Affinage

RUNX1

Runt-related transcription factor 1 · UniProt Q01196

Length
453 aa
Mass
48.7 kDa
Annotated
2026-06-10
100 papers in source corpus 35 papers cited in narrative 35 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RUNX1 is the DNA-binding subunit of core-binding factor and a master transcriptional regulator of definitive hematopoiesis, essential for the formation of intra-aortic hematopoietic clusters from hemogenic endothelium in the AGM region and for the establishment of all definitive blood progenitors (PMID:8622955, PMID:10226014). It functions as a context-dependent transcription factor, binding RUNX motifs at promoters and enhancers and cooperating combinatorially with lineage partners: it physically interacts with GATA-1 to drive megakaryocytic gene programs (PMID:12576332), displaces the autoinhibitory module of Ets1 to license Ets1 activation (a mechanism resolved by ternary crystal structure) (PMID:24646888), cooperates with EBF1 in B-cell specification (PMID:20385820), and excludes corepressors (Eto2, Sin3A, Hdac2) from PU.1 complexes to permit myeloid differentiation (PMID:21518930). Genome-wide, RUNX1 co-occupies p300-marked enhancers enriched for RUNX, ETS, and GATA motifs to control megakaryocyte maturation (PMID:23717578), and is guided to target loci by the lncRNA LOUP, which loops the PU.1 enhancer to its promoter (PMID:33971010). Beyond blood, RUNX1 drives mesenchymal commitment to chondrogenesis through induction of Sox5/Sox6 with RUNX2 (PMID:16059634, PMID:20181744), prevents fibrotic conversion of the bone marrow HSC niche in CAR cells (PMID:35551452), and promotes myofibroblast differentiation and lung fibrosis downstream of TGF-β (PMID:35048404). RUNX1 abundance and activity are tightly controlled: Cdk1/2-mediated phosphorylation of S276/S303 targets it for APC/Cdc20 degradation (PMID:17015473), STUB1 ubiquitinates it and promotes nuclear export (PMID:28536267), PRMT1 arginine methylation blocks corepressor binding (PMID:26010396), and upstream signals including Notch1 (PMID:16888092), FLT3-ITD (PMID:28213513), CDK6 (PMID:29523786), and cohesin/CTCF (PMID:24321385) modulate its expression. Haploinsufficiency from germline RUNX1 mutations causes familial platelet disorder with predisposition to AML, and Runt-domain dosage directly controls megakaryopoiesis and platelet signaling (PMID:10508512, PMID:14525764); dominant-negative variants produce T-ALL (PMID:34166225). In leukemic fusions (RUNX1-ETO, RUNX1-EVI1), the RUNX1 DNA-binding domain requires CBFβ heterodimerization for transformation (PMID:19179469, PMID:28360416), while the fusion partner dictates the genome-wide binding landscape and transcription factor dependencies (PMID:28538183, PMID:33382982).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 High

    Established that RUNX1 is genetically required for definitive but not primitive hematopoiesis, defining its core developmental role.

    Evidence Germline Cbfa2-null mouse with embryological analysis of hematopoietic progenitors

    PMID:8622955

    Open questions at the time
    • Did not resolve the cellular origin of the blocked progenitors
    • Did not identify direct transcriptional targets
  2. 1999 High

    Localized RUNX1's essential function to the endothelial-to-hematopoietic transition, showing it specifies blood from hemogenic endothelium in the AGM.

    Evidence Cbfa2-null analysis with in situ expression mapping and endothelial lineage studies

    PMID:10226014

    Open questions at the time
    • Molecular trigger of cluster emergence not defined
    • Did not identify co-regulators in hemogenic endothelium
  3. 1999 High

    Linked RUNX1 dosage directly to human disease, demonstrating that Runt-domain haploinsufficiency causes familial platelet disorder with AML predisposition.

    Evidence Mutational analysis of FPD/AML pedigrees with megakaryocyte colony assays

    PMID:10508512

    Open questions at the time
    • Mechanism of leukemic progression from haploinsufficiency unresolved
    • Specific megakaryocytic target genes not enumerated
  4. 2003 Medium

    Defined how RUNX1 builds the megakaryocytic program through physical cooperation with GATA-1 and how RUNX1-ETO subverts it.

    Evidence Co-IP, reporter cotransfection, and retroviral overexpression in K562 cells

    PMID:12576332 PMID:14525764

    Open questions at the time
    • Interaction surface not structurally mapped
    • Single-lab reporter-based functional data
  5. 2006 High

    Revealed two layers of regulation: Cdk-driven phosphodegron control of RUNX1 stability and RUNX1's role in excluding corepressors from PU.1 to enable myeloid differentiation.

    Evidence In vitro kinase/stability assays with phospho-mutants; reciprocal Co-IP, ChIP and knockdown in macrophage model

    PMID:17015473 PMID:21518930

    Open questions at the time
    • In vivo relevance of S276/S303 degradation not tested in animals
    • How full-length RUNX1 physically excludes corepressors not structurally defined
  6. 2006 Medium

    Placed RUNX1 downstream of Notch1 in definitive hematopoiesis and showed it commits mesenchyme to early chondrogenesis, broadening its developmental scope.

    Evidence Notch1-null rescue by retroviral Runx1; gain/loss-of-function in limb-bud micromass cultures

    PMID:16059634 PMID:16888092

    Open questions at the time
    • Direct chondrogenic target genes not yet identified at this stage
    • Notch-to-Runx1 regulation not shown to be direct
  7. 2010 High

    Demonstrated combinatorial partnerships of RUNX1 in distinct lineages: cooperation with RUNX2 to drive Sox5/Sox6 in sternal chondrogenesis and with EBF1 in B-cell specification.

