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Molecular Biology of Hematopoiesis 6 pp 391–402Cite as

Transcriptional Regulation of the Ferritin H-Chain and Transferrin Receptor in Hematopoietic Cells

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Abstract

The mechanisms that regulate the ferritin and transferrin receptor (TfR) expression in response to variation in the cellular iron supply have been extensively studied and represent a model of coordinate post-transcriptional regulation. However, additional mechanisms are operative in hematopoietic cells where high levels of iron are required to sustain specific cell requirements. We investigated the transcriptional regulation of the two main molecules involved in iron metabolism i.e. TfR and ferritin, which are both upregulated during erythroid differentiation. Friend leukemia cells (FLCs) treated with heme or induced to terminally differentiate with dimethylsulfoxide (DMSO), were used as experimental model. By transfection experiments, we identified a minimum region of 77 nucleotides (nt) upstream the TATA box of the ferritin H-gene promoter able to confer transcriptional regulation to a reporter gene in heme-treated FLCs. The CCAAT element present in reverse orientation in this promoter region is necessary for gene activity and binds a protein complex, greatly enhanced in heme-treated FLCs, and containing the heteromeric and ubiquitous transcription factor NF-Y. Similarly we identified in the TfR gene promoter, a region of 500 base pairs (bp) starting from the transcription start site able to confer transcriptional inducibility in FLCs induced to differentiate by DMSO treatment. We conclude that transcriptional induction of both ferritin and TfR plays a relevant role in the regulation of the synthesis of these two molecules in erythroid cells and is not operative in other cell types (e.g. fibroblastic cell lines).

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Author information

Authors and Affiliations

  1. Departments of Virology Hematology and Oncology, Immunology, Istituto Superiore di Sanità, Rome, Italy

    Giovanna Marziali, Edvige Perrotti, Ramona Ilari, Eliana M. Coccia, Ugo Testa & Angela Battistini PhD

  2. Departments of Virology Hematology and Oncology, Immunology, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161, Rome, Italy

    Angela Battistini PhD

Authors
  1. Giovanna Marziali
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  2. Edvige Perrotti
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  3. Ramona Ilari
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  4. Eliana M. Coccia
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  5. Ugo Testa
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  6. Angela Battistini PhD
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Editor information

Editors and Affiliations

  1. New York Medical College, Valhalla, New York, USA

    Nader G. Abraham

  2. University of Perugia, Perugia, Italy

    Antonio Tabilio  & Massimo Martelli  & 

  3. University of Tokyo, Tokyo, Japan

    Shigetaka Asano

  4. Bambino Gesu Hospital, Rome, Italy

    Alberto Donfrancesco

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© 1999 Springer Science+Business Media New York

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Marziali, G., Perrotti, E., Ilari, R., Coccia, E.M., Testa, U., Battistini, A. (1999). Transcriptional Regulation of the Ferritin H-Chain and Transferrin Receptor in Hematopoietic Cells. In: Abraham, N.G., Tabilio, A., Martelli, M., Asano, S., Donfrancesco, A. (eds) Molecular Biology of Hematopoiesis 6. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4797-6_48

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  • DOI: https://doi.org/10.1007/978-1-4615-4797-6_48

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7173-1

  • Online ISBN: 978-1-4615-4797-6

  • eBook Packages: Springer Book Archive

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