Evidence map›Paper›PMID 9857194›Full record

ArticleThe EMBO journal1998

Leukemic transformation by the v-ErbA oncoprotein entails constitutive binding to and repression of an erythroid enhancer in vivo.

P Ciana, G G Braliou, F G Demay, M von Lindern, D Barettino, H Beug, H G Stunnenberg

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.3field-weighted citation impact, top 19% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 35 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 2 countries.

P CianaGene Expression Program, EMBL, Meyerhofstrasse 1, D-69117 Heidelberg, Germany.
G G Braliou
F G Demay
M von Lindern
D Barettino
H Beug
H G Stunnenberg
University of Milan · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

v-ErbA, a mutated thyroid hormone receptor alpha (TRalpha), is thought to contribute to avian erythroblastosis virus (AEV)-induced leukemic transformation by constitutively repressing transcription of target genes. However, the binding of v-ErbA or any unliganded nuclear receptor to a chromatin-embedded response element as well as the role of the N-CoR-SMRT-HDAC co-repressor complex in mediating repression remain hypothetical. Here we identify a v-ErbA-response element, VRE, in an intronic DNase I hypersensitive site (HS2) of the chicken erythroid carbonic anhydrase II (CAII) gene. In vivo footprinting shows that v-ErbA is constitutively bound to this HS2-VRE in transformed, undifferentiated erythroblasts along with other transcription factors like GATA-1. Transfection assays show that the repressed HS2 region can be turned into a potent enhancer in v-ErbA-expressing cells by mutation of the VRE. Differentiation of transformed cells alleviates v-ErbA binding concomitant with activation of CAII transcription. Co-expression of a gag-TRalpha fusion protein in AEV-transformed cells and addition of ligand derepresses CAII transcription. Treatment of transformed cells with the histone deacetylase inhibitor, trichostatin A, derepresses the endogenous, chromatin-embedded CAII gene, while a transfected HS2-enhancer construct remains repressed. Taken together, our data suggest that v-ErbA prevents CAII activation by 'neutralizing' in cis the activity of erythroid transcription factors.

Indexed as

Cell Transformation, NeoplasticResponse ElementsAlpharetrovirusAnimalsBase SequenceCarbonic AnhydrasesCell DifferentiationDNA FootprintingEnhancer Elements, GeneticErythropoiesisGene Expression Regulation, NeoplasticHistone Deacetylase InhibitorsHydroxamic AcidsIntronsLeukemiaMolecular Sequence DataCarbonic AnhydrasesHistone Deacetylase InhibitorsHydroxamic AcidsOncogene Proteins v-erbAReceptors, Thyroid Hormonetrichostatin A

Identifiers

PMID9857194
PMCPMC1171083
OpenAlexW2152492183

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.