Beta-Actin Is Involved in Modulating Erythropoiesis during Development by Fine-Tuning Gata2 Expression Levels |
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| Authors: | Davina Tondeleir Benjamin Drogat Karolina Slowicka Karima Bakkali Sonia Bartunkova Steven Goossens Jody J Haigh Christophe Ampe |
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| Institution: | 1. Department of Biochemistry, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.; 2. Vascular Cell Biology Unit, Department for Molecular Biomedical Research, VIB, Ghent, Belgium.; 3. Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium.; Baylor College of Medicine, United States of America, |
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| Abstract: | The functions of actin family members during development are poorly understood. To investigate the role of beta-actin in mammalian development, a beta-actin knockout mouse model was used. Homozygous beta-actin knockout mice are lethal at embryonic day (E)10.5. At E10.25 beta-actin knockout embryos are growth retarded and display a pale yolk sac and embryo proper that is suggestive of altered erythropoiesis. Here we report that lack of beta-actin resulted in a block of primitive and definitive hematopoietic development. Reduced levels of Gata2, were associated to this phenotype. Consistently, ChIP analysis revealed multiple binding sites for beta-actin in the Gata2 promoter. Gata2 mRNA levels were almost completely rescued by expression of an erythroid lineage restricted ROSA26-promotor based GATA2 transgene. As a result, erythroid differentiation was restored and the knockout embryos showed significant improvement in yolk sac and embryo vascularization. These results provide new molecular insights for a novel function of beta-actin in erythropoiesis by modulating the expression levels of Gata2 in vivo. |
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