The transcriptional coregulator NAB2 is a target gene for the Wilms' tumor gene 1 protein (WT1) in leukemic cells

The Wilms' tumor gene 1 ( ) is recurrently mutated in acute myeloid leukemia. Mutations and high expression of associate with a poor prognosis. In mice, WT1 cooperates with the ( ) fusion gene in the induction of acute leukemia, further emphasizing a role for WT1 in leukemia development. Molecu...

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Bibliographic Details
Published in:Oncotarget 2017-10, Vol.8 (50), p.87136-87150
Main Authors: Nilsson, Helena Jernmark, Montano, Giorgia, Ullmark, Tove, Lennartsson, Andreas, Drott, Kristina, Järvstråt, Linnea, Nilsson, Björn, Vidovic, Karina, Gullberg, Urban
Format: Article
Language:English
Subjects:
Coregulator
Leukemia
Medicin och hälsovetenskap
NAB2
Research Paper
Target gene
WT1
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Summary:The Wilms' tumor gene 1 ( ) is recurrently mutated in acute myeloid leukemia. Mutations and high expression of associate with a poor prognosis. In mice, WT1 cooperates with the ( ) 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 as a target gene of WT1. Analysis of gene expression profiles of leukemic samples revealed a positive correlation between the expression of and , as well as a non-zero partial correlation. Overexpression of in hematopoietic cells resulted in increased levels, while suppression of decreased expression. WT1 bound and transactivated the proximal promoter, as shown by ChIP and reporter experiments, respectively. ChIP experiments also revealed that WT1 can recruit NAB2 to the promoter, thus modulating the transcriptional activity of WT1, as shown by reporter experiments. Our results implicate as a previously unreported target gene of WT1 and that NAB2 acts as a transcriptional cofactor of WT1.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.19896