ArticleMolecular and cellular biology2009
Differentiation-dependent interactions between RUNX-1 and FLI-1 during megakaryocyte development.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 78 citations in OpenAlex.
- Trial
- Megakaryocytes in myelofibrosis: mechanisms of fibrotic niche remodeling and therapeutic implications.Biomarker research · 2026Review
- Redox Regulation of Megakaryocyte Differentiation and Platelet Biogenesis.Antioxidants (Basel, Switzerland) · 2026Review
- FLI1 and GATA1 governHaematologica · 2025Article
- Dual mechanism of inflammation sensing by the hematopoietic progenitor genome.Science advances · 2025Article
- GATA1 in Normal and Pathologic Megakaryopoiesis and Platelet Development.Advances in experimental medicine and biology · 2024Review
- Article
- Current insights into the role of Fli-1 in hematopoiesis and malignant transformation.Cellular and molecular life sciences : CMLS · 2022Review
- Apoptosis in megakaryocytes: Safeguard and threat for thrombopoiesis.Frontiers in immunology · 2022Review
- The genome-wide impact of trisomy 21 on DNA methylation and its implications for hematopoiesis.Nature communications · 2021Article
- RUNX1-ETO: Attacking the Epigenome for Genomic Instable Leukemia.International journal of molecular sciences · 2019Review
- TCF-1 and HEB cooperate to establish the epigenetic and transcription profiles of CD4Nature immunology · 2018Article
- Targeting the CALR interactome in myeloproliferative neoplasms.JCI insight · 2018Article
- Genome wide mapping of ETV6 binding sites in pre-B leukemic cells.Scientific reports · 2018Article
- Comparative structure analysis of the ETSi domain of ERG3 and its complex with the E74 promoter DNA sequence.Acta crystallographica. Section F, Structural biology communications · 2018Article
- Article
- A Forward Genetic Screen Targeting the Endothelium Reveals a Regulatory Role for the Lipid Kinase Pi4ka in Myelo- and Erythropoiesis.Cell reports · 2018Article
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Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
The transcription factor RUNX-1 plays a key role in megakaryocyte differentiation and is mutated in cases of myelodysplastic syndrome and leukemia. In this study, we purified RUNX-1-containing multiprotein complexes from phorbol ester-induced L8057 murine megakaryoblastic cells and identified the ets transcription factor FLI-1 as a novel in vivo-associated factor. The interaction occurs via direct protein-protein interactions and results in synergistic transcriptional activation of the c-mpl promoter. Interestingly, the interaction fails to occur in uninduced cells. Gel filtration chromatography confirms the differentiation-dependent binding and shows that it correlates with the assembly of a complex also containing the key megakaryocyte transcription factors GATA-1 and Friend of GATA-1 (FOG-1). Phosphorylation analysis of FLI-1 with uninduced versus induced L8057 cells suggests the loss of phosphorylation at serine 10 in the induced state. Substitution of Ser10 with the phosphorylation mimic aspartic acid selectively impairs RUNX-1 binding, abrogates transcriptional synergy with RUNX-1, and dominantly inhibits primary fetal liver megakaryocyte differentiation in vitro. Conversely, substitution with alanine, which blocks phosphorylation, augments differentiation of primary megakaryocytes. We propose that dephosphorylation of FLI-1 is a key event in the transcriptional regulation of megakaryocyte maturation. These findings have implications for other cell types where interactions between runx and ets family proteins occur.
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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.