The transcriptional coregulator NAB2 is a target gene for the Wilms' tumor gene 1 protein (WT1) in leukemic cells
(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.
(Less)
- author
- 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
- organization
-
- Transcriptional mechanisms for the Wilms’ tumor gene 1 (WT1) oncoprotein (research group)
- Lymphoma - Clinical Research (research group)
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- Hematogenomics (research group)
- Division of Hematology and Transfusion Medicine
- publishing date
- 2017
- 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
- external identifiers
-
- scopus:85031718157
- wos:000413341400013
- pmid:29152069
- 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
- 2024-05-27 02:19:26
@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}}, keywords = {{Coregulator; Leukemia; NAB2; Target gene; WT1}}, language = {{eng}}, number = {{50}}, pages = {{87136--87150}}, publisher = {{Impact Journals}}, 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}}, doi = {{10.18632/oncotarget.19896}}, volume = {{8}}, year = {{2017}}, }