Evidence map›Paper›PMID 25486255›Full record

ArticlePloS one2014

CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells.

Yan Li, Chloe M Rivera, Haruhiko Ishii, Fulai Jin, Siddarth Selvaraj, Ah Young Lee, Jesse R Dixon, Bing Ren

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 129 papers.

0numbers the graph read from it
0cells of the map it votes in
129citing papers in PubMed
8.4field-weighted citation impact, top 2% 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

129 citing papers in PubMed, 216 citations in OpenAlex.

  1. Article
  2. TheiScience · 2026
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  7. Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026
    Review
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69 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

8 authors at 1 institution in 1 country.

Yan LiLudwig Institute for Cancer Research, San Diego, California, United States of America.
Chloe M RiveraLudwig Institute for Cancer Research, San Diego, California, United States of America; The Biomedical Sciences Graduate Program, University of California San Diego, School of Medicine, San Diego, California, United States of America.
Haruhiko IshiiLudwig Institute for Cancer Research, San Diego, California, United States of America.
Fulai JinLudwig Institute for Cancer Research, San Diego, California, United States of America.
Siddarth SelvarajLudwig Institute for Cancer Research, San Diego, California, United States of America.
Ah Young LeeLudwig Institute for Cancer Research, San Diego, California, United States of America.
Jesse R DixonLudwig Institute for Cancer Research, San Diego, California, United States of America; Medical Scientist Training Program, University of California San Diego, School of Medicine, San Diego, California, United States of America.
Bing RenLudwig Institute for Cancer Research, San Diego, California, United States of America; Department of Cellular and Molecular Medicine, Institute of Genome Medicine, Moores Cancer Center, University of California San Diego, School of Medicine, San Diego, California, United States of America.
Ludwig Cancer Research · US

Funding

MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI CHI, NEIL C, INSEL, PAUL A · 1985 to 2024
$29.3M
Center for Mammalian Regulatory GenomicsU54HG006997 · NHGRI · LUDWIG INSTITUTE FOR CANCER RES LTD · PI REN, BING · 2012 to 2016
$14.3M
Training Program in Basic Clinical GeneticsT32GM008666 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HAMILTON, BRUCE A · 1998 to 2021
$8.6M
NHGRI NIH HHS U54 HG006997NIGMS NIH HHS T32 GM007198NIGMS NIH HHS T32 GM008666
6 · The paper itself

Abstract

The pluripotency of embryonic stem cells (ESCs) is maintained by a small group of master transcription factors including Oct4, Sox2 and Nanog. These core factors form a regulatory circuit controlling the transcription of a number of pluripotency factors including themselves. Although previous studies have identified transcriptional regulators of this core network, the cis-regulatory DNA sequences required for the transcription of these key pluripotency factors remain to be defined. We analyzed epigenomic data within the 1.5 Mb gene-desert regions around the Sox2 gene and identified a 13kb-long super-enhancer (SE) located 100kb downstream of Sox2 in mouse ESCs. This SE is occupied by Oct4, Sox2, Nanog, and the mediator complex, and physically interacts with the Sox2 locus via DNA looping. Using a simple and highly efficient double-CRISPR genome editing strategy we deleted the entire 13-kb SE and characterized transcriptional defects in the resulting monoallelic and biallelic deletion clones with RNA-seq. We showed that the SE is responsible for over 90% of Sox2 expression, and Sox2 is the only target gene along the chromosome. Our results support the functional significance of a SE in maintaining the pluripotency transcription program in mouse ESCs.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsEnhancer Elements, GeneticAnimalsCell LineChromosome MappingComputational BiologyEmbryonic Stem CellsEpigenesis, GeneticGene DeletionGene Expression RegulationMiceSOXB1 Transcription FactorsTranscription, GeneticSOXB1 Transcription Factors

Identifiers

PMID25486255
PMCPMC4259346
OpenAlexW2050090238

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.