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Cited by 91Iron Metabolism and DisordersGenomics and Chromatin DynamicsHemoglobin structure and function

Transcriptional Regulation of the Ferritin Heavy-Chain Gene: the Activity of the CCAAT Binding Factor NF-Y Is Modulated in Heme-Treated Friend Leukemia Cells and during Monocyte-to-Macrophage Differentiation

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Marziali, G., Perrotti, E., Ilari, R., Testa, U., Coccia, E. M., Battistini, A.·1997·Molecular and Cellular Biology
DOI 10.1128/mcb.17.3.1387PMC PMC231863
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Abstract

The ferritin H-chain gene promoter regulation was analyzed in heme-treated Friend leukemia cells (FLCs) and during monocyte-to-macrophage differentiation. In the majority of cell lines studied, the regulation of ferritin expression was exerted mostly at the translational level. However, in differentiating erythroid cells, which must incorporate high levels of iron to sustain hemoglobin synthesis, and in macrophages, which are involved in iron storage, transcriptional regulation seemed to be a relevant mechanism. We show here that the minimum region of the ferritin H-gene promoter that is able to confer transcriptional regulation by heme in FLCs to a reporter gene is 77 nucleotides upstream of the TATA box. This cis element binds a protein complex referred to as HRF (heme-responsive factor), which is greatly enhanced both in heme-treated FLCs and during monocyte-to-macrophage differentiation. The CCAAT element present in reverse orientation in this promoter region of the ferritin H-chain gene is necessary for binding and for gene activity, since a single point mutation is able to abolish the binding of HRF and the transcriptional activity in transfected cells. By competition experiments and supershift assays, we identified the induced HRF as containing at least the ubiquitous transcription factor NF-Y. NF-Y is formed by three subunits, A, B, and C, all of which are necessary for DNA binding. Cotransfection with a transdominant negative mutant of the NF-YA subunit abolishes the transcriptional activation by heme, indicating that NF-Y plays an essential role in this activation. We have also observed a differential expression of the NF-YA subunit in heme-treated and control FLCs and during monocyte-to-macrophage differentiation.

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Authors
Marziali, G., Perrotti, E., Ilari, R., Testa, U., Coccia, E. M., & Battistini, A.
Affiliations
Istituto Superiore di Sanità (IT)
ORCID
Venue
Molecular and Cellular Biology
Publisher
Informa UK Limited
Published
1997-03-01
Volume
17
Issue
3
Pages
1387-1395
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
DOI
10.1128/mcb.17.3.1387
PMC
PMC231863
OpenAlex
W1896728310
Cited by
91
References
46
Citations by year
2020: 1 · 2019: 2 · 2018: 1 · 2017: 1 · 2016: 1 · 2014: 2 · 2013: 2
FWCI
4.80
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Molecular and Cellular Biology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Consiglio Nazionale delle Ricerche
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
Keywords
transcriptional regulation, NF-Y, CCAAT box, heme, Friend leukemia cells, monocyte-to-macrophage differentiation, erythroid cells, iron metabolism, NF-YA, promoter cis-acting elements, transcription factor binding
MeSH terms
Adult, Binding Sites, Cell Differentiation, DNA-Binding Proteins, DNA, Neoplasm, Leukemia, Erythroblastic, Acute, Female, Ferritins, Friend murine leukemia virus, Gene Expression Regulation, Hemin, Humans, Macrophages, Monocytes, Promoter Regions, Genetic, Transcription Factors, Transcription, Genetic, Tumor Cells, Cultured, Erythroid Precursor Cells, Sp1 Transcription Factor, Point Mutation, CCAAT-Enhancer-Binding Proteins, In Vitro Techniques

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