Eosinophil granule major basic protein (MBP) is expressed exclusively in eosinophils and basophils in hematopoietic cells. In our previous study, we demonstrated a major positive regulatory role for GATA-1 and a negative regulatory role for GATA-2 in MBP gene transcription. Further analysis of the MBP promoter region identified a C/EBP (CCAAT/enhancer-binding protein) consensus binding site 6 b...

GATA-1 and PU.1 are essential hematopoietic transcription factors that control erythromegakaryocytic and myelolymphoid differentiation, respectively. These proteins antagonize each other through direct physical interaction to repress alternate lineage programs. We used immortalized Gata1(-) erythromegakaryocytic progenitor cells to study how PU.1/Sfpi1 expression is regulated by GATA-1 and GATA...

GATA-1 controls hematopoietic development by activating and repressing gene transcription, yet the in vivo mechanisms that specify these opposite activities are unknown. By examining the composition of GATA-1-associated protein complexes in a conditional erythroid rescue system as well as through the use of tiling arrays we detected the SCL/TAL1, LMO2, Ldb1, E2A complex at all positively acting...

The multicomponent neuron-specific enhancer of the gonadotropin-releasing hormone (GnRH) gene specifically targets expression to the GnRH-secreting neurons of the hypothalamus, a small population of specialized cells which play a central role in regulating reproductive function. Utilizing the GnRH-secreting hypothalamic neuronal cell line, GT1, as a model system, we show that members of the GAT...

Gene targeting studies have demonstrated that the zinc finger transcription factor GATA-6 lies upstream in a transcriptional cascade that controls differentiation of the visceral endoderm. To understand the function of GATA-6 in the visceral endoderm and to identify genes regulated by GATA-6 in this tissue, subtractive hybridization was performed using template cDNAs derived from differentiated...

GATA-1 is essential for the development of erythroid and megakaryocytic lineages. We found that GATA-1 gene knockdown female (GATA-1.05/X) mice frequently develop a hematopoietic disorder resembling myelodysplastic syndrome that is characterized by the accumulation of progenitors expressing low levels of GATA-1. In this study, we demonstrate that GATA-1.05/X mice suffer from two distinct types ...

Mast cells are pivotal effector cells in IgE-mediated allergic reactions. GATA transcriptional factors such as GATA-1 and GATA-2 are expressed in mast cells, and recent studies have revealed that both GATA-1 and GATA-2 are required for mast cell development. However, the role of GATA transcriptional factors in differentiated mast cells has remained largely unknown. In this study, we repressed t...

Gene-targeting experiments in transgenic mice have revealed an essential role for GATA-1 in the normal differentiation and development of erythroid cells. GATA-1 is phosphorylated in vivo on seven of its serine residues; the regulation and function of GATA-1 phosphorylation, however, is not understood. Here we demonstrate a role for MAP kinase (MAPK) signalling in the control of GATA-1 phosphor...

We previously reported that IL-3 signaling induces phosphorylation of GATA-1 at the serine²⁶ position, which contributes to IL-3-mediated anti-apoptotic response. Here, we demonstrate that phosphorylation of GATA-1 at serine²⁶ is also transiently induced in cells of the erythroid lineage (primary erythroblasts and erythrocyte-committed progenitors [EPs]) by erythropoietin (EPO), the principal c...

GATA-3 expression is crucial for T cell development and peaks during commitment to the T cell lineage, midway through the CD4(-)CD8(-) (double-negative [DN]) stages 1-3. We used RNA interference and conditional deletion to reduce GATA-3 protein acutely at specific points during T cell differentiation in vitro. Even moderate GATA-3 reduction killed DN1 cells, delayed progression to the DN2 stage...