ERYTHROPOIETIN STIMULATES TRANSCRIPTION OF THE TAL1 SCL GENE AND PHOSPHORYLATION OF ITS PROTEIN PRODUCTS/

Activation of the TAL1 (or SCL) gene, originally identified through it s involvement by a recurrent chromosomal translocation, is the most fr equent molecular lesion recognized in T-cell acute lymphoblastic leuke mia. The protein products of this gene contain the basic-helix-loop-he lix motif characteristic of a large family of transcription factors th at bind to the canonical DNA sequence CANNTG as protein heterodimers. TAL1 expression by erythroid cells in vivo and in chemical-induced ery throleukemia cell lines in vitro suggested the gene might regulate asp ects of erythroid differentiation. Since the terminal events of erythr opoiesis are controlled by the glycoprotein hormone erythropoietin (Ep o), we investigated whether the expression or activity of the TAL1 gen e and its protein products were affected by Epo in splenic erythroblas ts from mice infected with an anemia-inducing strain of Friend virus ( FVA cells), Epo elicited a rapid, dose-related increase in TALI mRNA b y increasing transcription of the gene and stabilizing one of its mRNA s, An Epo-inducible TAL1 DNA binding activity was identified in FVA ce ll nuclear extracts that subsequently decayed despite accumulating mRN A and protein. Induction of DNA binding activity was associated tempor ally with Epo-induced phosphorylation of nuclear TAL1 protein. These r esults indicate that Epo acts at both transcriptional and posttranscri ptional levels on the TAL1 locus in Friend virus-induced erythroblasts and establish a link between Epo signaling mechanisms and a member of a family of transcription factors involved in the differentiation of diverse cell lineages.