Evidence map›Paper›PMID 31905229›Full record

ArticlePLoS genetics2020

Ligand dependent gene regulation by transient ERα clustered enhancers.

Bharath Saravanan, Deepanshu Soota, Zubairul Islam, Sudeshna Majumdar, Rajat Mann, Sweety Meel, Umer Farooq, Kaivalya Walavalkar, Srimonta Gayen, Anurag Kumar Singh and 2 more

Open access · goldAbstract read
In one paragraph

Article in PLoS genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
1.4field-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

26 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Article
  16. Emerging insights into transcriptional condensates.Experimental & molecular medicine · 2024
    Review
  17. Article
  18. Article
  19. Review
  20. 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

12 authors at 3 institutions in 2 countries.

Bharath SaravananCellular Organization and Signalling, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
Deepanshu SootaCellular Organization and Signalling, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
Zubairul IslamCellular Organization and Signalling, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
Sudeshna MajumdarMolecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.ORCID 0000-0002-3039-0164
Rajat MannCellular Organization and Signalling, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
Sweety MeelCellular Organization and Signalling, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.ORCID 0000-0002-0010-7903
Umer FarooqCellular Organization and Signalling, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
Kaivalya WalavalkarCellular Organization and Signalling, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
Srimonta GayenMolecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, India.ORCID 0000-0002-8395-7283
Anurag Kumar SinghCellular Organization and Signalling, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.
Sridhar HannenhalliCancer Data Science Lab, National Cancer Institute, NIH, Bethesda, MD, United States of America.ORCID 0000-0001-9603-7569
Dimple NotaniCellular Organization and Signalling, National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore, India.ORCID 0000-0002-9460-8070
Tata Institute of Fundamental Research · INIndian Institute of Science Bangalore · INNational Cancer Institute · US

Funding

Machine learning, network-based models for gene expression, activity, functionZIABC011981 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI HANNENHALLI, SRIDHAR · 2020 to 2023
$1.2M
DBT-Wellcome Trust India Alliance IA/I/14/2/501539Wellcome TrustWellcome Trust IA/14/2/501539
6 · The paper itself

Abstract

Unliganded Estrogen receptor alpha (ERα) has been implicated in ligand-dependent gene regulation. Upon ligand exposure, ERα binds to several EREs relatively proximal to the pre-marked, unliganded ERα-bound sites and affects transient but robust gene expression. However, the underlying mechanisms are not fully understood. Here we demonstrate that upon ligand stimulation, persistent sites interact extensively, via chromatin looping, with the proximal transiently ERα-bound sites, forming Ligand Dependent ERα Enhancer Cluster in 3D (LDEC). The E2-target genes are regulated by these clustered enhancers but not by the H3K27Ac super-enhancers. Further, CRISPR-based deletion of TFF1 persistent site disrupts the formation of its LDEC resulting in the loss of E2-dependent expression of TFF1 and its neighboring genes within the same TAD. The LDEC overlap with nuclear ERα condensates that coalesce in a ligand and persistent site dependent manner. Furthermore, formation of clustered enhancers, as well as condensates, coincide with the active phase of signaling and their later disappearance results in the loss of gene expression even though persistent sites remain bound by ERα. Our results establish, at TFF1 and NRIP1 locus, a direct link between ERα condensates, ERα enhancer clusters, and transient, but robust, gene expression in a ligand-dependent fashion.

Indexed as

Chromatin Assembly and DisassemblyEnhancer Elements, GeneticEstrogen Receptor alphaGene DeletionHistonesHumansLigandsMCF-7 CellsTrefoil Factor-1Estrogen Receptor alphaHistonesLigandsTFF1 protein, humanTrefoil Factor-1

Identifiers

PMID31905229
PMCPMC6975561
OpenAlexW2997651447

What OpenQuestion holds

Textmetadata
LicenceCC0
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.