    Evidence Conditional and compound-heterozygous knockout mice with expression and co-expression assays

    PMID:20181744 PMID:20385820

    Open questions at the time
    • Direct binding to Sox5/Sox6 and B-cell targets only partially mapped
    • Whether RUNX1/RUNX2 and RUNX1/EBF1 form physical complexes not resolved
  8. 2013 High

    Mapped RUNX1's genome-wide enhancer occupancy in megakaryocytes and showed cohesin/CTCF set RUNX1 expression levels through its promoters and cis-elements.

    Evidence Megakaryocyte-specific conditional KO with Runx1/p300 ChIP-seq and in vivo enhancer transgenesis; ChIP and depletion of cohesin/CTCF

    PMID:23717578 PMID:24321385

    Open questions at the time
    • How RUNX1 selects p300-bound enhancers versus repressive sites unclear
    • 3D chromatin consequences of cohesin/CTCF at RUNX1 not fully resolved
  9. 2014 High

    Provided the structural basis for RUNX1-mediated transactivation, showing it displaces the Ets1 autoinhibitory module to relieve Ets1 repression.

    Evidence X-ray crystallography of the Runx1/Ets1/TCRα-DNA ternary complex with structure-guided mutagenesis

    PMID:24646888

    Open questions at the time
    • Generality of this allosteric mechanism to other RUNX1 partners untested
    • Does not address corepressor-mode structural transitions
  10. 2017 High

    Defined CBFβ heterodimerization through the Runt domain as the transforming requirement for RUNX1-ETO and established post-translational control by STUB1 ubiquitination/export.

    Evidence Runt-domain point mutants in murine leukemia models; E3-ligase binding, ubiquitination, localization, and growth assays

    PMID:19179469 PMID:28360416 PMID:28536267

    Open questions at the time
    • Why CBFβ is needed for leukemia but dispensable for myeloproliferation mechanistically unresolved
    • STUB1 regulation of native RUNX1 in vivo not tested
  11. 2017 Medium

    Connected oncogenic signaling and metabolic context to RUNX1 activity: FLT3-ITD phosphorylates and cooperates with RUNX1 (target HHEX), CDK6 kinase suppresses RUNX1 to block beige adipogenesis, and nuclear FAK partners RUNX1 in carcinoma.

    Evidence Conditional KO in FLT3-ITD and CDK6-kinase-dead mice with ChIP for direct targets; Co-IP and ChIP in SCC tumor model

    PMID:28213513 PMID:28807942 PMID:29523786

    Open questions at the time
    • Direct kinase-substrate vs indirect effects on RUNX1 not always disentangled
    • FAK-RUNX1 interaction shown by single-lab Co-IP
  12. 2019 High

    Showed that EZH1 methylates AML1-ETO at Lys43 to augment its repressive activity, identifying a chromatin-modifier dependency of the fusion oncoprotein.

    Evidence Co-IP, in vitro methylation, K43 mutagenesis, EZH1 knockdown, and xenograft

    PMID:31699991

    Open questions at the time
    • Whether native RUNX1 is similarly methylated not addressed
    • Genome-wide consequences of K43 methylation not mapped
  13. 2020 High

    Resolved direct RUNX1-associated gene networks repressed by AML1-ETO using rapid degradation, showing fusion removal triggers a differentiation cascade; CHD7 acts as a brake on RUNX1-driven HSPC expansion.

    Evidence Auxin-inducible degron with TT-seq and CUT&RUN; Co-IP, ChIP-seq and genetic disruption of CHD7 in fish and mouse

    PMID:32883883 PMID:33382982

    Open questions at the time
    • Hierarchy of primary vs secondary targets in the cascade partially defined
    • Mechanism of CHD7 restraint on RUNX1 occupancy unclear
  14. 2021 Medium

    Established RNA- and partner-dependent control of RUNX1 output: the lncRNA LOUP recruits RUNX1 to loop the PU.1 locus, and dominant-negative germline variants reprogram lineage output to cause T-ALL.

    Evidence RNA-protein screen, chromatin conformation, ChIP-seq and LOUP perturbation; CD34+ lineage assays, ChIP-seq, and mouse T-ALL induction

    PMID:33971010 PMID:34166225

    Open questions at the time
    • How LOUP physically tethers RUNX1 not structurally defined
    • Why distinct variants produce divergent binding patterns mechanistically open
  15. 2022 High

    Extended RUNX1 function to niche maintenance and fibrosis, showing it prevents fibrotic conversion of HSC niches and drives TGF-β-induced myofibroblast differentiation via HuR-stabilized mRNA.

    Evidence Conditional Runx1/Runx2 KO in CAR cells with histology; siRNA, RIP for HuR-RUNX1 mRNA, and bleomycin lung fibrosis model

    PMID:35048404 PMID:35551452

    Open questions at the time
    • Anti-fibrotic vs pro-fibrotic roles appear cell-type-specific and not reconciled
    • Direct RUNX1 fibrotic target genes incompletely defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How RUNX1 switches between activator and repressor states at specific loci, and how its post-translational modifications are integrated to set context-specific target selection genome-wide, remains unresolved.
  • No unified model linking PTM state to activator/repressor choice
  • Structural basis of corepressor-mode complexes not solved
  • Determinants of cell-type-specific enhancer selection unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 5 GO:0140097 catalytic activity, acting on DNA 1
Localization
GO:0005654 nucleoplasm 3 GO:0005634 nucleus 2
Pathway
R-HSA-1643685 Disease 7 R-HSA-1266738 Developmental Biology 4 R-HSA-168256 Immune System 4 R-HSA-4839726 Chromatin organization 4 R-HSA-74160 Gene expression (Transcription) 4
Partners
CBFBCHD7EBF1EP300ETS1EZH1GATA1STUB1
Complex memberships
core-binding factor (RUNX1/CBFβ)

