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The leukemia inhibitory factor receptor gene is a direct target of RUNX1

Citation

Qadi, A and Taberlay, PC and Phillips, JL and Young, A and West, AC and Brettingham-Moore, KH and Dickinson, JL and Holloway, AF, The leukemia inhibitory factor receptor gene is a direct target of RUNX1, Journal of Cellular Biochemistry, 117, (1) pp. 49-58. ISSN 0730-2312 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 Wiley Periodicals, Inc.

DOI: doi:10.1002/jcb.25246

Abstract

Activation of cytokine signaling via the leukemia inhibitory factor receptor (LIFR) plays an integral role in hematopoiesis, osteogenesis, and placental development, along with mediating neurotrophic mechanisms. However, the regulatory control of the LIFR gene has remained largely unexplored. Here, we characterize the LIFR gene as a novel target of the RUNX1 transcription factor. The RUNX1 transcription factor is an essential regulator of hematopoiesis and is a frequent target of point mutations and chromosomal alterations in leukemia. RUNX1 regulates hematopoiesis through its control of genes important for hematopoietic cell growth, proliferation, and differentiation, including a number of cytokines and cytokine receptors. LIFR is regulated by two alternate promoters: a placental-specific and a ubiquitously active general promoter. We show that both of these promoters are regulated by RUNX1. However, in myeloid cells LIFR expression is driven solely by the general LIFR promoter with our data indicating that the placental promoter is epigenetically silenced in these cells. While RUNX1 activates the LIFR general promoter, the oncogenic RUNX1-ETO fusion protein generated by the t(8;21) translocation commonly associated with acute myeloid leukemia represses promoter activity. The data presented here establish LIFR as a transcriptional target of RUNX1 and suggest that disruption of RUNX1 activity in myeloid cells may result in altered LIFR signaling in these cells.

Item Details

Item Type:Refereed Article
Keywords:LIFR, RUNX1, gene regulation
Research Division:Biological Sciences
Research Group:Genetics
Research Field:Epigenetics (incl. Genome Methylation and Epigenomics)
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Qadi, A (Ms Abeer Qadi)
Author:Taberlay, PC (Dr Phillippa Taberlay)
Author:Phillips, JL (Ms Jessica Phillips)
Author:Young, A (Miss Arabella Young)
Author:West, AC (Ms Alison West)
Author:Brettingham-Moore, KH (Dr Kate Brettingham-Moore)
Author:Dickinson, JL (Associate Professor Joanne Dickinson)
Author:Holloway, AF (Dr Adele Holloway)
ID Code:101263
Year Published:2015
Web of Science® Times Cited:1
Deposited By:Medicine (Discipline)
Deposited On:2015-06-15
Last Modified:2017-11-07
Downloads:0

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