ArticleBlood2012
Runx1 deletion or dominant inhibition reduces Cebpa transcription via conserved promoter and distal enhancer sites to favor monopoiesis over granulopoiesis.
Article in Blood, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 97 citations in OpenAlex.
- Engineering IL-4 resistant proinflammatory human myeloid cells for cancer immunotherapy.Molecular oncology · 2026Article
- Impact of RUNX1 mutations at distinct sites on the clinical characteristics and prognosis of patients with acute myeloid leukemia.BMC cancer · 2026Article
- A review of C/EBP α: a potential novel target for solid tumor intervention.Journal of translational medicine · 2025Review
- C/EBPα activatesScience immunology · 2025Article
- A system-level model reveals that transcriptional stochasticity is required for hematopoietic stem cell differentiation.NPJ systems biology and applications · 2024Article
- Cebpa is required for haematopoietic stem and progenitor cell generation and maintenance in zebrafish.Open biology · 2024Article
- Pharmacological inhibition of RUNX1 reduces infarct size after acute myocardial infarction in rats and underlying mechanism revealed by proteomics implicates repressed cathepsin levels.Functional & integrative genomics · 2024Article
- The contributions of DNA accessibility and transcription factor occupancy to enhancer activity during cellular differentiation.G3 (Bethesda, Md.) · 2024Article
- Comprehensive summary: the role of PBX1 in development and cancers.Frontiers in cell and developmental biology · 2024Review
- From Genotype to Phenotype: How Enhancers Control Gene Expression and Cell Identity in Hematopoiesis.HemaSphere · 2023Review
- RUN(X) out of blood: emerging RUNX1 functions beyond hematopoiesis and links to Down syndrome.Human genomics · 2023Review
- RUNX1::ETO translocations must precede CSF3R mutations to promote acute myeloid leukemia development.Leukemia · 2023Article
- RUNX1 isoform disequilibrium promotes the development of trisomy 21-associated myeloid leukemia.Blood · 2023Article
- Identification of the global miR-130a targetome reveals a role for TBL1XR1 in hematopoietic stem cell self-renewal and t(8;21) AML.Cell reports · 2022Article
- Hematopoietic Stem Cell Factors: Their Functional Role in Self-Renewal and Clinical Aspects.Frontiers in cell and developmental biology · 2022Review
- Regulation of emergency granulopoiesis during infection.Frontiers in immunology · 2022Review
- The complex landscape of haematopoietic lineage commitments is encoded in the coarse-grained endogenous network.Royal Society open science · 2021Article
- Myeloid lncRNA LOUP mediates opposing regulatory effects of RUNX1 and RUNX1-ETO in t(8;21) AML.Blood · 2021Article
- Chronic interleukin-1 exposure triggers selection for Cebpa-knockout multipotent hematopoietic progenitors.The Journal of experimental medicine · 2021Article
- Emerging therapies for inv(16) AML.Blood · 2021Review
4 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Deletion of Runx1 in adult mice produces a myeloproliferative phenotype. We now find that Runx1 gene deletion increases marrow monocyte while reducing granulocyte progenitors and that exogenous RUNX1 rescues granulopoiesis. Deletion of Runx1 reduces Cebpa mRNA in lineage-negative marrow cells and in granulocyte-monocyte progenitors or common myeloid progenitors. Pu.1 mRNA is also decreased, but to a lesser extent. We also transduced marrow with dominant-inhibitory RUNX1a. As with Runx1 gene deletion, RUNX1a expands lineage-Sca-1+c-kit+ and myeloid cells, increased monocyte CFUs relative to granulocyte CFUs, and reduced Cebpa mRNA. Runx1 binds a conserved site in the Cebpa promoter and binds 4 sites in a conserved 450-bp region located at +37 kb; mutation of the enhancer sites reduces activity 6-fold in 32Dcl3 myeloid cells. Endogenous Runx1 binds the promoter and putative +37 kb enhancer as assessed by ChIP, and RUNX1-ER rapidly induces Cebpa mRNA in these cells, even in cycloheximide, consistent with direct gene regulation. The +37 kb region contains strong H3K4me1 histone modification and p300-binding, as often seen with enhancers. Finally, exogenous C/EBPα increases granulocyte relative to monocyte progenitors in Runx1-deleted marrow cells. Diminished CEBPA transcription and consequent impairment of myeloid differentiation may contribute to leukemic transformation in acute myeloid leukemia cases associated with decreased RUNX1 activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.