The PAX-SIX-EYA-DACH network modulates GATA-FOG function in fly hematopoiesis and human erythropoiesis.

Autor:	Creed TM; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Baldeosingh R; Center for Vascular and Inflammatory Diseases University of Maryland School of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.; Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.; Manipal Academy of Higher Education (MAHE), Manipal 576104, Karnataka, India., Eberly CL; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Schlee CS; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Kim M; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Cutler JA; McKusick-Nathans Institute of Genetic Medicine, Departments of Biological Chemistry, Oncology and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Pandey A; McKusick-Nathans Institute of Genetic Medicine, Departments of Biological Chemistry, Oncology and Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA., Civin CI; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.; Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Fossett NG; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA tkingsbury@som.umaryland.edu nfossett@gmail.com.; Center for Vascular and Inflammatory Diseases University of Maryland School of Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.; Department of Pathology, University of Maryland School of Medicine, Baltimore, MD 21201, USA., Kingsbury TJ; Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA tkingsbury@som.umaryland.edu nfossett@gmail.com.; Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA.; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Jazyk:	angličtina
Zdroj:	Development (Cambridge, England) [Development] 2020 Jan 03; Vol. 147 (1). Date of Electronic Publication: 2020 Jan 03.
DOI:	10.1242/dev.177022
Abstrakt:	The GATA and PAX-SIX-EYA-DACH transcriptional networks (PSEDNs) 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 that 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. Competing Interests: Competing interestsThe authors declare no competing or financial interests. (© 2020. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu