Expression of tal-1 and GATA-binding proteins during human hematopoiesis

• Published in: Blood 1993-02, Vol.81 (3), p.647-655
• Main Authors: MOUTHON, M.-A, BERNARD, O, MITJAVILA, M.-T, ROMEO, P.-H, VAINCHENKER, W, MATHIEU-MAHUL, D
• Format: Article
• Language: English
• Subjects: Adult; Antigens, CD - analysis; Antigens, CD34; Base Sequence; Basic Helix-Loop-Helix Transcription Factors; Biological and medical sciences; Blood Platelets - physiology; Bone Marrow - physiology; Cell differentiation, maturation, development, hematopoiesis; Cell Line; Cell physiology; Child; DNA-Binding Proteins - genetics; Erythroid-Specific DNA-Binding Factors; Exons; Fundamental and applied biological sciences. Psychology; GATA1 Transcription Factor; Gene Rearrangement; Hematopoiesis - physiology; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Humans; Leukemia - blood; Leukemia - genetics; Leukemia-Lymphoma, Adult T-Cell - blood; Leukemia-Lymphoma, Adult T-Cell - genetics; Megakaryocytes - cytology; Megakaryocytes - physiology; Molecular and cellular biology; Molecular Sequence Data; Oligodeoxyribonucleotides; Polymerase Chain Reaction - methods; Promoter Regions, Genetic; Proto-Oncogene Proteins - genetics; RNA, Messenger - genetics; RNA, Messenger - metabolism; T-Cell Acute Lymphocytic Leukemia Protein 1; Thymus Gland - physiology; Transcription Factors - genetics; Tumor Cells, Cultured
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v81.3.647.647

Tal-1 rearrangements are associated with nearly 30% of human T acute lymphoblastic leukemia. Tal-1 gene encodes a putative transcription factor with a basic helix-loop-helix domain and is known to be predominantly expressed in hematopoietic cells. We investigated the pattern of tal-1 expression in purified human hematopoietic cells by in situ hybridization and reverse transcriptase polymerase chain reaction analysis. Both methods demonstrated that the tal-1 gene is expressed in megakaryocytes and erythroblasts as well as in basophilic granulocytes. In addition, our results indicate that the tal-1 1A promoter, which contains two consensus GATA-binding sites, is active mainly in these lineages. Because the GATA-1 gene is known to transactivate several genes specific for the erythroid, megakaryocytic, and mastocytic/basophilic lineages, we studied GATA-1 expression in these purified hematopoietic cells. We found that GATA-1 and tal-1 genes are coexpressed in these three lineages. Remarkably, the expression of both genes is downmodulated during erythroid and megakaryocytic terminal maturation. In immature hematopoietic cells, tal-1 and GATA-1 genes are coexpressed in committed progenitors cells (CD34+/CD38(2+)), whereas they are not detectable in the most primitive cells (CD34(2+)/CD38-). In contrast, GATA-2 is strongly expressed in both most primitive and committed progenitors cells, whereas GATA-3 is mostly detected in most primitive ones. Altogether our results strongly suggest that GATA-1 modulates the transcription of tal-1 during the differentiation of the erythroid, megakaryocytic, and basosophilic lineages.