Transcription factors regulating the erytnroid and megakaryocytic cell differentiation.

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In the erythroid and megakaryocytic lineage cells, GATA-1 and GATA-2 show overlapping expression. The gene targeting experiments demonstrate that GATA-2 is essential for the hematopoietic stem and progenitor cells while GATA-1 expression is required for the terminal differentiation of both erythrocytes and megakaryocytes. We investigated the gene expression of GATA factors on leukemic cells and the transcriptional regulation of GATA-2 gene. The results are as follows ;1), GATA-1 and GATA-2 were expressed concomitantly on the leukemic cells with megakaryocytic or erythroid surface markers. GATA-2 mRNA was also detected in the myelogenous leukemia cells without any megakaryocytic or erythroid features. GATA-2 expression in leukemic cells were correlated with the c-kit antigen expression. This finding was consistent with the reports that GATA-2 has distinct functions in hematopoietic stem/progenitor cells.2), Transcription of mouse GATA-2 gene was found to initiate from two distinct first … More exons, both of which encode entirely untranslated regions, while the remaining five exons are shared by each of the two divergent mRNAs. Reverse transcriptase-polymerase chain reaction analysis revealed that GATA-2 mRNA initiated at the upstream first exon (IS) in Sca-1+/c-kit+hematopoieticprogenitor cells, whereas mRNA initiated at the downstream first exon (IG) is expressed in all tissues and cell lines that express GATA-2. While the structure of the IG exon/promoter shows high similarity to those of the Xenopus and human GATA-2 gene, the IS exon/promoter has not been described previously. Sequences lying between-79 and -61 are found to be critical for the cell type-specific activity of the IS promoter, and the binding of transcription factors to this region were demonstrated.3), A transgene containing the IS promoter and 6 kbp upstream region diercted expression of a reporter gene recapitulated the GATA-2 expression in aorta-gonads-mesonephros region and in bone marrow cells. Deletion analysis of the upstream region of IS promoter localized a hematopoietic enhancer activity between 3.5 to 2.5 kbp upstream of the IS exon. This region contained one of the DNaseI hypersensitve sites. Less