Evidence

Reading pass · 35 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 Cbfa2 (RUNX1) is required for definitive hematopoiesis (erythropoiesis and myelopoiesis) but not primitive erythropoiesis; Cbfa2-null mice die at E11.5-12.5 with hemorrhaging in the CNS and complete absence of definitive hematopoietic progenitors, demonstrating that DNA-binding-competent RUNX1 is essential for establishing the definitive hematopoietic program. Germline knockout mouse (Cbfa2-null); embryological analysis of hematopoietic progenitors Proceedings of the National Academy of Sciences of the United States of America High 8622955
1999 RUNX1 (CBFA2) is required for the formation of intra-aortic hematopoietic clusters from hemogenic endothelium in the AGM region; Cbfa2-expressing endothelial cells are specifically located in the ventral aorta and vitelline/umbilical arteries, and Cbfa2 maintains its own expression in this endothelium. Cbfa2-null mouse analysis; in situ expression mapping; endothelial cell lineage studies Development (Cambridge, England) High 10226014
1999 Haploinsufficiency of CBFA2 (RUNX1) causes familial platelet disorder with predisposition to AML (FPD/AML); heterozygous nonsense mutations, intragenic deletions, or missense mutations at conserved Runt domain residues (R166, R201) co-segregate with disease, and affected individuals show decreased megakaryocyte colony formation, demonstrating that RUNX1 dosage directly controls megakaryopoiesis. Mutational analysis of FPD/AML pedigrees; bone marrow megakaryocyte colony formation assays Nature genetics High 10508512
2003 RUNX1 physically interacts with GATA-1 and cooperates with CBFβ and GATA-1 to activate a megakaryocytic promoter; enforced RUNX1 expression enhances megakaryocytic integrin (αIIb, α2) induction. The leukemic RUNX1-ETO fusion protein potently represses GATA-1-mediated transactivation. Co-immunoprecipitation (physical interaction); luciferase reporter/cotransfection (functional cooperation); retroviral overexpression in K562 cells with flow cytometric readout Blood Medium 12576332
2006 RUNX1 (AML1) serines 276 and 303 are phosphorylated by cyclin-dependent kinases Cdk1/cyclin B and Cdk2/cyclin A in vitro; this phosphorylation promotes APC/Cdc20-mediated proteasomal degradation of RUNX1. Non-phosphorylatable RUNX1-4A is more stable and resistant to Cdc20-APC degradation, whereas phosphomimetic RUNX1-4D is efficiently targeted by both Cdc20 and Cdh1. In vitro kinase assay with purified Cdk1/cyclin B and Cdk2/cyclin A; CDK inhibitor treatment in vivo; site-directed mutagenesis (AML1-4A, AML1-4D); protein stability assays with Cdc20/Cdh1 overexpression Molecular and cellular biology High 17015473
2006 RUNX1 deficiency in macrophage differentiation leads to increased corepressor (Eto2, Sin3A, Hdac2) co-immunoprecipitation with PU.1, decreased histone acetylation at Mcsfr and Gmcsfr promoters, and impaired PU.1-driven activation of myeloid differentiation genes. Full-length RUNX1 excludes corepressors from the PU.1 complex, while leukemia-associated truncated RUNX1 variants permit corepressor interaction. Co-immunoprecipitation; chromatin immunoprecipitation (histone acetylation); Runx1 shRNA knockdown in macrophage differentiation model; cotransfection with truncated RUNX1 variants; HDAC inhibitor rescue experiments Blood High 21518930
2009 CBFβ is required for AML1-ETO's ability to inhibit granulocyte differentiation, enhance clonogenic potential of primary bone marrow cells, and cooperate with TEL-PDGFβR to generate AML in mice; Runt domain mutations that disrupt CBFβ heterodimerization (but not DNA binding) abrogate these activities, validating the Runt domain/CBFβ interaction as a therapeutic target. Site-directed mutagenesis of the Runt domain; bone marrow colony assays; retroviral transduction mouse leukemia model; differentiation assays Blood High 19179469
2008 The AML1/RUNX1 DNA-binding (Runt) domain and ETO NHR2 dimerization domain are each critical for AML1-ETO9a leukemogenesis in mice; removal of the Runt domain or NHR2 domain abolishes leukemia induction, while NHR1 is dispensable but influences latency. Retroviral transduction of domain-deletion mutants into mouse bone marrow; murine bone marrow transplantation leukemia model Blood High 19036704
2014 Crystal structure of the ternary Runx1(1-242)/Ets1(296-441)/TCRα enhancer DNA complex reveals that the Ets1-interacting domain of Runx1 binds the Ets1 DNA-binding domain and displaces the entire autoinhibitory module of Ets1, providing the structural basis for Runx1-mediated Ets1 activation. Structure-guided Runx1 mutants confirmed the critical role of direct Ets1•Runx1 interaction. X-ray crystallography of ternary complex; structure-guided mutagenesis; DNA-binding and transcriptional assays Leukemia High 24646888
1998 A replication activation domain (RAD, aa 302-371) of PEBP2αB1 (RUNX1/AML1) associates with the nuclear matrix, can stimulate polyomavirus DNA replication through its cognate binding site, and competes for nuclear matrix association; AML1-ETO lacks this region, also localizes to the nuclear matrix, and inhibits RUNX1-stimulated DNA replication proportional to displacement of RUNX1 from the nuclear matrix. Nuclear matrix fractionation; GAL4-RAD fusion reporter constructs; DNA replication assay; competition binding studies Molecular and cellular biology Medium 9632801
2006 RUNX1 induces mesenchymal stem cell commitment to early chondrogenesis; retroviral overexpression of Runx1 in embryonic mesenchymal cells potently induces early chondrocyte markers (type II collagen, alkaline phosphatase) but not the hypertrophy marker type X collagen, while RNAi-mediated knockdown inhibits these markers and subsequently inhibits type X collagen. Retroviral overexpression of Runx1; siRNA knockdown; real-time RT-PCR; immunohistochemistry in limb bud micromass cultures Journal of bone and mineral research Medium 16059634
