Cited by 123Hemoglobin structure and functionGenomics and Chromatin DynamicsCytokine Signaling Pathways and Interactions

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The human haptoglobin gene: transcriptional regulation during development and acute phase induction

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Oliviero, S., Morrone, G., Cortese, R.·1987·The EMBO Journal

DOI 10.1002/j.1460-2075.1987.tb02450.xPMC PMC553575

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Abstract

Haptoglobin is a plasma protein scarcely present in fetal but abundant in adult serum, where it is present at a concentration of approximately 150 mg/100 ml. In this paper we show by run-on experiments that the haptoglobin (Hp) gene is actively transcribed in adult but not in fetal liver nuclei. Studies with established cell lines indicate that the Hp gene is expressed in the hepatoma cells HepG2 but not in the hepatoma cell line Hep3B nor in HeLa cells. Plasmids carrying various segments of the 5' flanking region of the Hp gene fused to the chloramphenicol acetyl transferase (CAT) gene direct CAT transcription when introduced into HepG2 but are inactive in Hep3B and in HeLa cells, thus behaving like the resident chromosomal Hp gene. Deletion analysis defines a region, upstream to the transcription initiation site, essential for cell-specific expression. The Hp gene is induced in Hep3B cells by treatment with supernatant from LPS-stimulated monocytes (SMS), in a manner mimicking the acute phase reaction. We characterize the DNA segment necessary and sufficient for cell-specific expression of the Hp-CAT constructions in HepG2 and show that the same segment is also sufficient for acute phase induction in Hep3B.

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STUDY OF SERUM HAPTOGLOBIN LEVEL AND ITS RELATION TO ERYTHROPOIETIC ACTIVITY IN BETA THALASSEMIA CHILDREN .
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“Increased production of Hp is the result of transcriptional activation of the Hp gene (Baumann & Jahreis, 1983; Oliviero et al., 1987) by pro-inflammatory cytokines such as interleukin(IL)-1, IL-6, and Tumor Necrosis factor (TNF) (Baumann et al., 1989).”
Background
Low plasma haptoglobin is a risk factor for life-threatening childhood severe malarial anemia and not an exclusive consequence of hemolysis
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“The major inducer of the expression of Hp is IL-6, which is produced through the activities of the primary cytokines TNF-α and IL-1 [19].”
Background
An intronic endogenous retrovirus-like sequence attenuates human haptoglobin-related gene expression in an orientation-dependent manner
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“(20) (42) (21) (2) (46) 12 27 -139 -152 -51 -108 -159 -61”
Background
An Inducible 50-Kilodalton NFκB-Like Protein and a Constitutive Protein Both Bind the Acute-Phase Response Element of the Angiotensinogen Gene
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Determination of haptoglobin expression in IL-6 treated HepG2 cells by ELISA and by RNA hybridization — Evaluation of a quantitative method to measure IL-6
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Characterization of an IL‐6‐responsive Element (IL6RE) Present on Liver‐specific Genes and Identification of the Cognate IL‐6‐dependent DNA‐binding Protein (IL6DBP)a
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“IL-6 is an major inducer of this protein [34].”
Background
Transcriptionally Active Haptoglobin-Related (Hpr) Gene in Hepatoma G 2 and Leukemia Molt-4 Cells
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“Nuclear run-on experiments have shown that Hpr is not transcribed in either fetal or adult liver, although it does not have any of the features commonly associated with pseudogenes (Oliviero et al., 1987; Bensi ef al, 1985).”
Influential

Authors: Oliviero, S., Morrone, G., & Cortese, R.
Affiliations: European Molecular Biology Laboratory (DE)
ORCID: Oliviero, S.
Morrone, G.
Cortese, R.
Venue: The EMBO Journal
Publisher: Springer Science and Business Media LLC
Published: 1987-07-01
Volume: 6
Issue: 7
Pages: 1905-1912
ISSN: 0261-4189 (ISSN-L)
1460-2075
DOI: 10.1002/j.1460-2075.1987.tb02450.x
PMC: PMC553575
OpenAlex: W408517226
Cited by: 123
References: 33
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 2 · 2018: 3 · 2017: 2 · 2015: 3 · 2014: 2 · 2012: 1
FWCI: 8.83
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: The EMBO Journal (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
Use Siena air (University of Siena) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Hemoglobin structure and function
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords: transcriptional regulation, acute phase response, fetal liver, hepatoma cell lines, HepG2 cells, Hep3B cells, 5'-flanking region, cell type-specific gene expression, chloramphenicol acetyltransferase reporter, developmental gene expression
MeSH terms: Adult, Base Sequence, Cell Line, Cloning, Molecular, Fetus, Gene Expression Regulation, Genes, Haptoglobins, HeLa Cells, Carcinoma, Hepatocellular, Humans, Liver, Liver Neoplasms, Molecular Sequence Data, Plasmids, Transcription, Genetic

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The human haptoglobin gene: transcriptional regulation during development and acute phase induction

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