• Like other transcription factors, the RUNX1 protein attaches (binds) to specific regions of DNA and helps control the activity of particular genes. (medlineplus.gov)
  • The RUNX1 protein turns on (activates) genes that help control the development of blood cells (hematopoiesis). (medlineplus.gov)
  • It belongs to the Runt-related transcription factor (RUNX) family of genes which are also called core binding factor-α (CBFα). (wikipedia.org)
  • Identification of novel Runx1 (AML1) translocation partner genes SH3D19, YTHDf2, and ZNF687 in acute myeloid leukemia. (atlasgeneticsoncology.org)
  • Co-expression of two mutant genes increased myeloid stem cells in animal model, suggesting that cooperation of RUNX1 and ASXL1 mutations played a critical role in leukemia transformation. (biomedcentral.com)
  • In this study, we show that increased expression of Runt related transcription factor 1 (RUNX1) maintains undifferentiated state of CSC-like SP cells through upregulation of inhibitors of DNA binding/differentiation genes (ID1 and ID3) in late cisplatin-paclitaxel resistant cells. (techscience.com)
  • The protein-protein interaction network analysis of 397 upregulated genes in RUNX1-high samples of TCGA data show significant enrichment of pathways known to negatively regulate CSC differentiation. (techscience.com)
  • Further analysis revealed that a lower AR occupancy was accompanied by a reduction in FoxA1 binding at regulatory regions of AR-dependent genes. (oncotarget.com)
  • Runx factors bind DNA and co-factors to activate or repress genes crucial for bone formation, hematopoiesis, and neuronal development. (elsevierpure.com)
  • A novel complex, RUNX1-MYEF2, represses hematopoietic genes in erythroid cells. (ox.ac.uk)
  • Functional analysis shows that a subset of the target genes is suppressed by RUNX1 via the newly identified partner MYEF2. (ox.ac.uk)
  • Our patient had MDS with pathogenic mutations of the RUNX1 , SRSF2 , ASXL1 , and TET2 genes and developed 1q JTs at the time of progression from MDS to AML. (biomedcentral.com)
  • Here, we describe a patient with AML that progressed from a myelodysplastic syndrome (MDS) with pathogenic mutations of the RUNX1 , SRSF2 , ASXL1 , and TET2 genes in association with development of 1q JTs, which supports that the formation of 1q JTs may involve multiple stages and that 1q JTs may represent a very high-risk cytogenetic abnormality with transformation to AML. (biomedcentral.com)
  • The runx1 and c-fms genes showed an identical pattern of expression in mature macrophages. (monocyte.eu)
  • Huang G, Shigesada K, Ito K, Wee HJ, Yokomizo T, Ito Y. Dimerization with PEBP2beta protects RUNX1/AML1 from ubiquitin-proteasome-mediated degradation. (medlineplus.gov)
  • Runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1) or core-binding factor subunit alpha-2 (CBFA2) is a protein that in humans is encoded by the RUNX1 gene. (wikipedia.org)
  • As a member of the core-binding factor family of transcription factors, RUNX1, also known as acute myeloid leukemia 1 protein (AML1), modulates cell proliferation, differentiation, and survival. (lipexogen.com)
  • Germline mutations in the gene AML1 ( RUNX1, CBFA2 ) occur in the familial platelet disorder with predisposition for AML, an autosomal dominant disorder characterized by moderate thrombocytopenia, a defect in platelet function, and propensity to develop AML. (medscape.com)
  • Translocations and other types of mutations involving the RUNX1 gene have been associated with different types of leukemia and related blood disorders, including acute lymphoblastic leukemia (ALL), chronic myelomonocytic leukemia (CMML), familial platelet disorder with predisposition to acute myeloid leukemia, and myelodysplastic syndromes (MDS). (medlineplus.gov)
  • The RUNX1 gene mutations associated with these diseases are somatic mutations and are not inherited. (medlineplus.gov)
  • Mutations in RUNX1 are implicated in cases of breast cancer. (wikipedia.org)
  • Mice embryos with homozygous mutations on RUNX1 died at about 12.5 days. (wikipedia.org)
