Evidence map›Paper›PMID 28792927›Full record

ArticleNature2017

Genome-scale activation screen identifies a lncRNA locus regulating a gene neighbourhood.

Julia Joung, Jesse M Engreitz, Silvana Konermann, Omar O Abudayyeh, Vanessa K Verdine, Francois Aguet, Jonathan S Gootenberg, Neville E Sanjana, Jason B Wright, Charles P Fulco and 5 more

Erratum issuedAbstract read
In one paragraph

Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 267 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
267citing papers in PubMed, 1 pooled it
18.5field-weighted citation impact, top 1% 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

267 citing papers in PubMed, 1 synthesis or guideline pooled it, 441 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Tuning epigenetics to enhance cancer virotherapy.Acta pharmaceutica Sinica. B · 2026
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  10. EditingBiomolecules · 2026
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  16. Non-coding RNA · 2025
    Review
  17. Review
  18. Article
  19. Article
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 6 institutions in 1 country.

Julia JoungDepartment of Biological Engineering, MIT, Cambridge, Massachusetts 02139, USA.
Jesse M EngreitzBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Silvana KonermannBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Omar O AbudayyehBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Vanessa K VerdineBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Francois AguetBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Jonathan S GootenbergBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Neville E SanjanaBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Jason B WrightBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Charles P FulcoBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Yuen-Yi TsengBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Charles H YoonDepartment of Surgery, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Jesse S BoehmBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Eric S LanderBroad Institute of MIT and Harvard, Cambridge, Massachusetts 02142, USA.
Feng ZhangDepartment of Biological Engineering, MIT, Cambridge, Massachusetts 02139, USA.
Broad Institute · USMcGovern Institute for Brain Research · USIIT@MIT · USBrigham and Women's Hospital · USCenter for Systems Biology · USHarvard University · US

Funding

Center for Cell CircuitsRM1HG006193 · NHGRI · BROAD INSTITUTE, INC. · PI BLAINEY, PAUL CLARK, HACOHEN, NIR · 2016 to 2020
$14.9M
Massively-parallel functional interrogation of psychiatric geneticsR01MH110049 · NIMH · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2015 to 2019
$5.5M
Probing Neuropsychiatric Diseases Using Targeted Epigenome and Genome EngineeringDP1MH100706 · NIMH · BROAD INSTITUTE, INC. · PI ZHANG, FENG · 2012 to 2016
$4.3M
Genome engineering tools for functional screening of non-coding elementsR00HG008171 · NHGRI · NEW YORK GENOME CENTER · PI SANJANA, NEVILLE · 2016 to 2018
$733k
Identification of mechanisms of diabetes predisposition in the 9p21 locusF32DK096822 · NIDDK · BROAD INSTITUTE, INC. · PI WRIGHT, JASON BOKE · 2012 to 2014
$170k
Howard Hughes Medical InstituteNHGRI NIH HHS R00 HG008171NHGRI NIH HHS RM1 HG006193NIDDK NIH HHS F32 DK096822NIMH NIH HHS DP1 MH100706NIMH NIH HHS R01 MH110049
6 · The paper itself

Abstract

Mammalian genomes contain thousands of loci that transcribe long noncoding RNAs (lncRNAs), some of which are known to carry out critical roles in diverse cellular processes through a variety of mechanisms. Although some lncRNA loci encode RNAs that act non-locally (in trans), there is emerging evidence that many lncRNA loci act locally (in cis) to regulate the expression of nearby genes-for example, through functions of the lncRNA promoter, transcription, or transcript itself. Despite their potentially important roles, it remains challenging to identify functional lncRNA loci and distinguish among these and other mechanisms. Here, to address these challenges, we developed a genome-scale CRISPR-Cas9 activation screen that targets more than 10,000 lncRNA transcriptional start sites to identify noncoding loci that influence a phenotype of interest. We found 11 lncRNA loci that, upon recruitment of an activator, mediate resistance to BRAF inhibitors in human melanoma cells. Most candidate loci appear to regulate nearby genes. Detailed analysis of one candidate, termed EMICERI, revealed that its transcriptional activation resulted in dosage-dependent activation of four neighbouring protein-coding genes, one of which confers the resistance phenotype. Our screening and characterization approach provides a CRISPR toolkit with which to systematically discover the functions of noncoding loci and elucidate their diverse roles in gene regulation and cellular function.

Indexed as

Cell Line, TumorCRISPR-Cas SystemsDrug Resistance, NeoplasmGenetic LociGenome, HumanHippo Signaling PathwayHumansIndolesMelanomaMicrotubule-Associated ProteinsPhenotypePromoter Regions, GeneticProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene Proteins B-rafRNA, Long NoncodingBRAF protein, humanIndolesMicrotubule-Associated ProteinsMOB3B protein, humanProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene Proteins B-rafRNA, Long NoncodingSulfonamidesVemurafenib

Identifiers

PMID28792927
PMCPMC5706657
OpenAlexW2744996861

What OpenQuestion holds

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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.