Evidence map›Paper›PMID 26813977›Full record

ArticleGenome research2016

A new class of temporarily phenotypic enhancers identified by CRISPR/Cas9-mediated genetic screening.

Yarui Diao, Bin Li, Zhipeng Meng, Inkyung Jung, Ah Young Lee, Jesse Dixon, Lenka Maliskova, Kun-Liang Guan, Yin Shen, Bing Ren

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.

0numbers the graph read from it
0cells of the map it votes in
83citing 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

83 citing papers in PubMed, 126 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Rewriting regulatory DNA to dissect and reprogram gene expression.bioRxiv : the preprint server for biology · 2023
    Article
  18. Review
  19. Article
  20. Review

23 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

10 authors at 3 institutions in 2 countries.

Yarui DiaoLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, California 92093, USA;
Bin LiLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, California 92093, USA;
Zhipeng MengDepartment of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA;
Inkyung JungLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, California 92093, USA;
Ah Young LeeLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, California 92093, USA;
Jesse DixonLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, California 92093, USA; Medical Scientist Training Program, University of California, San Diego, La Jolla, California 92093, USA; Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, California 92093, USA;
Lenka MaliskovaInstitute for Human Genetics and Department of Neurology, University of California, San Francisco, San Francisco, California 94143, USA;
Kun-Liang GuanDepartment of Pharmacology and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA;
Yin ShenInstitute for Human Genetics and Department of Neurology, University of California, San Francisco, San Francisco, California 94143, USA;
Bing RenLudwig Institute for Cancer Research, University of California, San Diego, La Jolla, California 92093, USA; Department of Cellular and Molecular Medicine, Institute of Genomic Medicine and Moores Cancer Center, University of California, San Diego, La Jolla, California 92093, USA.
Ludwig Cancer Research · BEUniversity of California San Diego · USUniversity of California, San Francisco · US

Funding

SYNTHETIC SYSTEMSP50GM085764 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI HASTY, JEFF M, IDEKER, TREY · 2010 to 2018
$23.3M
NIGMS NIH HHS 2P50 GM085764NIGMS NIH HHS P50 GM085764
6 · The paper itself

Abstract

With <2% of the human genome coding for proteins, a major challenge is to interpret the function of the noncoding DNA. Millions of regulatory sequences have been predicted in the human genome through analysis of DNA methylation, chromatin modification, hypersensitivity to nucleases, and transcription factor binding, but few have been shown to regulate transcription in their native contexts. We have developed a high-throughput CRISPR/Cas9-based genome-editing strategy and used it to interrogate 174 candidate regulatory sequences within the 1-Mbp POU5F1 locus in human embryonic stem cells (hESCs). We identified two classical regulatory elements, including a promoter and a proximal enhancer, that are essential for POU5F1 transcription in hESCs. Unexpectedly, we also discovered a new class of enhancers that contribute to POU5F1 transcription in an unusual way: Disruption of such sequences led to a temporary loss of POU5F1 transcription that is fully restored after a few rounds of cell division. These results demonstrate the utility of high-throughput screening for functional characterization of noncoding DNA and reveal a previously unrecognized layer of gene regulation in human cells.

Indexed as

CRISPR-Cas SystemsGene TargetingGenetic TestingPhenotypeCell LineEnhancer Elements, GeneticGene Expression RegulationGenome, HumanHigh-Throughput Screening AssaysHumansOctamer Transcription Factor-3Regulatory Sequences, Nucleic AcidSequence DeletionOctamer Transcription Factor-3POU5F1 protein, human

Identifiers

PMID26813977
PMCPMC4772021
OpenAlexW2272131637

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.