  • Previously, we observed that transcription factor RUNX1 mutations ( RUNX1 -MT) coexisted with ASXL1 -MT in CMML and at myeloid blast phase of chronic myeloid leukemia. (biomedcentral.com)
  • The contribution of RUNX1 mutations in the pathogenesis of myeloid transformation in ASXL1 -mutated leukemia, however, remains unclear. (biomedcentral.com)
  • At 9 months post-BMT, mice harboring combined RUNX1 and ASXL1 mutations developed disease characterized by marked splenomegaly, hepatomegaly, and leukocytosis with a shorter latency. (biomedcentral.com)
  • Mice transduced with both ASXL1 and RUNX1 mutations enhanced inhibitor of DNA binding 1 (ID1) expression in the spleen, liver, and bone marrow cells. (biomedcentral.com)
  • Bone marrow samples from CMML showed that ID1 overexpressed in coexisted mutations of RUNX1 and ASXL1 compared to normal control and either RUNX1 -MT or ASXL1 -MT samples. (biomedcentral.com)
  • Somatic RUNX1 mutations are found in approximately 10% of patients with de novo acute myeloid leukemia (AML), but are more common in secondary forms of myelodysplastic syndrome (MDS) or AML. (molcells.org)
  • How these RUNX1 mutations contribute to the pathobiology of secondary MDS/AML is still unknown. (molcells.org)
  • This mini-review focusses on the role of RUNX1 mutations as the most common secondary leukemogenic hit in MDS/AML evolving from severe congenital neutropenia (SCN). (molcells.org)
  • Why secondary RUNX1 mutations are associated with sMDS/AML and how they contribute to the pathogenesis of these conditions remains largely unclear. (molcells.org)
  • Myeloid mutation panel showed mutations in RUNX1 , SRSF2 , ASXL1 , and TET2 . (biomedcentral.com)
  • Myeloid mutation panel showed mutations in RUNX1 (Glu223Glyfs*16), SRSF2 (Pro95His), ASXL1 (Gln976*), and TET2 (Ser890*) (TruSight myeloid sequencing panel, Illumina, Inc.). He received several other unsuccessful therapies, with serial bone marrow testing showing no change in morphology, a normal karyotype, and no change in myeloid mutations. (biomedcentral.com)
  • The RUNX1:CBFB complex binds to four RUNX1 response elements in the promoter of the MYL9 gene, encoding Myosin regulatory light polypeptide 9, which functions as the regulatory subunit of the myosin complex (Jalagadugula et al. (reactome.org)
  • This protein interacts with another protein called core binding factor beta or CBFβ (produced from the CBFB gene), which helps RUNX1 bind to DNA and prevents it from being broken down. (medlineplus.gov)
  • RUNX1 - RUNX1T1 , CBFB - MYH11 ), in which AML can be diagnosed with a blast count of less than 20% without a specific cutoff value of blast percentage. (cap.org)
  • RUNX1 belongs to the runt domain family of transcription factors and regulates target gene expression through forming a heterodimeric DNA-binding complex with CBFB. (biolegend.com)
  • And we found that the inversion generates a fusion gene between the core binding factor beta gene, or CBFB , and MYH11 , the gene encoding smooth muscle myosin. (nih.gov)
  • RUNX1 is a transcription factor that regulates the differentiation of hematopoietic stem cells into mature blood cells. (wikipedia.org)
  • RUNX1 is also required for the differentiation of CD8+, Th17, and regulatory T cells. (biolegend.com)
  • Impaired differentiation of megakaryocytes and decreased circulating platelet count were observed in the absence of RUNX1. (biolegend.com)
  • These findings revealed that RUNX1 acts as a tumor suppressor for myeloid leukemia and is crucial for the development and terminal differentiation of several blood cell lineages 2,3 . (biolegend.com)
  • To evaluate the leukemogenic role of RUNX1-MT in ASXL1 -mutated cells, we co-expressed RUNX1 -MT (R135T) and ASXL1 -MT (R693X) in different cell lines and performed immunoblot, co-immunoprecipitation, gene expression microarray, quantitative RT-PCR, cell proliferation, differentiation, and clonogenic assays for in vitro functional analyses. (biomedcentral.com)
  • The expression of RUNX1 mutant in ASXL1 -mutated myeloid cells augmented proliferation, blocked differentiation, and increased self-renewal activity. (biomedcentral.com)
