford, England) 69 30358816
2017 Widespread Allelic Heterogeneity in Complex Traits. American journal of human genetics 67 28475861
2014 On the fate of sexual traits under asexuality. Biological reviews of the Cambridge Philosophical Society 67 24443922
2003 Suppression of prostate tumor growth by U19, a novel testosterone-regulated apoptosis inducer. Cancer research 67 12907652
2021 Emerging Patterns of Microbial Functional Traits. Trends in microbiology 65 34030967
2007 U19/Eaf2 knockout causes lung adenocarcinoma, B-cell lymphoma, hepatocellular carcinoma and prostatic intraepithelial neoplasia. Oncogene 59 17873910
2022 Global relationships in tree functional traits. Nature communications 55 35676261
2011 Multi-ethnic studies in complex traits. Human molecular genetics 54 21890495
2017 Comparative muscle transcriptome associated with carcass traits of Nellore cattle. BMC genomics 51 28673252
2012 Genetic and epigenetic contribution to complex traits. Human molecular genetics 51 22976472
2024 Hybrid speciation driven by multilocus introgression of ecological traits. Nature 50 38632397
2013 Eaf1 and Eaf2 negatively regulate canonical Wnt/β-catenin signaling. Development (Cambridge, England) 50 23364330
1996 Characterization of the intron-encoded U19 RNA, a new mammalian small nucleolar RNA that is not associated with fibrillarin. Molecular and cellular biology 46 8657112
2020 The ubiquitin system affects agronomic plant traits. The Journal of biological chemistry 45 32796036
2016 Genetics of Lipid and Lipoprotein Disorders and Traits. Current genetic medicine reports 44 28286704
2020 Roles of Candida albicans Mig1 and Mig2 in glucose repression, pathogenicity traits, and SNF1 essentiality. PLoS genetics 43 31961865
2023 GmJAZ3 interacts with GmRR18a and GmMYC2a to regulate seed traits in soybean. Journal of integrative plant biology 40 37066995
2014 Genetics of complex traits in psychiatry. Biological psychiatry 40 25444161
2022 Shared genetic loci between depression and cardiometabolic traits. PLoS genetics 38 35560157
2016 Genetic Consideration of Schizotypal Traits: A Review. Frontiers in psychology 37 27895608
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
2021 Global Genetic Heterogeneity in Adaptive Traits. Molecular biology and evolution 33 34240182
2023 Hyperactive nanobacteria with host-dependent traits pervade Omnitrophota. Nature microbiology 32 36928026
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
1995 Clinical traits and molecular findings in 46,XX males. Clinical genetics 29 7586641
2019 Ultrastructural traits of apoptosis. Cell biology international 27 30969020
2021 Clan genomics: From OMIM phenotypic traits to genes and biology. American journal of medical genetics. Part A 26 34405553
2021 Properties of phenotypic plasticity in discrete threshold traits. Evolution; international journal of organic evolution 26 34874068
2013 Concomitant loss of EAF2/U19 and Pten synergistically promotes prostate carcinogenesis in the mouse model. Oncogene 26 23708662
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
2023 Plasmid-Encoded Traits Vary across Environments. mBio 23 36629415
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
2023 Regulation of seed traits in soybean. aBIOTECH 20 38106437
2020 Genetic variants in MYF5 affected growth traits and beef quality traits in Chinese Qinchuan cattle. Genomics 20 32220486
2015 Genetic relationships between detailed reproductive traits and performance traits in Holstein-Friesian dairy cattle. Journal of dairy science 19 26709166
2020 Plasmids encode niche-specific traits in Lactobacillaceae. Microbial genomics 18 33166245
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
2006 ELL binding regulates U19/Eaf2 intracellular localization, stability, and transactivation. The Prostate 18 16114057
2005 Complex quality traits: now time to model. Trends in plant science 18 16216542
2023 Thermophilic Dehalococcoidia with unusual traits shed light on an unexpected past. The ISME journal 17 37041326
2022 Pregnancy outcomes among women affected with thalassemia traits. Archives of gynecology and obstetrics 17 35347380
2022 Estimation of Genetic Parameters for Conformation Traits and Milk Production Traits in Chinese Holsteins. Animals : an open access journal from MDPI 17 36611708
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
2015 Thermophilic growth and enzymatic thermostability are polyphyletic traits within Chaetomiaceae. Fungal biology 17 26615748
2008 Towards molecular breeding of reproductive traits in cereal crops. Plant biotechnology journal 17 18507792
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
2023 Variation in Sphingomonas traits across habitats and phylogenetic clades. Frontiers in microbiology 15 37138640
2021 Nanog promotes stem-like traits of glioblastoma cells. Frontiers in bioscience (Landmark edition) 15 33049683
2022 Exploring Breakthroughs in Three Traits Belonging to Seed Life. Plants (Basel, Switzerland) 14 35214823
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