Evidence map›Paper›PMID 15342491›Full record

ArticleGenes & development2004

Attenuation of estrogen receptor alpha-mediated transcription through estrogen-stimulated recruitment of a negative elongation factor.

Sarah E Aiyar, Jian-long Sun, Ashley L Blair, Christopher A Moskaluk, Yun-zhe Lu, Qi-Nong Ye, Yuki Yamaguchi, Amitava Mukherjee, Da-ming Ren, Hiroshi Handa and 1 more

Open access · diamondAbstract readComparative Study
In one paragraph

Article in Genes & development, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
–field-weighted citation impact
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

72 citing papers in PubMed, 110 citations in OpenAlex.

  1. Review
  2. Article
  3. CDK9 keeps RNA polymerase II on track.Cellular and molecular life sciences : CMLS · 2021
    Review
  4. Article
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  9. Review
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  16. RNA polymerase II pausing as a context-dependent reader of the genome.Biochemistry and cell biology = Biochimie et biologie cellulaire · 2016
    Review
  17. Article
  18. Review
  19. Article
  20. A phosphotyrosine switch determines the antitumor activity of ERβ.The Journal of clinical investigation · 2014
    Article

12 more citing papers are in PubMed but not listed here.

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

11 authors at 3 institutions in 3 countries.

Sarah E AiyarDepartment of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, Virginia 22908-0733, USA.
Jian-long Sun
Ashley L Blair
Christopher A Moskaluk
Yun-zhe Lu
Qi-Nong Ye
Yuki Yamaguchi
Amitava Mukherjee
Da-ming Ren
Hiroshi Handa
Rong Li
Fudan University · CNUniversity of Virginia · USTokyo Institute of Technology · JP

Funding

A Novel Corepressor of Estrogen ReceptorR01DK064604 · NIDDK · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI LI, RONG · 2004 to 2007
$1.0M
Regulation of ER by BRCA1 and COBRA1F32CA099359 · NCI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI AIYAR, SARAH E · 2003 to 2003
$42k
NCI NIH HHS 1F32CA99359-01NCI NIH HHS F32 CA099359NIDDK NIH HHS R01 DK064604
6 · The paper itself

Abstract

Estrogen receptor alpha (ERalpha) signaling is paramount for normal mammary gland development and function and the repression of breast cancer. ERalpha function in gene regulation is mediated by a number of coactivators and corepressors, most of which are known to modify chromatin structure and/or influence the assembly of the regulatory complexes at the level of transcription initiation. Here we describe a novel mechanism of attenuating the ERalpha activity. We show that cofactor of BRCA1 (COBRA1), an integral subunit of the human negative elongation factor (NELF), directly binds to ERalpha and represses ERalpha-mediated transcription. Reduction of the endogenous NELF proteins in breast cancer cells using small interfering RNA results in elevated ERalpha-mediated transcription and enhanced cell proliferation. Chromatin immunoprecipitation reveals that recruitment of COBRA1 and the other NELF subunits to endogenous ERalpha-responsive promoters is greatly stimulated upon estrogen treatment. Interestingly, COBRA1 does not affect the estrogen-dependent assembly of transcription regulatory complexes at the ERalpha-regulated promoters. Rather, it causes RNA polymerase II (RNAPII) to pause at the promoter-proximal region, which is consistent with its in vitro biochemical activity. Therefore, our in vivo work defines the first corepressor of nuclear receptors that modulates ERalpha-dependent gene expression by stalling RNAPII. We suggest that this new level of regulation may be important to control the duration and magnitude of a rapid and reversible hormonal response.

Indexed as

Signal TransductionBlotting, NorthernCells, CulturedChromatinEstrogen Receptor alphaGene Expression RegulationHumansImmunohistochemistryLuciferasesNuclear ProteinsPlasmidsPrecipitin TestsPromoter Regions, GeneticReceptors, EstrogenReverse Transcriptase Polymerase Chain ReactionRNA Polymerase IIChromatinEstrogen Receptor alphaLuciferasesnegative elongation factorNuclear ProteinsReceptors, EstrogenRNA Polymerase IIRNA, Small InterferingTranscription Factors

Identifiers

PMID15342491
PMCPMC515291
OpenAlexW2100411328

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.