Cell cycle-dependent initiation and lineage-dependent abrogation of GATA-1 expression in pure differentiating hematopoietic progenitors.

Abstract

The programmed activation/repression of transcription factors in early hematopoietic differentiation has not yet been explored. The DNA-binding protein GATA-1 is required for normal erythroid development and regulates erythroid-expressed genes in maturing erythroblasts. We analyzed GATA-1 expression in early human adult hematopoiesis by using an in vitro system in which "pure" early hematopoietic progenitors are induced to gradual and synchronized differentiation selectively along the erythroid or granulocytemacrophage pathway by differential treatment with hematopoietic growth factors. The GATA-1 gene, though virtually silent in quiescent progenitors, is activated after entrance into the cell cycle upon stimulation with hematopoietic growth factors. Subsequently, increasing expression along the erythroid pathway contrasts with an abrupt downregulation in the granulocyte-macrophage lineage. These -results suggest a microenvironment-directed, two-step model for GATA-1 expression in differentiating hematopoietic progenitors that involves (7) cycle-dependent initiation and (ii) lineage-dependent maintenance or suppression. Hypothetically, on/off switches of lineage-restricted transactivators may underlie the binary fate decisions of hematopoietic progenitors.

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.…”

Apoptotic mechanisms in the control of erythropoiesis

“…GATA-1 is scarcely expressed in quiescent erythroid progenitors, but is rapidly induced when these cells are induced to erythroid differentiation by Epo and then progressively accumulates during erythroid maturation, being abundantly expressed during all stages of erythroid maturation. 6,7 The highest levels of GATA-1 are observed in CFU-Es and proerythroblasts. 8 The hemopoietic phenotype of GATA-1 knockout mice showed severe anemia with the production of an erythroid progeny, resulting in a maturational arrest at the level of proerythroblasts.…”

C-fms expression correlates with monocytic differentiation in PML-RARα+ acute promyelocytic leukemia

“…32 The normalized RNA was reverse transcribed according to the manufacturer's instructions (GIBCO-BRL, Gaithersburg, MD, USA). The RT-PCR was normalized for ␤2-microglobulin 32 (amplification within the linear range was achieved by 20 PCR cycles: denaturation at 95°C for 30 s, annealing at 54°C for 30 s, and extension at 72°C for 45 s).…”