Megakaryocytic and erythrocytic lineages share specific transcription factors

Abstract

Erythroid-specific genes contain binding sites for NF-E1 (also called GF-1 and Eryf-1; refs 1-3 respectively), the principal DNA-binding protein of the erythrocytic lineage. NF-E1 expression seems to be restricted to the erythrocytic lineage. A closely related (if not identical) protein is found in both a human megakaryocytic cell line and purified human megakaryocytes; it binds to promoter regions of two megakaryocytic-specific genes. The binding sites and partial proteolysis profile of this protein are indistinguishable from those of the erythroid protein; also, NF-E1 messenger RNA is the same size in both the megakaryocytic and erythroid cell lines. Furthermore, point mutations that abolish binding of NF-E1 result in a 70% decrease in the transcriptional activity of a megakaryocytic-specific promoter. We also find that NF-E2, another trans-acting factor of the erythrocytic lineage, is present in megakaryocytes. Transcriptional effects in both lineages might then be mediated in part by the same specific trans-acting factors. Our data strengthen the idea of a close association between the erythrocytic and the megakaryocytic lineages and could also explain the expression of markers specific to the erythrocytic and megakaryocytic lineages in most erythroblastic and megakaryoblastic permanent cell lines.

Transforming Acidic Coiled-coil Protein 3 (TACC3) Controls Friend of GATA-1 (FOG-1) Subcellular Localization and Regulates the Association between GATA-1 and FOG-1 during Hematopoiesis

“…1). GATA-1 is expressed in erythroid, megakaryocytic, mast, and eosinophilic cells and at lower levels in multipotential progenitors (2)(3)(4)(5). Consistent with this limited cellular distribution, GATA-1 is required for proper maturation of all four lineages (erythroid, megakaryocyte, mast, and eosinophil) in which it is normally expressed.…”

Alternative Promoters Regulate Transcription of the Mouse GATA-2 Gene

“…Our preliminary data show that the reporter gene expression in the hematopoietic stem cell fraction of bone marrow cells and in aorta/gonad/mesonephros region of mouse embryo is mainly driven by IS promoter. 5 The basic transcriptional activity of the IS promoter was found to be localized within the proximal 80 bp. Specific transcription factor interactions to the Ϫ85 to Ϫ50 region of the IS promoter were identified through DNase I footprinting analysis and EMSA using nuclear extracts from P815 cells.…”

“…Thereafter, however, GATA-2-positive cells are only rarely detected in various mouse tissues, suggesting that the level of GATA-2 mRNA is high when hematopoietic progenitors are rapidly expanding. 5 An assessment of the trans-activation activity in a transgenic mouse system, using constructs containing both the mGATA-2 promoter driving the expression of the Escherichia coli ␤-galactosidase gene, is now ongoing in this laboratory. Our preliminary data show that the reporter gene expression in the hematopoietic stem cell fraction of bone marrow cells and in aorta/gonad/mesonephros region of mouse embryo is mainly driven by IS promoter.…”

GATA-1 regulates the generation and function of basophils

“…Each GATA factor shows a tissue-and cell-restricted pattern of expression. GATA-1 is expressed in erythroid cells, megakaryocytes, mast cells, and eosinophils among hematopoietic lineages (5)(6)(7)(8)(9), and in Sertoli cells of the testis (10). The critical role for GATA-1 in erythropoiesis has been clearly illustrated by establishing GATA-1−null mice that die during embryogenesis due to severe anemia (11).…”