2010 Runx1 and Runx2 cooperatively regulate sternal morphogenesis and commitment of mesenchymal cells to chondrocytes through direct induction of Sox5 and Sox6 expression, which in turn drives Col2a1 expression; mesenchymal-specific Runx1/Runx2 double-knockout mice completely lack a sternum with impaired chondrocyte commitment, while single knockouts show only a delay. Conditional (Prx1-Cre) Runx1/Runx2 single and double knockout mice; in situ hybridization; promoter activity assays Development (Cambridge, England) High 20181744
2006 Notch1 signaling upregulates Runx1 expression in para-aortic splanchnopleural (P-Sp) hematopoietic progenitors; retroviral transfer of Runx1 rescues the defective hematopoietic potential of Notch1-null P-Sp cells, and Hes1 (a Notch effector) potentiates Runx1-mediated transactivation, placing Runx1 downstream of Notch1 in definitive hematopoiesis. Notch1-null mouse hematopoietic rescue by retroviral Runx1 transfer in OP9 co-culture; cotransfection reporter assays for Hes1/Runx1 cooperation Blood Medium 16888092
2010 Compound haploinsufficiency of Ebf1 and Runx1 in mice impairs B cell lineage progression at multiple bone marrow stages; enforced co-expression of EBF1 and RUNX1 in terminally differentiated plasmacytoma cells synergistically activates multiple early B cell-specific genes, demonstrating functional cooperation between EBF1 and RUNX1 in B cell specification. Ebf1+/- Runx1+/- compound heterozygous mice; gene expression analysis; retroviral co-expression in plasmacytoma cells; flow cytometry Proceedings of the National Academy of Sciences of the United States of America Medium 20385820
2017 E3 ubiquitin ligase STUB1 binds RUNX1, induces its ubiquitination and proteasomal degradation predominantly in the nucleus, and promotes nuclear export of RUNX1, reducing its transcriptional activity; STUB1 also ubiquitinates RUNX1-RUNX1T1 and inhibits growth of RUNX1-RUNX1T1-expressing leukemia cells. High-throughput E3 ligase binding assay; co-immunoprecipitation; ubiquitination assay; immunofluorescence; STUB1 overexpression/knockdown with cell growth readout The Journal of biological chemistry Medium 28536267
2016 RUNX1 auto-regulates its own P1 promoter: RUNX1 protein binds conserved RUNX motifs within the P1 promoter 5'UTR (demonstrated by ChIP), mutation/deletion of these sites enhances basal promoter activity, and overexpression of RUNX1 in non-hematopoietic cells dose-dependently activates the P1 promoter. SCL is also recruited to these RUNX motifs and regulates P1 promoter activity. Chromatin immunoprecipitation; luciferase reporter assays with site-directed mutagenesis; RUNX1 overexpression; in silico promoter analysis PloS one Medium 26901859
2015 PRMT1-mediated arginine methylation of RUNX1 at R206 and R210 (RTAMR motif) inhibits corepressor binding to RUNX1, enhancing its transcriptional activity; knock-in mice with non-methylable RUNX1 (KTAMK) show impaired peripheral CD4+ T cell homeostasis but normal definitive hematopoiesis and platelet production. Knock-in mouse model (RUNX1 R206K/R210K); flow cytometry of lymphoid compartments; biochemical analysis of corepressor interaction British journal of haematology Medium 26010396
2017 FLT3-ITD directly impacts RUNX1 activity by upregulating and phosphorylating RUNX1, and RUNX1 cooperates with FLT3-ITD to induce AML; inactivating RUNX1 in FLT3-ITD tumors releases differentiation block and downregulates ribosome biogenesis genes. HHEX is identified as a direct transcriptional target of RUNX1 activated by FLT3-ITD stimulation. Conditional Runx1 knockout in FLT3-ITD mouse model; ChIP for HHEX as direct target; retroviral co-expression; gene expression analysis The Journal of experimental medicine Medium 28213513
2019 EZH1 WD domain physically binds the AML1-ETO NHR1 domain and methylates AML1-ETO at lysine 43 (Lys43) via its SET domain; this methylation augments AML1-ETO-dependent repression of tumor suppressor genes. Loss of Lys43 methylation (point mutation or domain deletion) impairs AML1-ETO repressive activity, and EZH1 knockdown impairs survival of AML1-ETO cells in vitro and in vivo. Co-immunoprecipitation; in vitro methylation assay; site-directed mutagenesis (K43 mutation); domain deletion analysis; EZH1 knockdown with cell viability readout; in vivo xenograft Nature communications High 31699991
2013 Cohesin and CTCF regulate RUNX1 expression through direct binding at P1, P2 promoters, and intronic cis-regulatory elements; cohesin initiates runx1 expression in posterior lateral mesoderm and influences promoter use, while CTCF represses expression in tail bud cells. Cohesin depletion enhanced RUNX1 expression in a human leukemia cell line, suggesting conservation. ChIP for cohesin and CTCF binding; insulator assays in vivo (zebrafish); cohesin/CTCF depletion in zebrafish and human leukemia cells; RNA pol II ChIP Biochimica et biophysica acta Medium 24321385
2020 CHD7 physically interacts with RUNX1, and decreased RUNX1 occupancy correlates with loss of CHD7 localization; CHD7 suppresses RUNX1-induced expansion of HSPCs during development, providing a braking mechanism for hematopoietic differentiation. Co-immunoprecipitation (CHD7-RUNX1 physical interaction); ChIP-seq showing overlapping occupancy; CHD7 genetic disruption in zebrafish and mouse with HSPC/lineage phenotyping Proceedings of the National Academy of Sciences of the United States of America Medium 32883883
2013 Genome-wide ChIP-seq in primary megakaryocytes identifies Runx1/p300 co-occupied enhancers enriched for RUNX, ETS, and GATA motifs that control megakaryocytic maturation genes; Runx1-specific conditional knockout in megakaryocytes impairs their maturation, and specific Runx1/p300 co-bound regions of Nfe2 and Selp were validated as functional enhancers by in vivo transgenesis. Megakaryocyte-specific Runx1 conditional knockout; ChIP-seq (Runx1 and p300); transfection mutagenesis; in vivo transgenic enhancer assay PloS one High 23717578
2021 The lncRNA LOUP, identified as a RUNX1-interacting RNA at the PU.1 locus, recruits RUNX1 to both the PU.1 enhancer and promoter to form an active chromatin loop driving myeloid differentiation; RUNX1-ETO limits chromatin accessibility at the LOUP locus, suppressing LOUP and PU.1 expression in t(8;21) AML. Genome-wide RNA-protein interaction screen; chromatin conformation assay (loop formation); RUNX1 ChIP-seq; LOUP knockdown/overexpression with differentiation and growth readouts; ATAC-seq Blood Medium 33971010
