The transcriptional coregulator NAB2 is a target gene for the Wilms' tumor gene 1 protein (WT1) in leukemic cells
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Helena Jernmark Nilsson1, Giorgia Montano1, Tove Ullmark1, Andreas Lennartsson2, Kristina Drott1, Linnea Järvstråt1, Björn Nilsson1, Karina Vidovic1 and Urban Gullberg1
1Division of Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden
2Department of Biosciences and Nutrition, Karolinska Institutet, Huddinge, Sweden
Urban Gullberg, email: [email protected]
Keywords: WT1, NAB2, target gene, coregulator, leukemia
Received: October 29, 2016 Accepted: July 13, 2017 Published: August 03, 2017
The Wilms’ tumor gene 1 (WT1) is recurrently mutated in acute myeloid leukemia. Mutations and high expression of WT1 associate with a poor prognosis. In mice, WT1 cooperates with the RUNX1/RUNX1T1 (AML1/ETO) fusion gene in the induction of acute leukemia, further emphasizing a role for WT1 in leukemia development. Molecular mechanisms for WT1 are, however, incompletely understood. Here, we identify the transcriptional coregulator NAB2 as a target gene of WT1. Analysis of gene expression profiles of leukemic samples revealed a positive correlation between the expression of WT1 and NAB2, as well as a non-zero partial correlation. Overexpression of WT1 in hematopoietic cells resulted in increased NAB2 levels, while suppression of WT1 decreased NAB2 expression. WT1 bound and transactivated the proximal NAB2 promoter, as shown by ChIP and reporter experiments, respectively. ChIP experiments also revealed that WT1 can recruit NAB2 to the IRF8 promoter, thus modulating the transcriptional activity of WT1, as shown by reporter experiments. Our results implicate NAB2 as a previously unreported target gene of WT1 and that NAB2 acts as a transcriptional cofactor of WT1.
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