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Expression of tal-1 and GATA-binding proteins during human hematopoiesis
MA Mouthon, O Bernard, MT Mitjavila, PH Romeo, W Vainchenker and D Mathieu-Mahul
INSERM 91, Hopital Henri Mondor, Creteil, France.
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.
Volume 81,
Issue 3,
pp. 647-655,
02/01/1993
Copyright © 1993 by The American Society of Hematology
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