2020 AML1-ETO removal leads to rapid derepression of a core gene network that is associated with RUNX1 DNA binding, triggering a transcription cascade resulting in myeloid differentiation; direct gene targets of AML1-ETO were identified by combining rapid protein degradation with nascent transcript analysis and CUT&RUN genome-wide binding. Auxin-inducible degron for rapid AML1-ETO degradation; nascent transcript analysis (TT-seq); CUT&RUN for genome-wide binding Molecular cell High 33382982
2003 A heterozygous CBFA2 mutation (splice acceptor site deletion causing frameshift in Runt domain) is associated with decreased platelet PKC-θ expression and impaired receptor-mediated GPIIb-IIIa activation and pleckstrin phosphorylation, demonstrating that RUNX1-regulated proteins (including PKC-θ) are required for inside-out signaling in platelets. Patient mutation sequencing; immunoblotting for downstream proteins; platelet functional assays (aggregation, phosphorylation) Blood Medium 14525764
2018 CDK6 kinase activity suppresses RUNX1 expression and thereby inhibits beige adipocyte formation; loss of CDK6 or its kinase domain increases RUNX1, which transcriptionally activates Ucp-1 and Pgc1α by binding their proximal promoters; ablation of RUNX1 in CDK6-kinase-dead cells reverses the enhanced beige adipogenesis phenotype. CDK6 kinase-dead knock-in mice; RUNX1 conditional knockout in adipocyte precursors; ChIP showing RUNX1 binding to Ucp-1/Pgc1α promoters; rescue experiments Nature communications High 29523786
1997 ETV6/CBFA2 (TEL/AML1) fusion protein inhibits CBFA2B-mediated activation of the MCSFR promoter; inhibition requires both the ETS DNA-binding domain of ETV6 and the ETS/C/EBPα binding sites on the promoter, indicating inhibition depends on protein-protein interactions rather than direct DNA competition alone. Deletion of the HLH region from ETV6/CBFA2 decreased but did not abrogate inhibition. Luciferase reporter assays; promoter mutational analysis; deletion mutagenesis of ETV6 and ETV6/CBFA2 domains Proceedings of the National Academy of Sciences of the United States of America Medium 9050885
2017 Nuclear FAK forms a molecular complex with Runx1 in squamous cell carcinoma cells and regulates Runx1-dependent transcription of IGFBP3, controlling cell-cycle progression and tumor growth in vivo; FAK interacts with Runx1-regulatory proteins including Sin3a and other epigenetic modifiers. Co-immunoprecipitation (FAK-Runx1 nuclear complex); ChIP; siRNA knockdown; murine SCC tumor model Cancer research Medium 28807942
2022 Runx1 is predominantly expressed in CAR (CXCL12-abundant reticular) cells in bone marrow niches; conditional deletion of both Runx1 and Runx2 in CAR cells leads to increased fibrosis, bone formation, and markedly reduced HSCs; in vitro, Runx1 is induced by Foxc1 and decreases fibrotic gene expression in CAR cells, demonstrating that Runx1 prevents fibrotic conversion of HSC niches. Conditional double-knockout mice (Runx1/Runx2 in CAR cells); histological analysis; in vitro Foxc1-mediated induction; gene expression analysis of fibrotic markers Nature communications High 35551452
2021 Dominant-negative germline RUNX1 variants associated with T-ALL repress differentiation into erythroid, megakaryocyte, and T cell lineages while promoting myeloid development in human CD34+ cells; ChIP-seq in T-ALL models shows distinctive RUNX1 binding patterns for variant proteins; co-introduction of RUNX1 variant and JAK3 mutation in HSPCs gives rise to T-ALL in mice. Ectopic expression in human CD34+ cells with lineage differentiation assays; ChIP-seq; mouse HSPC transduction with T-ALL induction The Journal of clinical investigation High 34166225
2017 RUNX1-EVI1 and RUNX1-ETO fusion proteins, despite sharing the same RUNX1 DNA-binding domain, display distinct genome-wide binding patterns, different chromatin landscapes, and dependence on different transcription factors (GATA2 for RUNX1-EVI1; RUNX1 for RUNX1-ETO), establishing that the fusion partner determines the transcriptional network rather than the DNA-binding domain alone. ChIP-seq; ATAC-seq; RNA-seq; RNAi screens for transcription factor dependencies in patient-derived AML cells Cell reports High 28538183
2017 CBFβ heterodimerization with AML1/ETO (via Runt domain) is required for leukemogenesis but not myeloproliferation; disruption of CBFβ interaction abolishes both AML1-ETO leukemia induction and long-term replating but preserves myeloproliferation; CBFβ interaction is required for derepression of Notch target genes by AML1-ETO. Runt domain point mutations disrupting CBFβ interaction; murine bone marrow transplantation model; myeloproliferation and leukemia induction assays Leukemia High 28360416
2005 RUNX1 enhances gene transcription by interacting with transcriptional coactivators p300 and CREB-binding protein, and represses gene transcription by interacting with corepressors mSin3A, TLE (Groucho homolog), and histone deacetylases; these interactions are context-dependent. Co-immunoprecipitation and cotransfection reporter assays (as reviewed from primary experimental studies) International journal of hematology Low 16105753
2022 TGF-β stimulation of human lung fibroblasts increases RUNX1 expression through enhanced mRNA stability mediated by selective interaction with the RNA-binding protein HuR; RUNX1 knockdown reduces differentiation of fibroblasts into myofibroblasts (reduced α-SMA, FN1, COL1A1), and RUNX1 inhibition limits bleomycin-induced lung fibrosis in mice. siRNA knockdown; TGF-β stimulation with expression analysis; RIP (RNA immunoprecipitation) for HuR-RUNX1 mRNA interaction; bleomycin mouse model Journal of cellular physiology Medium 35048404
2016 RUNX1 epigenetically represses the miR144/451 cluster during megakaryopoiesis; the leukemogenic RUNX1/ETO fusion protein transcriptionally represses miR144/451 pre-microRNA. Inhibition of RUNX1/ETO in Kasumi1 cells and primary t(8;21) AML patient samples leads to upregulation of miR144/451. ChIP (epigenetic repression); reporter and expression assays; RUNX1/ETO inhibition in cell lines and primary patient samples PLoS genetics Medium 26990877

