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Distinct mechanisms of regulation of the ITGA6 and ITGB4 genes by RUNX1 in myeloid cells

Citation

Phillips, JL and Taberlay, PC and Woodworth, AM and Hardy, K and Brettingham-Moore, KH and Dickinson, JL and Holloway, AF, Distinct mechanisms of regulation of the ITGA6 and ITGB4 genes by RUNX1 in myeloid cells, Journal of Cellular Physiology pp. 1-38. ISSN 0021-9541 (2017) [Refereed Article]


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DOI: doi:10.1002/jcp.26197

Abstract

Integrins are transmembrane adhesion receptors that play an important role in hematopoiesis by facilitating interactions between hematopoietic cells and extracellular matrix components of the bone marrow and hematopoietic tissues. These interactions are important in regulating the function, proliferation and differentiation of hematopoietic cells, as well as their homing and mobilization in the bone marrow. Not surprisingly altered expression and function of integrins plays a key role in the development and progression of cancer including leukemias. However, the regulation of integrin gene expression is not well characterized and the mechanisms by which integrin genes are disrupted in cancer remain unclear. Here we demonstrate for the first time that a key regulator of hematopoiesis, RUNX1, binds to and regulates the promoters of both the ITGA6 and ITGB4 genes in myeloid cells. The ITGA6 and ITGB4 integrin genes form the α6β4 integrin receptor. However our data indicates that RUNX1 functions differently at these two promoters. RUNX1 regulates ITGA6 through a consensus RUNX1 binding motif in its promoter. In contrast, although the ITGB4 promoter is also activated by RUNX1, it does so in the absence of a recognized consensus RUNX1 binding motif. Further, our data suggest that regulation of ITGB4 may involve interactions between the promoter and upstream regulatory elements. This article is protected by copyright. All rights reserved.

Item Details

Item Type:Refereed Article
Keywords:Gene expression, Integrin, RUNX1, Transcriptional regulation
Research Division:Medical and Health Sciences
Research Group:Oncology and Carcinogenesis
Research Field:Cancer Cell Biology
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Phillips, JL (Ms Jessica Phillips)
Author:Taberlay, PC (Dr Phillippa Taberlay)
Author:Woodworth, AM (Ms Alexandra Woodworth)
Author:Brettingham-Moore, KH (Dr Kate Brettingham-Moore)
Author:Dickinson, JL (Associate Professor Joanne Dickinson)
Author:Holloway, AF (Dr Adele Holloway)
ID Code:121350
Year Published:2017
Deposited By:Menzies Institute for Medical Research
Deposited On:2017-09-26
Last Modified:2017-10-19
Downloads:0

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