  • Intriguingly RUNX1 inhibition not only induces CSC differentiation but also downregulates anti-apoptotic protein BCL2 in both SP and NSP cells and potentiates cytotoxic effects of Cisplatin-Paclitaxel in chemoresistant EOC cells. (techscience.com)
  • Altogether, our data reveal new regulatory roles by RUNX1 to modulate CSC differentiation via ID1 and ID3 and to promote chemoresistance through BCL2 upregulation. (techscience.com)
  • We found that in vitro, this interaction alters the ability of RUNX1 to bind to DNA and to regulate a reporter gene, whereas in vivo, the expression of the isolated 8th zinc finger motif of EVI1 is sufficient to block the granulocyte colony-stimulating factor-induced differentiation of 32Dcl3 cells, leading to cell death. (lincoln.ac.uk)
  • Runt-related transcription factors (RUNXs), RUNX1-3, are the master regulators of development and differentiation and are all important to the development of immune cells. (bjbms.org)
  • This finding implied the possible key role of RUNX1 in the differentiation of IDH mutant subtypes as well as in the formation of tumor microenvironment (TME) infiltration signatures by monitoring IFNGR2. (bjbms.org)
  • RUNX1 is known to be an essential transcription factor for generating hematopoietic stem cells (HSC), but much less is known about its role in the downstream process of hematopoietic differentiation. (ox.ac.uk)
  • MYEF2 is bound in undifferentiated cells and is lost upon differentiation, whereas LSD1 is bound in differentiated cells. (ox.ac.uk)
  • The EM-3 cell line, which represents an early myeloid progenitor cell line, showed growth arrest with Runx1 expression in the absence of any detectable changes in cell differentiation. (monocyte.eu)
  • The RUNX1 gene provides instructions for making a protein called runt-related transcription factor 1 (RUNX1). (medlineplus.gov)
  • The full-length RUNX1 protein is encoded by 12 exons. (wikipedia.org)
  • These domains are necessary for RUNX1 to mediate DNA binding and protein-protein interactions respectively. (wikipedia.org)
  • The protein RUNX1 is composed of 453 amino acids. (wikipedia.org)
  • Soon after the discovery of the drosophila runt protein and the human RUNX1 protein, RUNX1's function was discovered. (wikipedia.org)
  • Runx1 was purified as a sequence-specific DNA-binding protein that regulated the disease specificity of the Moloney murine Leukemia virus. (wikipedia.org)
  • ADAM binding protein Eve-1 is required for ectodomain shedding of epidermal growth factor receptor ligands. (atlasgeneticsoncology.org)
  • RNA binding protein IGF2BP1 synergizes with ETV6-RUNX1 to drive oncogenic signaling in B-cell Acute Lymphoblastic Leukemia. (uclahealth.org)
  • The RNA-binding protein IGF2BP3 is critical for MLL-AF4-mediated leukemogenesis. (uclahealth.org)
  • RNA-binding protein IGF2BP3 targeting of oncogenic transcripts promotes hematopoietic progenitor proliferation. (uclahealth.org)
  • RUNX1 was first identified as a RUNX1-ETO fusion protein in acute myeloid leukemia (AML) and is frequently mutated in AML and myelodysplastic syndrome due to chromosomal translocation. (biolegend.com)
  • The encoded protein contains two different binding sites that are known to bind DNA and function as a regulator of gene transcription. (biolegend.com)
  • Moreover, the RUNX1 mutant protein was more stable than WT and increased HIF1-α and its target ID1 gene expression in ASXL1 mutant cells. (biomedcentral.com)
  • RUNX3 protein is a transcription factor, containing a highly conserved DNA binding domain which binds to a DNA core motif of 5′ pyGpyGGT 3′ designated as a "runt domain, RD" which shares a sequence similarity with D. melanogaster RUNX. (hindawi.com)
  • The interesting thing is that this fusion protein binds to another protein called RUNX1. (nih.gov)
  • Oncogenic transcription factors such as the leukemic fusion protein RUNX1/ETO, which drives t(8;21) acute myeloid leukemia (AML), constitute cancer-specific but highly challenging therapeutic targets. (prinsesmaximacentrum.nl)
  • In this study, we identified CoAA as a Runx2 binding protein. (elsevierpure.com)
  • We used a tagging strategy to show that RUNX1 interacts with two novel protein partners, LSD1 and MYEF2, in erythroid cells. (ox.ac.uk)
  • Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. (medlineplus.gov)
  • RUNX1 regulates CD4 gene transcription during multiple stages of T cell development and represses the CD4 gene in CD4-CD8- (double negative) T cells. (biolegend.com)
  • In this report, we demonstrate that Runx1 precisely regulates c-fms (CSF-1 receptor) gene expression. (monocyte.eu)
  • These findings suggest that Runx1 regulates growth and survival of myeloid cells and provide a novel insight into the role of Runx family gene translocations in leukemogenesis. (monocyte.eu)
  • A rearrangement (translocation) of genetic material involving the RUNX1 gene is found in approximately 7 percent of individuals with a form of blood cancer known as acute myeloid leukemia (AML). (medlineplus.gov)
  • His research has led to the identification of several non-coding RNA species and RNA-binding proteins that are important in acute leukemia. (uclahealth.org)
  • Exceptions are acute promyelocytic leukemia (APL) and core binding factor AML (i.e. (cap.org)
  • RUNX proteins form a heterodimeric complex with CBFβ which confers increased DNA binding and stability to the complex. (wikipedia.org)
  • In fact, the RUNX family is often referred to as α-subunits, together with binding of a common β-subunit CBFβ, RUNX can behave as heterodimeric transcription factors collectively called the core binding factors (CBFs). (wikipedia.org)
  • High-quality, lentiviral transcription factor (TF) reporter system that provides a sensitive fluorescent or luminescent readout for human/mouse RUNX family transcription factor 1 (RUNX1) transcriptional activity in mammalian cells. (lipexogen.com)
  • The RUNX1 reporter is constructed with tandem repeats of consensus RUNX1 DNA binding elements to read out its transcriptional activity. (lipexogen.com)
  • The reporter lentivirus is purified by PEG precipitation and sucrose gradient centrifugation, and is ideal for studying RUNX1 transcriptional activity in difficult-to-transfect cells including primary and/or thawed cells. (lipexogen.com)
  • Monitor transcriptional activity of RUNX1 in mammalian cells, screen for activators or inhibitors of RUNX1 transcriptional activity. (lipexogen.com)
  • RUNX1-Mediated Binding Site Directed DNA Demethylation is a Novel Mechanism of Hematopoietic Gene Activation. (nih.gov)
  • RUNX1-deficient mice fail to generate hematopoietic stem cells. (biolegend.com)
  • Monoallelic germline pathogenic variants in RUNX1 cause autosomal dominant familial platelet disorder with predisposition to myeloid malignancy (FPDMM). (eviq.org.au)
  • Individuals with a monoallelic RUNX1 germline pathogenic variant should be informed of the risk of platelet dysfunction, particularly during pregnancy and major surgery. (eviq.org.au)
  • Monoallelic RUNX1 germline pathogenic variants cause autosomal dominant FPDMM which typically presents with mild-to-moderate thrombocytopenia with normal-sized platelets, a functional platelet defect leading to prolonged bleeding and an increased risk of MDS and AL (more commonly AML, followed by T-ALL). (eviq.org.au)
  • purified Runx2, the homolog of Runx1. (wikipedia.org)
  • the binding affinity of RUNX1 and RUNX2 was significantly increased by association with CBFβ. (wikipedia.org)
  • The carboxy-terminus of CoAA is essential for binding the Runt domains of Runx1 and Runx2. (elsevierpure.com)
  • The translocation, written as t(8;21), combines genetic information from chromosome 21 and chromosome 8, fusing the RUNX1 gene on chromosome 21 with a gene on chromosome 8 called RUNX1T1 (also known as ETO ). (medlineplus.gov)
  • Additionally, core binding factor (CBF) is disrupted by the translocation of chromosomes 8 and 21. (mdanderson.org)
  • This balanced translocation generates the RUNX1-RUNX1T1 fusion gene on the derivative chromosome 8, resulting in t(8;21)(q22;q22.1). (mdanderson.org)
