RUNX1 represses the erythroid gene expression program during megakaryocytic differentiation
| Autor: | Hubert Serve, Thomas Oellerich, Helge Hussong, Nicole Kohrs, Carol Stocking, Kira Behrens, Henning Urlaub, Stefanie Herkt, Julia Herglotz, Halvard Bonig, Bartosch Wojcik, Stephan Kolodziej, Jörn Lausen, Joachim Koch, Michael A. Rieger, Jasmin Corso, Ashok Kumar, Olga N. Kuvardina |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Hematopoiesis and Stem Cells
Cellular differentiation Immunology Kruppel-Like Transcription Factors KLF1 Antigens CD34 Biology Biochemistry Thrombopoiesis chemistry.chemical_compound hemic and lymphatic diseases Proto-Oncogene Proteins Basic Helix-Loop-Helix Transcription Factors Humans Erythropoiesis Erythroid Precursor Cells T-Cell Acute Lymphocytic Leukemia Protein 1 Megakaryocyte Progenitor Cells Regulation of gene expression GATA2 food and beverages Cell Differentiation Cell Biology Hematology RUNX1 chemistry Gene Expression Regulation FLI1 embryonic structures Core Binding Factor Alpha 2 Subunit Cancer research K562 Cells Megakaryocytes TAL1 |
| Zdroj: | Blood |
| Popis: | The activity of antagonizing transcription factors represents a mechanistic paradigm of bidirectional lineage-fate control during hematopoiesis. At the megakaryocytic/erythroid bifurcation, the cross-antagonism of krueppel-like factor 1 (KLF1) and friend leukemia integration 1 (FLI1) has such a decisive role. However, how this antagonism is resolved during lineage specification is poorly understood. We found that runt-related transcription factor 1 (RUNX1) inhibits erythroid differentiation of murine megakaryocytic/erythroid progenitors and primary human CD34(+) progenitor cells. We show that RUNX1 represses the erythroid gene expression program during megakaryocytic differentiation by epigenetic repression of the erythroid master regulator KLF1. RUNX1 binding to the KLF1 locus is increased during megakaryocytic differentiation and counterbalances the activating role of T-cell acute lymphocytic leukemia 1 (TAL1). We found that corepressor recruitment by RUNX1 contributes to a block of the KLF1-dependent erythroid gene expression program. Our data indicate that the repressive function of RUNX1 influences the balance between erythroid and megakaryocytic differentiation by shifting the balance between KLF1 and FLI1 in the direction of FLI1. Taken together, we show that RUNX1 is a key player within a network of transcription factors that represses the erythroid gene expression program. |
| Databáze: | OpenAIRE |
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