GATA-1 Transactivates the WT1 Hematopoietic Specific Enhancer (*)
- From the Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030
- ¶ To whom all correspondence should be addressed.
Abstract
The Wilms' tumor gene, WT1, is believed to play a role in hematopoiesis as it is expressed in the spleen and in immature leukemias in addition to the developing genitourinary system. WT1 is down-regulated in differentiated leukemia cells both in vivo and in vitro and is up-regulated in fetal spleen and immature leukemia cells. The modulation of WT1 expression was examined in many cell types, and a hematopoietic-specific enhancer element has been identified. Here we describe the transcriptional response of this enhancer to hematopoietic-specific transcription factors. We found co-expression of WT1 and GATA-1 mRNA in K562 cells and in mouse spleen, suggesting potential interactions between these two transcription factors. We find that the activity of the 3′ WT1 enhancer is positively correlated with the expression of GATA-1. Gel shift competition experiments and transactivation studies revealed that this functional activity is mediated via binding at a GATA-binding site in the WT1 enhancer. The transactivation of the WT1 enhancer by GATA-1 implies that GATA-1 plays a role in the regulation of WT1 during hematopoiesis.
Footnotes
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↵* This work was supported by National Institutes of Health Grant CA 34936 and Core Grant CA 16672. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵1 The abbreviations used are:
- bp
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base pair(s)
- kb
-
kilobase(s)
- ALL
-
acute lymphocytic leukemia
- PCR
-
polymerase chain reaction
- CAT
-
chloramphenicol acetyltransferase.
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- Received December 14, 1994.
- Revision received January 17, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
