Cell Cycle-Dependent Initiation and Lineage-Dependent Abrogation of GATA-1 Expression in Pure Differentiating Hematopoietic Progenitors

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 89; no. 14; pp. 6353 - 6357
• Main Authors: Sposi, N. M., Zon, L. I., Care, A., Valtieri, M., Testa, U., Gabbianelli, M., Mariani, G., Bottero, L., Mather, C., Orkin, S. H., Peschle, C.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 15.07.1992; National Acad Sciences; National Academy of Sciences
• Subjects: Antigens, Surface - analysis; Base Sequence; Biological and medical sciences; Cell Cycle; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell growth; Cell lines; Cell physiology; Cells; Cellular biology; Cellular differentiation; Clone Cells; Cultured cells; Deoxyribonucleic acid; DNA; DNA-Binding Proteins - metabolism; Epics; Erythroid Precursor Cells - physiology; Erythroid progenitor cells; Erythroid-Specific DNA-Binding Factors; Fundamental and applied biological sciences. Psychology; GATA1 Transcription Factor; Gene Expression; Hematopoiesis; Hematopoietic Stem Cells - physiology; Humans; Liquids; Molecular and cellular biology; Molecular Sequence Data; Oligodeoxyribonucleotides - chemistry; Polymerase Chain Reaction; Progenitor cells; Proteins; RNA, Messenger - genetics; Stem cells; Transcription Factors - metabolism; Human; Regulation(control); Erythroid cell; Gene; Transcription; Hematopoiesis; Cell cycle; Transcription factor; Cell differentiation; Precursor; Growth factor
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.89.14.6353

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 granulocyte-macrophage 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 (i) 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.