The PAX-SIX-EYA-DACH network modulates GATA-FOG function in fly hematopoiesis and human erythropoiesis
| Autor: | Rajkumar Baldeosingh, Curt I. Civin, Akhilesh Pandey, T. Michael Creed, Nancy Fossett, Christian Eberly, Caroline S. Schlee, Jevon Cutler, Tami J. Kingsbury, MinJung Kim |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Cell type
Nerve Tissue Proteins Biology GATA Transcription Factors 03 medical and health sciences Gene Knockout Techniques 0302 clinical medicine Cell Line Tumor Gene expression Animals Drosophila Proteins Humans Paired Box Transcription Factors Erythropoiesis Gene Regulatory Networks Molecular Biology 030304 developmental biology Homeodomain Proteins 0303 health sciences Nuclear Proteins Lamellocyte differentiation GATA1 Phenotype Cell biology Hematopoiesis Haematopoiesis Drosophila 030217 neurology & neurosurgery Function (biology) Developmental Biology Research Article |
| Zdroj: | Development |
| Popis: | The GATA and PAX-SIX-EYA-DACH (PSEDN) transcriptional networks are essential for proper development across taxa. Here we demonstrate novel PSEDN roles in vivo in Drosophila hematopoiesis and in human erythropoiesis in vitro. Using Drosophila genetics, we show that PSEDN members function with GATA to block lamellocyte differentiation and maintain the prohemocyte pool. Overexpression of human SIX1 stimulated erythroid differentiation of human erythroleukemia TF1 cells and primary hematopoietic stem-progenitor cells. Conversely, SIX1 knockout impaired erythropoiesis in both cell types. SIX1 stimulation of erythropoiesis required GATA1, as SIX1 overexpression failed to drive erythroid phenotypes and gene expression patterns in GATA1 knockout cells. SIX1 can associate with GATA1 and stimulate GATA1-mediated gene transcription, suggesting SIX1-GATA1 physical interactions contribute to the observed functional interactions. In addition, both fly and human SIX proteins regulated GATA protein levels. Collectively, our findings demonstrate that SIX proteins enhance GATA function at multiple levels and reveal evolutionarily conserved cooperation between the GATA and PSEDN networks that may regulate developmental processes beyond hematopoiesis. |
| Databáze: | OpenAIRE |
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