Evidence map›Paper›PMID 39905017›Full record

ArticleNature communications2025

Multi-locus CRISPRi targeting with a single truncated guide RNA.

Molly M Moore, Siddarth Wekhande, Robbyn Issner, Alejandro Collins, Anna J Cruz, Yanjing V Liu, Nauman Javed, Salvador Casaní-Galdón, Jason D Buenrostro, Charles B Epstein and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Crosstalk BetweenCancers · 2026
    Review
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

15 authors.

Molly M Moore *Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7833-0769
Siddarth Wekhande *Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0009-0008-7539-8718
Robbyn IssnerGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Alejandro CollinsGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0009-0009-1975-8376
Anna J CruzGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-4517-179X
Yanjing V LiuGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nauman JavedGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Salvador Casaní-GaldónGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8714-3001
Jason D BuenrostroGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9958-3987
Charles B EpsteinGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8358-8345
Eugenio MatteiGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-8889-658X
John G DoenchGenetic Perturbation Platform, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-3707-9889
Bradley E BernsteinGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5726-6278
Noam ShoreshGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5482-5046
Fadi J NajmGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. fadinajm@broadinstitute.org.ORCID http://orcid.org/0009-0005-8515-3763

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

A critical goal in functional genomics is evaluating which non-coding elements contribute to gene expression, cellular function, and disease. Functional characterization remains a challenge due to the abundance and complexity of candidate elements. Here, we develop a CRISPRi-based approach for multi-locus screening of putative transcription factor binding sites with a single truncated guide. A truncated guide with hundreds of sequence match sites can reliably disrupt enhancer activity, which expands the targeting scope of CRISPRi while maintaining repressive efficacy. We screen over 13,000 possible CTCF binding sites with 24 guides at 10 nucleotides in spacer length. These truncated guides direct CRISPRi-mediated deposition of repressive H3K9me3 marks and disrupt transcription factor binding at most sequence match target sites. This approach can be a valuable screening step for testing transcription factor binding motifs or other repeated genomic sequences and is easily implemented with existing tools.

Indexed as

CRISPR-Cas SystemsRNA, Guide, CRISPR-Cas SystemsBinding SitesCCCTC-Binding FactorEnhancer Elements, GeneticGene EditingHistonesHumansTranscription FactorsCCCTC-Binding FactorHistonesRNA, Guide, CRISPR-Cas SystemsTranscription Factors

Identifiers

PMID39905017
PMCPMC11794626

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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 Socratic graph.