Evidence map›Paper›PMID 40032586›Full record

ArticleGenome research2025

Estrogen-induced chromatin looping changes identify a subset of functional regulatory elements.

Hosiana Abewe, Alexandra Richey, Jeffery M Vahrenkamp, Matthew Ginley-Hidinger, Craig M Rush, Noel Kitchen, Xiaoyang Zhang, Jason Gertz

Abstract read
In one paragraph

Article in Genome research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Hosiana AbeweHuntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.ORCID 0000-0003-3003-1177
Alexandra RicheyHuntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.ORCID 0009-0003-1297-8006
Jeffery M VahrenkampHuntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.ORCID 0000-0002-2937-1513
Matthew Ginley-HidingerHuntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.ORCID 0000-0001-5221-8878
Craig M RushHuntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.ORCID 0000-0002-1036-6909
Noel KitchenHuntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.
Xiaoyang ZhangHuntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA.ORCID 0000-0002-0031-0290
Jason GertzHuntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA; jay.gertz@hci.utah.edu.ORCID 0000-0001-7568-6789

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI KATHARINE S ULLMAN · 1986 to 2026
$72.6M
In situ evaluation of combinatorial gene regulation in the human genomeR01HG008974 · NHGRI · UNIVERSITY OF UTAH · PI GERTZ, JASON · 2017 to 2021
$3.2M
NCI NIH HHS P30 CA042014NHGRI NIH HHS R01 HG008974
6 · The paper itself

Abstract

Transcriptional enhancers can regulate individual or multiple genes through long-range three-dimensional (3D) genome interactions, and these interactions are commonly altered in cancer. Yet, the functional relationship between changes in 3D genome interactions associated with regulatory regions and differential gene expression appears context-dependent. In this study, we used HiChIP to capture changes in 3D genome interactions between active regulatory regions of endometrial cancer cells in response to estrogen treatment and uncovered significant differential long-range interactions strongly enriched for estrogen receptor alpha (ER, also known as ESR1)-bound sites (ERBSs). The ERBSs anchoring differential chromatin loops with either a gene's promoter or distal regions were correlated with larger transcriptional responses to estrogen compared with ERBSs not involved in differential 3D genome interactions. To functionally test this observation, CRISPR-based Enhancer-i was used to deactivate specific ERBSs, which revealed a wide range of effects on the transcriptional response to estrogen. However, these effects are only subtly and not significantly stronger for ERBSs in differential chromatin loops. In addition, we observed an enrichment of 3D genome interactions between the promoters of estrogen-upregulated genes and found that looped promoters can work together cooperatively. Overall, our work reveals that estrogen treatment causes large changes in 3D genome structure in endometrial cancer cells; however, these changes are not required for a regulatory region to contribute to an estrogen transcriptional response.

Indexed as

ChromatinEstrogensBinding SitesCell Line, TumorEndometrial NeoplasmsEnhancer Elements, GeneticEstrogen Receptor alphaFemaleGene Expression Regulation, NeoplasticHumansPromoter Regions, GeneticChromatinESR1 protein, humanEstrogen Receptor alphaEstrogens

Identifiers

PMID40032586
PMCPMC11960465

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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.