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

A. Furuhata, M. Murakami, H. Ito, S. Gao, K. Yoshida, S. Sobue, R. Kikuchi, T. Iwasaki, A. Takagi, T. Kojima, Motoshi Suzuki, A. Abe, T. Naoe, T. Murate

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Abstract

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.

Original languageEnglish
Pages (from-to)1270-1277
Number of pages8
JournalLeukemia
Volume23
Issue number7
DOIs
Publication statusPublished - 01-01-2009
Externally publishedYes

Fingerprint

Wilms' Tumor Genes
Wilms Tumor
Tumor Cell Line
Leukemia
Messenger RNA
GATA2 Transcription Factor
Cell Line
HL-60 Cells
Electrophoretic Mobility Shift Assay
Introns
Small Interfering RNA
Transfection
Binding Sites

All Science Journal Classification (ASJC) codes

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Furuhata, A. ; Murakami, M. ; Ito, H. ; Gao, S. ; Yoshida, K. ; Sobue, S. ; Kikuchi, R. ; Iwasaki, T. ; Takagi, A. ; Kojima, T. ; Suzuki, Motoshi ; Abe, A. ; Naoe, T. ; Murate, T. / 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. In: Leukemia. 2009 ; Vol. 23, No. 7. pp. 1270-1277.
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abstract = "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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Furuhata, A, Murakami, M, Ito, H, Gao, S, Yoshida, K, Sobue, S, Kikuchi, R, Iwasaki, T, Takagi, A, Kojima, T, Suzuki, M, Abe, A, Naoe, T & Murate, T 2009, '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', Leukemia, vol. 23, no. 7, pp. 1270-1277. https://doi.org/10.1038/leu.2009.13

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. / Furuhata, A.; Murakami, M.; Ito, H.; Gao, S.; Yoshida, K.; Sobue, S.; Kikuchi, R.; Iwasaki, T.; Takagi, A.; Kojima, T.; Suzuki, Motoshi; Abe, A.; Naoe, T.; Murate, T.

In: Leukemia, Vol. 23, No. 7, 01.01.2009, p. 1270-1277.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Furuhata, A.

AU - Murakami, M.

AU - Ito, H.

AU - Gao, S.

AU - Yoshida, K.

AU - Sobue, S.

AU - Kikuchi, R.

AU - Iwasaki, T.

AU - Takagi, A.

AU - Kojima, T.

AU - Suzuki, Motoshi

AU - Abe, A.

AU - Naoe, T.

AU - Murate, T.

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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.

AB - 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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