Evidence map›Paper›PMID 27708104›Full record

ArticleScience (New York, N.Y.)2016

High-resolution interrogation of functional elements in the noncoding genome.

Neville E Sanjana, Jason Wright, Kaijie Zheng, Ophir Shalem, Pierre Fontanillas, Julia Joung, Christine Cheng, Aviv Regev, Feng Zhang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science (New York, N.Y.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
168citing papers in PubMed, 1 pooled it
–field-weighted citation impact, top 84% 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

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

  1. Pooled it
  2. Tuning epigenetics to enhance cancer virotherapy.Acta pharmaceutica Sinica. B · 2026
    Review
  3. Article
  4. Synthetic Regulatory Genomics.Annual review of genomics and human genetics · 2026
    Review
  5. Article
  6. Scaling perturbations: beyond genome-scale CRISPR screens.bioRxiv : the preprint server for biology · 2026
    Article
  7. Article
  8. Human Synthetic Biology and Programmable Gene Regulation Control.Annual review of genomics and human genetics · 2025
    Review
  9. CRISPR-based functional genomics tools in vertebrate models.Experimental & molecular medicine · 2025
    Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Review
  19. Review
  20. Review

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 1 country.

Neville E SanjanaBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. nsanjana@nygenome.org zhang@broadinstitute.org.
Jason WrightBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Kaijie ZhengBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Ophir ShalemBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Pierre FontanillasBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
Julia JoungBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Christine ChengBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, David H. Koch Institute of Integrative Cancer Biology, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Aviv RegevBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. Howard Hughes Medical Institute, David H. Koch Institute of Integrative Cancer Biology, Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Feng ZhangBroad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA. McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. nsanjana@nygenome.org zhang@broadinstitute.org.
Broad Institute · USMassachusetts Institute of Technology · USHoward Hughes Medical Institute · USMcGovern Institute for Brain Research · 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
Genome engineering tools for functional screening of non-coding elementsK99HG008171 · NHGRI · BROAD INSTITUTE, INC. · PI SANJANA, NEVILLE · 2015 to 2016
$125k
NHGRI NIH HHS K99 HG008171NHGRI 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

The noncoding genome affects gene regulation and disease, yet we lack tools for rapid identification and manipulation of noncoding elements. We developed a CRISPR screen using ~18,000 single guide RNAs targeting >700 kilobases surrounding the genes NF1, NF2, and CUL3, which are involved in BRAF inhibitor resistance in melanoma. We find that noncoding locations that modulate drug resistance also harbor predictive hallmarks of noncoding function. With a subset of regions at the CUL3 locus, we demonstrate that engineered mutations alter transcription factor occupancy and long-range and local epigenetic environments, implicating these sites in gene regulation and chemotherapeutic resistance. Through our expansion of the potential of pooled CRISPR screens, we provide tools for genomic discovery and for elucidating biologically relevant mechanisms of gene regulation.

Indexed as

Gene Expression RegulationGenome, HumanAntineoplastic AgentsBacterial ProteinsClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated Protein 9Cullin ProteinsDrug Resistance, NeoplasmEndonucleasesEnhancer Elements, GeneticGene Expression Regulation, NeoplasticGenes, Neurofibromatosis 1Genes, Neurofibromatosis 2Genetic LociGenomicsHumansAntineoplastic AgentsBacterial ProteinsBRAF protein, humanCas9 endonuclease Streptococcus pyogenesCRISPR-Associated Protein 9CUL3 protein, humanCullin ProteinsEndonucleasesIndolesProto-Oncogene Proteins B-rafRNA, Guide, CRISPR-Cas SystemsSulfonamidesVemurafenib

Identifiers

PMID27708104
PMCPMC5144102
OpenAlexW2787240693

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.