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis. Proceedings of the National Academy of Sciences of the United States of America 1029 8622955
1999 Haploinsufficiency of CBFA2 causes familial thrombocytopenia with propensity to develop acute myelogenous leukaemia. Nature genetics 891 10508512
1999 Cbfa2 is required for the formation of intra-aortic hematopoietic clusters. Development (Cambridge, England) 557 10226014
2003 RUNX1 and GATA-1 coexpression and cooperation in megakaryocytic differentiation. Blood 273 12576332
2004 Point mutations in the RUNX1/AML1 gene: another actor in RUNX leukemia. Oncogene 222 15156185
2012 RUNX1 and RUNX1-ETO: roles in hematopoiesis and leukemogenesis. Frontiers in bioscience (Landmark edition) 134 22201794
2017 The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia. Molecular cancer 112 28724437
2005 Runx1/AML1/Cbfa2 mediates onset of mesenchymal cell differentiation toward chondrogenesis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 112 16059634
2003 New mechanisms of AML1 gene alteration in hematological malignancies. Leukemia 107 12529654
2008 AML1-ETO reprograms hematopoietic cell fate by downregulating scl expression. Development (Cambridge, England) 103 18156164
2001 A novel CBFA2 single-nucleotide mutation in familial platelet disorder with propensity to develop myeloid malignancies. Blood 103 11675361
2001 RUNX1/AML1: a central player in hematopoiesis. International journal of hematology 102 11721959
1998 CBFA2(AML1) translocations with novel partner chromosomes in myeloid leukemias: association with prior therapy. Blood 102 9763573
2001 The expression of ETV6/CBFA2 (TEL/AML1) is not sufficient for the transformation of hematopoietic cell lines in vitro or the induction of hematologic disease in vivo. Cancer genetics and cytogenetics 95 11675129
2005 Overlapping expression of Runx1(Cbfa2) and Runx2(Cbfa1) transcription factors supports cooperative induction of skeletal development. Journal of cellular physiology 91 15389629
2019 RUNX1-targeted therapy for AML expressing somatic or germline mutation in RUNX1. Blood 85 31023702
2009 Cell cycle and developmental control of hematopoiesis by Runx1. Journal of cellular physiology 81 19235904
2006 AML1/Runx1 rescues Notch1-null mutation-induced deficiency of para-aortic splanchnopleural hematopoiesis. Blood 81 16888092
2011 RUNX1 translocations and fusion genes in malignant hemopathies. Future oncology (London, England) 79 21174539
2017 Identification of RUNX1 as a Mediator of Aberrant Retinal Angiogenesis. Diabetes 78 28400392
2010 Runx1 and Runx2 cooperate during sternal morphogenesis. Development (Cambridge, England) 77 20181744
2020 RUNX1: an emerging therapeutic target for cardiovascular disease. Cardiovascular research 76 32154891
2020 Secondary leukemia in patients with germline transcription factor mutations (RUNX1, GATA2, CEBPA). Blood 74 32430494
2022 RUNX1 and cancer. Biochimica et biophysica acta. Reviews on cancer 72 35271994
2018 RUNX1 and the endothelial origin of blood. Experimental hematology 70 30391350
2006 AML1/RUNX1 phosphorylation by cyclin-dependent kinases regulates the degradation of AML1/RUNX1 by the anaphase-promoting complex. Molecular and cellular biology 69 17015473
2017 RUNX1 Mutations in Inherited and Sporadic Leukemia. Frontiers in cell and developmental biology 68 29326930
2020 High frequency of germline RUNX1 mutations in patients with RUNX1-mutated AML. Blood 67 32315381
2018 CDK6 inhibits white to beige fat transition by suppressing RUNX1. Nature communications 65 29523786
2006 Decreased platelet expression of myosin regulatory light chain polypeptide (MYL9) and other genes with platelet dysfunction and CBFA2/RUNX1 mutation: insights from platelet expression profiling. Journal of thrombosis and haemostasis : JTH 65 17059412
2004 Molecular mechanisms of leukemogenesis by AML1/EVI-1. Oncogene 64 15156182
2005 Runx1/AML1 in normal and abnormal hematopoiesis. International journal of hematology 63 16105753
2003 Association of CBFA2 mutation with decreased platelet PKC-theta and impaired receptor-mediated activation of GPIIb-IIIa and pleckstrin phosphorylation: proteins regulated by CBFA2 play a role in GPIIb-IIIa activation. Blood 62 14525764
2002 AML1 gene over-expression in childhood acute lymphoblastic leukemia. Leukemia 62 11960347
