Evidence map›Paper›PMID 31235883›Full record

ArticleNature methods2019

LADL: light-activated dynamic looping for endogenous gene expression control.

Ji Hun Kim, Mayuri Rege, Jacqueline Valeri, Margaret C Dunagin, Aryeh Metzger, Katelyn R Titus, Thomas G Gilgenast, Wanfeng Gong, Jonathan A Beagan, Arjun Raj and 1 more

Open access · greenAbstract read
In one paragraph

Article in Nature methods, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.

0numbers the graph read from it
0cells of the map it votes in
87citing papers in PubMed
7.7field-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

87 citing papers in PubMed, 136 citations in OpenAlex.

  1. 3D Genome Engineering Using CRISPR/dCas Systems.International journal of molecular sciences · 2026
    Review
  2. Advances and clinical potential of epigenome editing.Cellular and molecular life sciences : CMLS · 2026
    Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

27 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 3 countries.

Ji Hun KimDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Mayuri RegeDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Jacqueline ValeriDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Margaret C DunaginDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Aryeh MetzgerDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Katelyn R TitusDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Thomas G GilgenastDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Wanfeng GongDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Jonathan A BeaganDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.
Arjun RajDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-2915-6960
Jennifer E Phillips-CreminsDepartment of Bioengineering, University of Pennsylvania, Philadelphia, PA, USA. jcremins@seas.upenn.edu.ORCID http://orcid.org/0000-0002-4702-0450
University of Pennsylvania · USBioengineering Center · RUUniversitat Autònoma de Barcelona · ES

Funding

Engineering and visualizing genome folding at high spatiotemporal resolutionU01HL129998 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI BLOBEL, GERD A, PHILLIPS-CREMINS, JENNIFER ELIZABETH · 2015 to 2019
$4.2M
Engineering 3-D Epigenome Topology with LightDP2MH110247 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI PHILLIPS-CREMINS, JENNIFER ELIZABETH · 2015 to 2015
$2.4M
NHLBI NIH HHS U01 HL129998NIMH NIH HHS DP2 MH110247
6 · The paper itself

Abstract

Mammalian genomes are folded into tens of thousands of long-range looping interactions. The cause-and-effect relationship between looping and genome function is poorly understood, and the extent to which loops are dynamic on short time scales remains an unanswered question. Here, we engineer a new class of synthetic architectural proteins for directed rearrangement of the three-dimensional genome using blue light. We target our light-activated-dynamic-looping (LADL) system to two genomic anchors with CRISPR guide RNAs and induce their spatial colocalization via light-induced heterodimerization of cryptochrome 2 and a dCas9-CIBN fusion protein. We apply LADL to redirect a stretch enhancer (SE) away from its endogenous Klf4 target gene and to the Zfp462 promoter. Using single-molecule RNA-FISH, we demonstrate that de novo formation of the Zfp462-SE loop correlates with a modest increase in Zfp462 expression. LADL facilitates colocalization of genomic loci without exogenous chemical cofactors and will enable future efforts to engineer reversible and oscillatory loops on short time scales.

Indexed as

Gene Expression RegulationProtein EngineeringAnimalsCarrier ProteinsCells, CulturedDNA-Binding ProteinsKruppel-Like Factor 4Kruppel-Like Transcription FactorsLightMaleMiceNerve Tissue ProteinsPromoter Regions, GeneticRNA, Guide, CRISPR-Cas SystemsCarrier ProteinsDNA-Binding ProteinsKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsNerve Tissue ProteinsRNA, Guide, CRISPR-Cas SystemsZfp462 protein, mouse

Identifiers

PMID31235883
PMCPMC6599567
OpenAlexW2949539957

What OpenQuestion holds

Textmetadata
LicenceTDM
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.