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

Helena Jernmark Nilsson, Giorgia Montano, Tove Ullmark, Andreas Lennartsson, Kristina Drott, Linnea Järvstråt, Björn Nilsson, Karina Vidovic, Urban Gullberg

Research output: Contribution to journalArticlepeer-review

3 Citations (SciVal)

Abstract

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.

Original languageEnglish
Pages (from-to)87136-87150
JournalOncotarget
Volume8
Issue number50
DOIs
Publication statusPublished - 2017

Keywords

  • Coregulator
  • Leukemia
  • NAB2
  • Target gene
  • WT1

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