ArticleMolecular and cellular biology2010
Thrombocytopenia in mice lacking the carboxy-terminal regulatory domain of the Ets transcription factor Fli1.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- FLI1 and GATA1 governHaematologica · 2025Article
- Transcription factor genetics and biology in predisposition to bone marrow failure and hematological malignancy.Frontiers in oncology · 2023Review
- A novel Boolean network inference strategy to model early hematopoiesis aging.Computational and structural biotechnology journal · 2023Article
- Patients with Chromosome 11q Deletions Are Characterized by Inborn Errors of Immunity Involving both B and T Lymphocytes.Journal of clinical immunology · 2022Article
- Interplay between FLI-1 and the LDB1 complex in murine erythroleukemia cells and during megakaryopoiesis.iScience · 2021Article
- Identification of diterpenoid compounds that interfere with Fli-1 DNA binding to suppress leukemogenesis.Cell death & disease · 2019Article
- Macrothrombocytopenia and dense granule deficiency associated with FLI1 variants: ultrastructural and pathogenic features.Haematologica · 2017Article
- Article
- The contribution of mouse models to the understanding of constitutional thrombocytopenia.Haematologica · 2016Review
- NF-E2, FLI1 and RUNX1 collaborate at areas of dynamic chromatin to activate transcription in mature mouse megakaryocytes.Scientific reports · 2016Article
- Large-scale production of megakaryocytes from human pluripotent stem cells by chemically defined forward programming.Nature communications · 2016Article
- Review
- SCL/TAL1-mediated transcriptional network enhances megakaryocytic specification of human embryonic stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- The transcription factor Fli-1 regulates monocyte, macrophage and dendritic cell development in mice.Immunology · 2013Article
- Understanding the role of ETS-mediated gene regulation in complex biological processes.Advances in cancer research · 2013Review
- Mouse models of diseases of megakaryocyte and platelet homeostasis.Mammalian genome : official journal of the International Mammalian Genome Society · 2011Review
- Multiple ETS family proteins regulate PF4 gene expression by binding to the same ETS binding site.PloS one · 2011Article
- Hierarchical differentiation of myeloid progenitors is encoded in the transcription factor network.PloS one · 2011Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Targeted disruption of the Fli1 gene results in embryonic lethality. To dissect the roles of functional domains in Fli1, we recently generated mutant Fli1 mice that express a truncated Fli1 protein (Fli1(ΔCTA)) that lacks the carboxy-terminal regulatory (CTA) domain. Heterozygous Fli1(ΔCTA) mice are viable, while homozygous mice have reduced viability. Early postnatal lethality accounts for 30% survival of homozygotes to adulthood. The peripheral blood of these viable Fli1(ΔCTA)/Fli1(ΔCTA) homozygous mice has reduced platelet numbers. Platelet aggregation and activation were also impaired and bleeding times significantly prolonged in these mutant mice. Analysis of mRNA from total bone marrow and purified megakaryocytes from Fli1(ΔCTA)/Fli1(ΔCTA) mice revealed downregulation of genes associated with megakaroyctic development, including c-mpl, gpIIb, gpIV, gpIX, PF4, NF-E2, MafG, and Rab27B. While Fli1 and GATA-1 synergistically regulate the expression of multiple megakaryocytic genes, the level of GATA-1 present on a subset of these promoters is reduced in vivo in the Fli1(ΔCTA)/Fli1(ΔCTA) mice, providing a possible mechanism for the impared transcription observed. Collectively, these data showed for the first time a hemostatic defect associated with the loss of a specific functional domain of the transcription factor Fli1 and suggest previously unknown in vivo roles in megakaryocytic cell differentiation.
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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.