1997 Functional characterization of ETV6 and ETV6/CBFA2 in the regulation of the MCSFR proximal promoter. Proceedings of the National Academy of Sciences of the United States of America 61 9050885
2020 Definition of a small core transcriptional circuit regulated by AML1-ETO. Molecular cell 59 33382982
2016 RUNX1 Regulates Migration, Invasion, and Angiogenesis via p38 MAPK Pathway in Human Glioblastoma. Cellular and molecular neurobiology 59 28012022
2004 Familial mutations of the transcription factor RUNX1 (AML1, CBFA2) predispose to acute myeloid leukemia. Leukemia & lymphoma 59 15061191
2003 The role of a Runt domain transcription factor AML1/RUNX1 in leukemogenesis and its clinical implications. Critical reviews in oncology/hematology 58 12604126
2018 RUNX1: A Regulator of NF-kB Signaling in Pulmonary Diseases. Current protein & peptide science 57 28990531
2014 Posttranslational modifications of RUNX1 as potential anticancer targets. Oncogene 57 25263451
2017 The Role of Runx1 in Embryonic Blood Cell Formation. Advances in experimental medicine and biology 56 28299650
2009 AML1/RUNX1 point mutation possibly promotes leukemic transformation in myeloproliferative neoplasms. Blood 55 19850737
2005 Somatic point mutations in RUNX1/CBFA2/AML1 are common in high-risk myelodysplastic syndrome, but not in myelofibrosis with myeloid metaplasia. European journal of haematology 50 15613106
2000 Potential roles for RUNX1 and its orthologs in determining hematopoietic cell fate. Seminars in cell & developmental biology 50 11105897
2017 Nuclear FAK and Runx1 Cooperate to Regulate IGFBP3, Cell-Cycle Progression, and Tumor Growth. Cancer research 49 28807942
1996 Correlation between the ETV6/CBFA2 (TEL/AML1) fusion gene and karyotypic abnormalities in children with B-cell precursor acute lymphoblastic leukemia. Genes, chromosomes & cancer 48 8913730
2008 RUNX1/AML1 DNA-binding domain and ETO/MTG8 NHR2-dimerization domain are critical to AML1-ETO9a leukemogenesis. Blood 46 19036704
2009 CBFbeta is critical for AML1-ETO and TEL-AML1 activity. Blood 45 19179469
2009 Molecular pathways mediating MDS/AML with focus on AML1/RUNX1 point mutations. Journal of cellular physiology 45 19334039
2017 RUNX1-ETO Leukemia. Advances in experimental medicine and biology 44 28299657
2011 RUNX1 regulates corepressor interactions of PU.1. Blood 43 21518930
2010 Compound haploinsufficiencies of Ebf1 and Runx1 genes impede B cell lineage progression. Proceedings of the National Academy of Sciences of the United States of America 43 20385820
2002 Runx1/AML1 in leukemia: disrupted association with diverse protein partners. Leukemia research 43 11792409
2017 RUNX1-ETO and RUNX1-EVI1 Differentially Reprogram the Chromatin Landscape in t(8;21) and t(3;21) AML. Cell reports 42 28538183
2003 Role of AML1/Runx1 in the pathogenesis of hematological malignancies. Cancer science 41 14556655
2001 Point mutations of the RUNx1/AML1 gene in sporadic and familial myeloid leukemias. International journal of hematology 41 11721958
2021 Germline RUNX1 variation and predisposition to childhood acute lymphoblastic leukemia. The Journal of clinical investigation 39 34166225
2020 TNF-α signaling regulates RUNX1 function in endothelial cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 33135824
1994 The AML1 and ETO genes in acute myeloid leukemia with a t(8;21). Leukemia & lymphoma 38 7812194
2021 AML1/ETO and its function as a regulator of gene transcription via epigenetic mechanisms. Oncogene 37 34331016
2017 RUNX1 cooperates with FLT3-ITD to induce leukemia. The Journal of experimental medicine 37 28213513
2014 Structural basis of Ets1 activation by Runx1. Leukemia 37 24646888
2003 AML1 interconnected pathways of leukemogenesis. Cancer investigation 37 12643014
2022 Runx1 and Runx2 inhibit fibrotic conversion of cellular niches for hematopoietic stem cells. Nature communications 35 35551452
2009 RUNX1 and its fusion oncoprotein derivative, RUNX1-ETO, induce senescence-like growth arrest independently of replicative stress. Oncogene 35 19448675
2019 RUNX1 mutations promote leukemogenesis of myeloid malignancies in ASXL1-mutated leukemia. Journal of hematology & oncology 34 31640815
2013 Cohesin and CTCF differentially regulate spatiotemporal runx1 expression during zebrafish development. Biochimica et biophysica acta 34 24321385
