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

Authors :
Nilsson HJ
Montano G
Ullmark T
Lennartsson A
Drott K
Järvstråt L
Nilsson B
Vidovic K
Gullberg U
Source :
Oncotarget [Oncotarget] 2017 Aug 03; Vol. 8 (50), pp. 87136-87150. Date of Electronic Publication: 2017 Aug 03 (Print Publication: 2017).
Publication Year :
2017

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.<br />Competing Interests: CONFLICTS OF INTEREST The authors report no potential conflicts of interest.

Details

Language :
English
ISSN :
1949-2553
Volume :
8
Issue :
50
Database :
MEDLINE
Journal :
Oncotarget
Publication Type :
Academic Journal
Accession number :
29152069
Full Text :
https://doi.org/10.18632/oncotarget.19896