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Regulation and function of the NFE2 transcription factor in hematopoietic and non-hematopoietic cells

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Abstract

The NFE2 transcription factor was identified over 25 years ago. The NFE2 protein forms heterodimers with small MAF proteins, and the resulting complex binds to regulatory elements in a large number of target genes. In contrast to other CNC transcription family members including NFE2L1 (NRF1), NFE2L2 (NRF2) and NFE2L3 (NRF3), which are widely expressed, earlier studies had suggested that the major sites of NFE2 expression are hematopoietic cells. Based on cell culture studies it was proposed that this protein acts as a critical regulator of globin gene expression. However, the knockout mouse model displayed only mild erythroid abnormalities, while the major phenotype was a defect in megakaryocyte biogenesis. Indeed, absence of NFE2 led to severely impaired platelet production. A series of recent data, also summarized here, shed new light on the various functional roles of NFE2 and the regulation of its activity. NFE2 is part of a complex regulatory network, including transcription factors such as GATA1 and RUNX1, controlling megakaryocytic and/or erythroid cell function. Surprisingly, it was recently found that NFE2 also has a role in non-hematopoietic tissues, such as the trophoblast, in which it is also expressed, as well as the bone, opening the door to new research areas for this transcription factor. Additional data showed that NFE2 function is controlled by a series of posttranslational modifications. Important strides have been made with respect to the clinical significance of NFE2, linking this transcription factor to hematological disorders such as polycythemias.

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Acknowledgments

This work was supported by a McGill University Faculty of Medicine internal studentship and a joint fellowship from the CIHR and the Thalassemia Foundation of Canada to JG. We would also like to acknowledge grants from the Thalassemia Foundation of Canada as well as CIHR (MOP-79361 and MOP-97932) to VB.

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  1. Lady Davis Institute for Medical Research, McGill University, 3755 Chemin de la Côte Sainte-Catherine, Montreal, QC, H3T 1E2, Canada

    Jadwiga J. Gasiorek & Volker Blank

  2. Department of Medicine, McGill University, Montreal, QC, Canada

    Jadwiga J. Gasiorek & Volker Blank

  3. Department of Physiology, McGill University, Montreal, QC, Canada

    Volker Blank

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  1. Jadwiga J. Gasiorek
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Correspondence to Volker Blank.

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Gasiorek, J.J., Blank, V. Regulation and function of the NFE2 transcription factor in hematopoietic and non-hematopoietic cells. Cell. Mol. Life Sci. 72, 2323–2335 (2015). https://doi.org/10.1007/s00018-015-1866-6

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  • DOI: https://doi.org/10.1007/s00018-015-1866-6

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