Differential Contribution of the Gata1 Gene Hematopoietic Enhancer to Erythroid Differentiation
- 1 March 2009
- journal article
- Published by Informa UK Limited in Molecular and Cellular Biology
- Vol. 29 (5), 1163-1175
- https://doi.org/10.1128/mcb.01572-08
Abstract
GATA1 is a key regulator of erythroid cell differentiation. To examine how Gata1 gene expression is regulated in a stage-specific manner, transgenic mouse lines expressing green fluorescent protein (GFP) reporter from the Gata1 locus in a bacterial artificial chromosome (G1BAC-GFP) were prepared. We found that the GFP reporter expression faithfully recapitulated Gata1 gene expression. Using GFP fluorescence in combination with hematopoietic surface markers, we established a purification protocol for two erythroid progenitor fractions, referred to as burst-forming units-erythroid cell-related erythroid progenitor (BREP) and CFU-erythroid cell-related erythroid progenitor (CREP) fractions. We examined the functions of the Gata1 gene hematopoietic enhancer (G1HE) and the highly conserved GATA box in the enhancer core. Both deletion of the G1HE and substitution mutation of the GATA box caused almost complete loss of GFP expression in the BREP fraction, but the CREP stage expression was suppressed only partially, indicating the critical contribution of the GATA box to the BREP stage expression of Gata1. Consistently, targeted deletion of G1HE from the chromosomal Gata1 locus provoked suppressed expression of the Gata1 gene in the BREP fraction, which led to aberrant accumulation of BREP stage hematopoietic progenitor cells. These results demonstrate the physiological significance of the dynamic regulation of Gata1 gene expression in a differentiation stage-specific manner.Keywords
This publication has 56 references indexed in Scilit:
- Ablation of Gata1 in adult mice results in aplastic crisis, revealing its essential role in steady-state and stress erythropoiesisBlood, 2008
- Treating AML with ATRA? Beware MN1!Blood, 2007
- Regulation of GATA1 Gene ExpressionThe Journal of Biochemistry, 2007
- Real-time monitoring of stress erythropoiesis in vivo using Gata1 and β-globin LCR luciferase transgenic miceBlood, 2006
- Abnormalities of GATA-1 in Megakaryocytes from Patients with Idiopathic MyelofibrosisThe American Journal of Pathology, 2005
- Graded Levels of GATA-1 Expression Modulate Survival, Proliferation, and Differentiation of Erythroid ProgenitorsJournal of Biological Chemistry, 2005
- Multiple, Distant Gata2 Enhancers Specify Temporally and Tissue-Specific Patterning in the Developing Urogenital SystemMolecular and Cellular Biology, 2004
- Leukemogenesis Caused by Incapacitated GATA-1 FunctionMolecular and Cellular Biology, 2004
- Frequent mutations in the GATA-1 gene in the transient myeloproliferative disorder of Down syndromeBlood, 2003
- Locus control regions of mammalian β-globin gene clusters: combining phylogenetic analyses and experimental results to gain functional insightsGene, 1997