ArticleThe Journal of biological chemistry2014
Runx1 regulation of Pu.1 corepressor/coactivator exchange identifies specific molecular targets for leukemia differentiation therapy.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Differentiation therapy and the mechanisms that terminate cancer cell proliferation without harming normal cells.Cell death & disease · 2018Pooled it
- A pilot clinical trial of oral tetrahydrouridine/decitabine for noncytotoxic epigenetic therapy of chemoresistant lymphoid malignancies.Seminars in hematology · 2021Trial
- Evaluation of noncytotoxic DNMT1-depleting therapy in patients with myelodysplastic syndromes.The Journal of clinical investigation · 2015Trial
- Review
- FLT3-ITD signals for CEBPA and p53 proteolysis by the ubiquitin-proteosome pathway.Research square · 2026Article
- FLT3-ITD signals for CEBPA and p53 proteolysis by the ubiquitin-proteosome pathway.bioRxiv : the preprint server for biology · 2026Article
- DNA methyltransferase inhibitors in hematological malignancies and solid tumors.International journal of cancer · 2026Review
- Combining drugs that bypass p53 to treat TP53-mutated leukemias.Blood advances · 2025Article
- Neuroendocrine lineage commitment of small cell lung cancers can be leveraged into p53-independent non-cytotoxic therapy.Cell reports · 2023Article
- Changing paradigms in oncology: Toward noncytotoxic treatments for advanced gliomas.International journal of cancer · 2022Review
- PU.1-Dependent Enhancer Inhibition Separates Tet2-Deficient Hematopoiesis from Malignant Transformation.Blood cancer discovery · 2022Article
- HDAC1 and PRC2 mediate combinatorial control in SPI1/PU.1-dependent gene repression in murine erythroleukaemia.Nucleic acids research · 2022Article
- Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors.International journal of molecular sciences · 2022Review
- BCL11A promotes myeloid leukemogenesis by repressing PU.1 target genes.Blood advances · 2022Article
- PBRM1 loss in kidney cancer unbalances the proximal tubule master transcription factor hub to repress proximal tubule differentiation.Cell reports · 2021Article
- The Genome-Wide Binding Profile for Human RE1 Silencing Transcription Factor Unveils a Unique Genetic Circuitry in Hippocampus.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Decitabine- and 5-azacytidine resistance emerges from adaptive responses of the pyrimidine metabolism network.Leukemia · 2021Article
- The RUNX1/RUNX1T1 network: translating insights into therapeutic options.Experimental hematology · 2021Review
- Epigenetic modifier directed therapeutics to unleash healthy genes in unhealthy cells.Seminars in hematology · 2021Article
- Extended experience with a non-cytotoxic DNMT1-targeting regimen of decitabine to treat myeloid malignancies.British journal of haematology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Gene activation requires cooperative assembly of multiprotein transcription factor-coregulator complexes. Disruption to cooperative assemblage could underlie repression of tumor suppressor genes in leukemia cells. Mechanisms of cooperation and its disruption were therefore examined for PU.1 and RUNX1, transcription factors that cooperate to activate hematopoietic differentiation genes. PU.1 is highly expressed in leukemia cells, whereas RUNX1 is frequently inactivated by mutation or translocation. Thus, coregulator interactions of Pu.1 were examined by immunoprecipitation coupled with tandem mass spectrometry/Western blot in wild-type and Runx1-deficient hematopoietic cells. In wild-type cells, the NuAT and Baf families of coactivators coimmunoprecipitated with Pu.1. Runx1 deficiency produced a striking switch to Pu.1 interaction with the Dnmt1, Sin3A, Nurd, CoRest, and B-Wich corepressor families. Corepressors of the Polycomb family, which are frequently inactivated by mutation or deletion in myeloid leukemia, did not interact with Pu.1. The most significant gene ontology association of Runx1-Pu.1 co-bound genes was with macrophages, therefore, functional consequences of altered corepressor/coactivator exchange were examined at Mcsfr, a key macrophage differentiation gene. In chromatin immunoprecipitation analyses, high level Pu.1 binding to the Mcsfr promoter was not decreased by Runx1 deficiency. However, the Pu.1-driven shift from histone repression to activation marks at this locus, and terminal macrophage differentiation, were substantially diminished. DNMT1 inhibition, but not Polycomb inhibition, in RUNX1-translocated leukemia cells induced terminal differentiation. Thus, RUNX1 and PU.1 cooperate to exchange corepressors for coactivators, and the specific corepressors recruited to PU.1 as a consequence of RUNX1 deficiency could be rational targets for leukemia differentiation therapy.
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Registered trials
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