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

Blood. 1993 Feb 1;81(3):647-55.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD / analysis
  • Antigens, CD34
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • Blood Platelets / physiology*
  • Bone Marrow / physiology
  • Cell Line
  • Child
  • DNA-Binding Proteins / genetics*
  • Erythroid-Specific DNA-Binding Factors
  • Exons
  • 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 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

Substances

  • Antigens, CD
  • Antigens, CD34
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • GATA1 Transcription Factor
  • GATA1 protein, human
  • Oligodeoxyribonucleotides
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • T-Cell Acute Lymphocytic Leukemia Protein 1
  • Transcription Factors
  • TAL1 protein, human