Evidence map›Paper›PMID 29378668›Full record

ArticleEpigenetics & chromatin2018

Genome-wide analysis reveals a role for TDG in estrogen receptor-mediated enhancer RNA transcription and 3-dimensional reorganization.

Bart Kolendowski, Haider Hassan, Milica Krstic, Majdina Isovic, Gobi Thillainadesan, Ann F Chambers, Alan B Tuck, Joseph Torchia

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epigenetics & chromatin, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
0.7field-weighted citation impact, top 30% 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

18 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Roles of enhancer RNAs in sex hormone-dependent cancers.Journal of cancer research and clinical oncology · 2022
    Review
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Review
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

8 authors at 2 institutions in 1 country.

Bart KolendowskiDepartment of Biochemistry, Western University, London, ON, Canada.
Haider HassanDepartment of Biochemistry, Western University, London, ON, Canada.
Milica KrsticDepartment of Pathology, Western University, London, ON, Canada.
Majdina IsovicDepartment of Oncology, Western University, London, ON, Canada.
Gobi ThillainadesanDepartment of Biochemistry, Western University, London, ON, Canada.
Ann F ChambersThe London Regional Cancer Program and the Lawson Health Research Institute, Western University, London, ON, Canada.
Alan B TuckDepartment of Oncology, Western University, London, ON, Canada.
Joseph TorchiaDepartment of Biochemistry, Western University, London, ON, Canada. jtorchia@uwo.ca.
Western University · CALawson Health Research Institute · CA

Funding

CIHR MOP84423
6 · The paper itself

Abstract

backgroundThe estrogen receptor (ER) is a ligand-dependant transcription factor expressed in many breast cancers and is the target of many endocrine-based cancer therapies. Genome-wide studies have shown that the ER binds to gene-specific enhancer regions in response to β-estradiol (E2) which undergo transcription producing noncoding enhancer RNA (eRNA). While eRNAs are important for transcriptional activation of neighboring genes, the mechanism remains poorly understood.

resultsUsing ChIP-Seq we generate a global profile of thymine DNA glycosylase (TDG), an ER coactivator that plays an essential role in DNA demethylation, in response to E2 in the MCF7 breast cancer cell line. Remarkably, we found that in response to E2 TDG localized to enhancers which also recruit ERα, RNA Pol II and other coregulators and which are marked by histone modifications indicative of active enhancers. Importantly, depletion of TDG inhibits E2-mediated transcription of eRNAs and transcription of ER-target genes. Functionally, we find that TDG both sensitizes MCF7 cells to tamoxifen-mediated cytostasis and increases migration and invasion of MCF7 cells.

conclusionsTaken together we find that TDG plays a central role in mediating transcription at a subset of enhancers and governs how MCF7 cells respond to both estrogenic and anti-estrogenic compounds and may be an effective therapeutic target.

Indexed as

Enhancer Elements, GeneticBreast NeoplasmsCell MovementCell ProliferationCell SurvivalChromatin ImmunoprecipitationDNA MethylationDrug SynergismEstradiolFemaleHumansMCF-7 CellsReceptors, EstrogenRNA Polymerase IISequence Analysis, RNATamoxifenEstradiolReceptors, EstrogenRNA Polymerase IITamoxifenThymine DNA GlycosylaseCancereRNAEstrogen receptorEstrogen signalingThymine DNA glycosylase

Identifiers

PMID29378668
PMCPMC5787930
OpenAlexW2789023130

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.