Transcription factor GATA-2 is expressed in erythroid, early myeloid, and CD34+ human leukemia-derived cell lines

Abstract

To understand the functional roles that the GATA factors may play during hematopoietic cell differentiation, we examined the expression of GATA factor mRNAs and protein products in various human cell lines. Blot hybridization analyses demonstrated that GATA-1 and GATA-2 mRNAs are expressed abundantly in a set of cell lines established from human myelogenous leukemia cells, but the expression pattern of each factor is distinct. GATA-2 mRNA is expressed in all cell lines tested that express erythroid markers, and, in addition, the mRNA is also expressed in three CD34+ cell lines and two early myeloid cell lines. In contrast, the expression of GATA-1 mRNA showed tight correlation to that of the erythroid/megakaryocytic lineage markers. We also found that the GATA-2 probe identifies two types of mRNA. Structural analysis of genomic DNA clones encoding human GATA-2 coupled with RNA blot analysis demonstrated that there exists an alternative use of polyadenylation consensus sequences in a single exon and this causes the molecular heterogeneity among GATA-2 mRNAs. Through immunochemical and immunohistochemical analyses using anti-GATA-1- and anti-GATA-2- specific antibodies, GATA-2 protein was clearly shown to be present in the nuclei of leukemia-derived early myeloid and CD34+ cell lines, whereas both GATA-1 and GATA-2 proteins are expressed in erythroid/megakaryocytic cell lines. Thus, the expression profile of GATA-2 is consistent with the hypothesis that GATA-2 plays unique roles for the transcriptional activation of genes in cells at an early stage of hematopoietic differentiation and in developing cells of the erythroid and myeloid lineages.

Differential roles of GATA‐1 and GATA‐2 in growth and differentiation of mast cells

“…The expression profile of GATA-2 originally suggested that this factor contributes to the transcriptional activation of a group of genes specifically expressed in early stage haematopoietic progenitor cells (Leonard et al 1993a;Nagai et al 1994). GATA-2 mRNA was also found in cells differentiating along the erythroid, megakaryocytic and mast cell lineage pathways (Yamamoto et al 1990;Zon et al 1991;Dorfman et al 1992).…”

“…To perform RNA blot hybridization analysis, we first isolated cDNA clones encoding mouse GATA-2. We screened a foetal mouse liver cDNA library using a partial human GATA-2 cDNA clone (Nagai et al 1994). One clone (pmG2a) bearing the entire coding region of mGATA-2 was isolated (data not shown; DDBJ/GENBANK/EMBL accession number: AB000096), and this clone was used for RNA blot analysis.…”

“…For example, GATA-1 mRNA is found in erythroid cells, megakaryocytes, eosinophils and mast cells in haematopoietic lineages (Romeo et al 1990;Martin et al 1990;Leonard et al 1993a;Zon et al 1993) and in Sertoli cells of the testis (Ito et al 1993;Yomogida et al 1994). GATA-2 mRNA is also expressed in the same haematopoietic lineages (Zon et al 1991;Dorfman et al 1992), and is, in addition, found in both normal and leukaemic CD34 þ human cells, suggesting that GATA-2 may play an earlier role than GATA-1 in haematopoietic differentiation (Leonard et al 1993a;Nagai et al 1994). Analysis of GATA-1-null ES cells that were generated by targeted mutagenesis showed that the mutant cells do not contribute to the mature erythroid population in chimeric animals (Pevny et al 1991).…”

GATA transcription factors are involved in IgE‐dependent mast cell degranulation by enhancing the expression of phospholipase C‐γ1

“…Although the precise roles of GATA1 on mast cell development have not been fully elucidated, previous studies showed that the reduced expression of GATA1 by targeted disruption of an upstream enhancer results in the formation of abnormal progenitors that differentiate into erythroid cells, megakaryocytes and mast cells (Migliaccio et al 2003;Ghinassi et al 2007). GATA2 is expressed in hematopoietic stem cells and multilineage progenitors and plays key roles in the maintenance and proliferation of those cells (Nagai et al 1994;Minegishi et al 1998Minegishi et al , 1999. Although the early embryonic lethality observed in Gata2 null mice (Tsai et al 1994) has precluded studies of Gata2 deficiency in mast cells in vivo, in vitro differentiation studies of embryonic stem (ES) cells have demonstrated that GATA2-deficient ES cells lose the ability to differentiate into mast cells (Tsai & Orkin 1997).…”

Important roles of reversible acetylation in the function of hematopoietic transcription factors

“…GATA-2 is abundantly expressed in immature erythroid progenitors and declines over the course of maturation. It is also found in other cell types [32,33]. Studies on GATA-2 deficient mice have shown that it plays an important role during the early stages of erythropoiesis.…”