  • The correlation of RUNX1-RUNX1T1 gene generated on the derivative chromosome 8 will result in t(8;21)(q22;q22.1), a balanced translocation. (mdanderson.org)
  • Molecular pathogenesis of core binding factor leukemia: current knowledge and future prospects. (medlineplus.gov)
  • Chromosomal translocations involving the RUNX1 gene are associated with several types of leukemia including M2 AML. (wikipedia.org)
  • The present study demonstrated the biological and functional evidence for the critical role of RUNX1 -MT in ASXL1 -mutated leukemia in the pathogenesis of myeloid malignancies. (biomedcentral.com)
  • RUNX1 itself is the target of several chromosome rearrangements seen in leukemia. (nih.gov)
  • Our data demonstrate that RUNX1/ETO maintains leukemia by promoting cell cycle progression and identifies G1 CCND-CDK complexes as promising therapeutic targets for treatment of RUNX1/ETO-driven AML. (prinsesmaximacentrum.nl)
  • Recurring chromosomal translocations observed in human leukemia often result in the expression of fusion proteins that are DNA-binding transcription factors. (lincoln.ac.uk)
  • Gene translocations that repress the function of the Runx1 transcription factor play a critical role in the development of myeloid leukemia. (monocyte.eu)
  • RUNX1-positive leukemia cells in preclinical models. (lu.se)
  • RUNX1 was found to be rearranged in the leukemic cell DNAs from t(8;21)(q22;q22) AML patients. (wikipedia.org)
  • This strategy identified Cyclin D2 (CCND2) as a crucial transmitter of RUNX1/ETO-driven leukemic propagation. (prinsesmaximacentrum.nl)
  • Their unique feature is their ability to bind DNA at sequences known as promoter or enhancer regions. (biolegend.com)
  • Once the transcription factor binds to an enhancer region, this can cause stimulation or repression of gene transcription. (biolegend.com)
  • Runx1 controlled expression by binding to multiple sites within the mouse c-fms gene, allowing interaction between promoter and downstream enhancer elements. (monocyte.eu)
  • Together, these proteins form one version of a complex known as core binding factor (CBF). (medlineplus.gov)
  • The transcription of RUNX1 is regulated by 2 enhancers (regulatory element 1 and regulatory element 2), and these tissue specific enhancers enable the binding of lymphoid or erythroid regulatory proteins, therefore the gene activity of RUNX1 is highly active in the haematopoietic system. (wikipedia.org)
  • ChIP-sequencing analysis, using antibodies recognising PRMT5, LMO2 and RUNX1, showed overlapping peaks in T-ALL, confirming a functional relationship between these proteins. (bham.ac.uk)
  • Here, we show that the 8th zinc finger motif of MDS1/EVI1 is an oligomerization domain involved not only in interaction of AME with itself but also in interactions with the parental proteins, RUNX1 and MDS1/EVI1, from which AME is generated. (lincoln.ac.uk)
  • A Meta-Narrative Review of RUNX1-RUNX1T1 and its Relativity to CBF Dis" by Duong Do, Alma Guerrero et al. (mdanderson.org)
  • To address this, we conducted a meta-narrative review of the number of articles that correspond to each sub-theme of the approach to AML in the context of RUNX1-RUNX1T1 fusion gene, including the utilization of treatments, its detail on correlation to CBF complex, how the research method was depicted, limitations, audience, technology, and treatment. (mdanderson.org)
  • Refer to the evidence section for information about the selection of appropriate samples for testing RUNX1 germline pathogenic variants. (eviq.org.au)
  • The RUNX1 cDNA vector (RUNX1-P2A-RFP) contains RFP downstream of RUNX1 separated by a P2A sequence. (lipexogen.com)
  • The runt domain of RUNX1 binds to the core consensus sequence TGTGGNNN (where NNN can represent either TTT or TCA). (wikipedia.org)
  • The consensus binding site for CBF has been identified to be a 7 bp sequence PyGPyGGTPy. (wikipedia.org)
  • Unlike sequence-specific transcription factors, epigenetic regulators do not necessarily bind DNA at consensus sequences, but still achieve reproducible target binding in a manner that is cell and maturation-type specific. (frontiersin.org)
