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.

Potentiation of GATA-2 Activity through Interactions with the Promyelocytic Leukemia Protein (PML) and the t(15;17)-Generated PML-Retinoic Acid Receptor α Oncoprotein

“…Note that PML expression affected neither the expression level of GATA-2 nor GATA-2 binding to DNA. PML-RAR␣ oncoprotein may have the potential to associate with GATA-2, which is the predominant GATA factor expressed in early myeloid progenitor cells (44,45,47) representing the cellular target for transformation in APL.…”

“…Recently, GATA-2 has been shown to play roles in regulating proliferation of hematopoietic cells, with overexpressed GATA-2 having the ability to inhibit the cell cycle (27,53). Since GATA-2 is a predominant GATA factor expressed in early myeloid cells (44,47,48), PML may have a functional link with GATA-2 in terms of proliferation and differentiation in myeloid lineages.…”

“…Surprisingly, evidence linking GATA family members with leukemic transformation has been generally lacking. GATA-2 is often expressed in leukemia cells and cell lines (44,47), but this may simply reflect the progenitor status (and hence GATA-2 positivity) of the target cell in transformation, rather than any leukemogenic effect of GATA-2 itself. Our results raise the possibility that a component of PML-RAR␣'s leukemic potential is realized via GATA-2.…”

“…Much attention has focused on how these different factors, which seemingly bind to similar (or identical) cis elements, carry out their distinct biological functions. Part of the answer may be attributed to their different expression profiles: GATA-1 is expressed at a high level in erythroid cells, mast cells, megakaryocytes, and eosinophils and at a low level in multipotential progenitors (18,40,62,81), whereas GATA-2 is more broadly expressed among hematopoietic cells, with particularly prominent expression in early progenitors, as well as megakaryocytes and mast cells (45,47,48). GATA-3 expression within hematopoiesis is confined to T lymphocytes (33,48).…”

LYL1 facilitates AETFC assembly and gene activation by recruiting CARM1 in t(8;21) AML

“…In addition, in exploring the possibility that other TFs are involved in AETFC function, motif enrichment analyses of AETFC- and AEC-bound genomic sites have shown that the GATA2 motif sequence is specifically enriched at AETFC peaks relative to AEC peaks. GATA2, which is a member of the GATA family of zinc finger–containing TFs ( 48 ), has been identified as a critical regulator of hematopoietic stem cells (HSCs) during oncogenesis in the hematopoietic system. In this regard, deletion of GATA2 in Meis1a/Hoxa9-driven AML impedes maintenance and self-renewal of leukemic stem cells (LSCs) ( 49 ).…”