2006 AML1/Runx1 as a versatile regulator of hematopoiesis: regulation of its function and a role in adult hematopoiesis. International journal of hematology 34 16926135
1998 The capacity of polyomavirus enhancer binding protein 2alphaB (AML1/Cbfa2) to stimulate polyomavirus DNA replication is related to its affinity for the nuclear matrix. Molecular and cellular biology 34 9632801
2009 RUNX1 translocations in malignant hemopathies. Anticancer research 33 19414342
2001 Amplification of the AML1(CBFA2) gene on ring chromosomes in a patient with acute myeloid leukemia and a constitutional ring chromosome 21. Cancer genetics and cytogenetics 33 11165321
2022 Inhibition of RUNX1 blocks the differentiation of lung fibroblasts to myofibroblasts. Journal of cellular physiology 30 35048404
2021 RUNX1/RUNX1T1 mediates alternative splicing and reorganises the transcriptional landscape in leukemia. Nature communications 30 33483506
2007 Gatekeeper function of the RUNX1 transcription factor in acute leukemia. Blood cells, molecules & diseases 30 17920312
2017 KSRP specifies monocytic and granulocytic differentiation through regulating miR-129 biogenesis and RUNX1 expression. Nature communications 29 29127290
2017 The ubiquitin ligase STUB1 regulates stability and activity of RUNX1 and RUNX1-RUNX1T1. The Journal of biological chemistry 28 28536267
2017 Loss of RUNX1 is associated with aggressive lung adenocarcinomas. Journal of cellular physiology 27 28926105
2021 Myeloid lncRNA LOUP mediates opposing regulatory effects of RUNX1 and RUNX1-ETO in t(8;21) AML. Blood 26 33971010
2018 Rasip1 is a RUNX1 target gene and promotes migration of NSCLC cells. Cancer management and research 26 30349386
2016 Transcriptional Auto-Regulation of RUNX1 P1 Promoter. PloS one 26 26901859
2010 The role of Runx1/AML1 and Evi-1 in the regulation of hematopoietic stem cells. Journal of cellular physiology 26 19847803
2005 Increased dosage of the RUNX1/AML1 gene: a third mode of RUNX leukemia? Critical reviews in eukaryotic gene expression 26 16390318
2017 Myeloid neoplasms with germ line RUNX1 mutation. International journal of hematology 25 28534116
2012 Deregulation of RAD21 and RUNX1 expression in endometrial cancer. Oncology letters 25 23205091
2016 Taking the Leap: Runx1 in the Formation of Blood from Endothelium. Current topics in developmental biology 24 27137656
2004 SLC22A4 and RUNX1: identification of RA susceptible genes. Journal of molecular medicine (Berlin, Germany) 24 15184985
2017 Runx1 Structure and Function in Blood Cell Development. Advances in experimental medicine and biology 23 28299651
2001 Novel cryptic, complex rearrangements involving ETV6-CBFA2 (TEL-AML1) genes identified by fluorescence in situ hybridization in pediatric patients with acute lymphoblastic leukemia. Genes, chromosomes & cancer 23 11550288
2020 RUNX1 Dosage in Development and Cancer. Molecules and cells 22 31991535
2020 The RUNX1/RUNX1T1 network: translating insights into therapeutic options. Experimental hematology 22 33217477
2017 Heterodimerization of AML1/ETO with CBFβ is required for leukemogenesis but not for myeloproliferation. Leukemia 22 28360416
2005 AML1-FOG2 fusion protein in myelodysplasia. Blood 22 15705784
2017 Mechanism of ETV6-RUNX1 Leukemia. Advances in experimental medicine and biology 21 28299659
2020 CHD7 and Runx1 interaction provides a braking mechanism for hematopoietic differentiation. Proceedings of the National Academy of Sciences of the United States of America 20 32883883
2016 MiR144/451 Expression Is Repressed by RUNX1 During Megakaryopoiesis and Disturbed by RUNX1/ETO. PLoS genetics 20 26990877
2015 Loss of RUNX1/AML1 arginine-methylation impairs peripheral T cell homeostasis. British journal of haematology 20 26010396
2019 Protein lysine 43 methylation by EZH1 promotes AML1-ETO transcriptional repression in leukemia. Nature communications 19 31699991
2013 Cell-autonomous function of Runx1 transcriptionally regulates mouse megakaryocytic maturation. PloS one 19 23717578
1996 Rearrangement of the AML1/CBFA2 gene in myeloid leukemia with the 3;21 translocation: expression of co-existing multiple chimeric genes with similar functions as transcriptional repressors, but with opposite tumorigenic properties. Current topics in microbiology and immunology 19 8585955

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