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 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.
journal_name
Proc Natl Acad Sci U S Aauthors
Sposi NM,Zon LI,Carè A,Valtieri M,Testa U,Gabbianelli M,Mariani G,Bottero L,Mather C,Orkin SHdoi
10.1073/pnas.89.14.6353keywords:
subject
Has Abstract,Author List Incompletepub_date
1992-07-15 00:00:00pages
6353-7issue
14eissn
0027-8424issn
1091-6490journal_volume
89pub_type
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