GATA-1 and GATA-2 binding to 3′ enhancer of WT1 gene is essential for its transcription in acute leukemia and solid tumor cell lines
Although oncogenic functions and the clinical significance of Wilms tumor 1 ( WT1 ) have been extensively studied in acute leukemia, the regulatory mechanism of its transcription still remains to be determined. We found a significant correlation among the amounts of WT1, GATA-1 and GATA-2 mRNAs from...
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Published in | Leukemia Vol. 23; no. 7; pp. 1270 - 1277 |
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Main Authors | , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.07.2009
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | Although oncogenic functions and the clinical significance of Wilms tumor 1 (
WT1
) have been extensively studied in acute leukemia, the regulatory mechanism of its transcription still remains to be determined. We found a significant correlation among the amounts of
WT1, GATA-1
and
GATA-2
mRNAs from leukemia and solid tumor cell lines. Overexpression and small interfering RNA (siRNA) transfection experiments of
GATA-1
and
GATA-2
showed that these
GATA
transcription factors could induce WT1 expression. Promoter analysis showed that the 5′ promoter did not explain the different
WT1
mRNA levels between cell lines. The 3′ enhancer, especially the distal sites out of six putative GATA binding sites located within the region, but not the intron 3 enhancer, were essential for the
WT1
mRNA level. Electrophoretic mobility shift assay (EMSA) showed both GATA-1 and GATA-2 bound to these GATA sites. Besides acute leukemia cell lines, solid tumor cell lines including, TYK-nu-cPr also showed a high level of
WT1
mRNA. We showed that
GATA-2
expression is a determinant of
WT1
mRNA expression in both TYK-nu-cPr cells and HL60 cells without GATA-1 expression. Taken together, these results suggest that GATA-1 and/or GATA-2 binding to a GATA site of the 3′ enhancer of
WT1
played an important role in
WT1
gene expression. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0887-6924 1476-5551 |
DOI: | 10.1038/leu.2009.13 |