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

Nilsson, Helena Jernmark LU ; Montano, Giorgia LU ; Ullmark, Tove LU ; Lennartsson, Andreas LU ; Drott, Kristina LU ; Järvstråt, Linnea LU ; Nilsson, Björn LU ; Vidovic, Karina LU and Gullberg, Urban LU (2017) In Oncotarget 8(50). p.87136-87150
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... (More)

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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author
organization
publishing date
type
Contribution to journal
publication status
published
keywords
Coregulator, Leukemia, NAB2, Target gene, WT1
in
Oncotarget
volume
8
issue
50
pages
87136 - 87150
publisher
Impact Journals, LLC
external identifiers
  • scopus:85031718157
  • wos:000413341400013
ISSN
1949-2553
DOI
10.18632/oncotarget.19896
language
English
LU publication?
yes
id
7318c106-5bb4-43f5-b40f-8b07def11492
date added to LUP
2017-11-15 12:54:05
date last changed
2018-10-31 19:56:58
@article{7318c106-5bb4-43f5-b40f-8b07def11492,
  abstract     = {<p>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.</p>},
  author       = {Nilsson, Helena Jernmark and Montano, Giorgia and Ullmark, Tove and Lennartsson, Andreas and Drott, Kristina and Järvstråt, Linnea and Nilsson, Björn and Vidovic, Karina and Gullberg, Urban},
  issn         = {1949-2553},
  keyword      = {Coregulator,Leukemia,NAB2,Target gene,WT1},
  language     = {eng},
  number       = {50},
  pages        = {87136--87150},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {The transcriptional coregulator NAB2 is a target gene for the Wilms' tumor gene 1 protein (WT1) in leukemic cells},
  url          = {http://dx.doi.org/10.18632/oncotarget.19896},
  volume       = {8},
  year         = {2017},
}