  • Some have been shown to bind epigenetic regulators, and thus constitute attractive candidates to mediate epigenetic target specificity. (frontiersin.org)
  • DNA-hypermethylation occurred particularly in up-stream promoter regions, shore-regions of CpG islands, binding sites for PU.1, HOXA5 and RUNX1, and it was reflected in differential gene expression and variant transcripts of DNMT3A. (nih.gov)
  • As a transcription factor (TF), its DNA binding ability is encoded by the runt domain (residues 50 - 177), which is homologous to the p53 family. (wikipedia.org)
  • RUNX1 can bind DNA as a monomer, but its DNA binding affinity is enhanced by 10 fold if it heterodimerises with the core binding factor β (CBFβ), also via the runt domain. (wikipedia.org)
  • Patients with a high expression of RUNX1 and/or IFNGR2 (HH/H) in the IDH-mutant subtype showed poorer prognosis and significantly increased infiltration of M2 macrophages. (bjbms.org)
  • Runx1 expression was repressed in CSF-1 stimulated, proliferating bone marrow-derived macrophages (BMM) and significantly increased in quiescent, CSF-1 starved cells. (monocyte.eu)
  • The identification of dimethylated arginine RUNX1 indicates a possible regulatory function for PRMT5, which may be related to their interaction with the LMO2 complex. (bham.ac.uk)
  • Higher RUNX1 expression was found to correlate with decreased median overall survival and disease-free survival in The Cancer Genome Atlas (TCGA) data set of high grade serous ovarian cancer (HGSOC) patients. (techscience.com)
  • 1 Of note, both eliminate the provisional entity of AML with mutated RUNX1 in WHO 2017 due to lack of data to support this as a unique entity. (cap.org)
  • Here, we will discuss the current insights and ideas regarding mutant RUNX1 in the context of malignant transformation of iBMFs, taking SCN as the leading example. (molcells.org)
  • Besides, we also found that the expression levels of RUNX1 and IFNGR2 were significantly reduced, and their correlation was enhanced in the IDH-mutant subtype. (bjbms.org)
  • RUNX1 plays an indispensable role in definitive hematopoiesis and hematological malignancies and as an emerging therapeutic target in cardiovascular disease. (lipexogen.com)
  • ChIP-sequnce analyis (ChIP-seq) revealed that fewer AR-binding sites were present in the context of p53 inhibition, suggesting that wild-type p53 is required for stable binding of AR to certain chromatin regions. (oncotarget.com)
  • We found specific binding patterns involving different complex members, which regulate gene expression that is involved in T-cell function and development. (bham.ac.uk)
  • Subsequent results confirmed that RUNX1, as an independent prognostic factor for LGG, may target interferon-gamma receptor 2 (IFNGR2) to regulate glioma cell proliferation, invasion, and migration. (bjbms.org)
  • Chromatin immunoprecipitation followed by sequencing (ChIP-seq) and microarray expression analysis were used to show that RUNX1 binds approximately 9,000 target sites in erythroid cells and is primarily active in the undifferentiated state. (ox.ac.uk)
  • This SP population is a small proportion of the total population of cancer cells characterised with high expression of drug transporters, a unique feature of stem cells and thereby can be isolated through their efflux properties of DNA binding dyes. (techscience.com)
  • RUNX1/ETO cooperates with AP-1 to drive CCND2 expression. (prinsesmaximacentrum.nl)
  • RUNX1 cDNA expression vectors is also available upon request. (lipexogen.com)
  • The RAW264.7 and Mono-Mac-6, macrophage-like cell lines expressed low levels of Runx1 and both showed growth arrest and cell death with ectopic expression of Runx1. (monocyte.eu)
  • GFP reporter activation in HEK293FT cells co-transfected with RUNX1 -TAG-Puro reporter and human RUNX1. (lipexogen.com)
  • HEK293FT cells were transfected with RUNX1-TAG-Puro plasmid along with cDNA encoding human RUNX1 or an empty vector (pcDNA). (lipexogen.com)
  • There is significant clinical heterogeneity in patients with RUNX1-FPDMM. (eviq.org.au)