Evidence map›Paper›PMID 38760566›Full record

ArticleNature biotechnology2025

Bidirectional epigenetic editing reveals hierarchies in gene regulation.

Naomi M Pacalin, Zachary Steinhart, Quanming Shi, Julia A Belk, Dmytro Dorovskyi, Katerina Kraft, Kevin R Parker, Brian R Shy, Alexander Marson, Howard Y Chang

Abstract read
In one paragraph

Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing 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

29 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Clinical translation of epigenome editing technologies.Current opinion in biomedical engineering · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Enhancer hubs govern chromatin topology and Th17 cell identity.bioRxiv : the preprint server for biology · 2026
    Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. A unified genetic perturbation language for human cellular programming.bioRxiv : the preprint server for biology · 2025
    Article
  19. Article
  20. Gene circuit-based sensors.Fundamental research · 2025
    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

10 authors.

Naomi M PacalinCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-6870-2090
Zachary SteinhartGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Quanming ShiCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Julia A BelkCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-4724-6158
Dmytro DorovskyiGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.
Katerina KraftCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Kevin R ParkerCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA.
Brian R ShyGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9569-3708
Alexander MarsonGladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2734-5776
Howard Y ChangCenter for Personal Dynamic Regulomes, Stanford University, Stanford, CA, USA. howchang@stanford.edu.ORCID http://orcid.org/0000-0002-9459-4393

Funding

Center for Personal Dynamic RegulomesRM1HG007735 · NHGRI · STANFORD UNIVERSITY · PI CHANG, HOWARD Y · 2019 to 2023
$13.8M
Spatial multiomic mapping of gene function with CRISPRoffUM1HG012660 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Luke Gilbert · 2022 to 2026
$8.2M
Graduate Training Program in BiotechnologyT32GM141819 · NIGMS · STANFORD UNIVERSITY · PI Eric Andrew Appel, Fan Yang · 2021 to 2026
$1.9M
Non-viral genome, epigenome, and transcriptome engineering for clinical CAR-T cell manufacturingK08CA273529 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian R Shy · 2022 to 2026
$1.2M
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) K08CA273529Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) L30TR002983Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) T32GM141819Howard Hughes Medical Institute (HHMI) Hanna Gray FellowHoward Hughes Medical Institute (HHMI) NANational Science Foundation (NSF) GRFPNCATS NIH HHS L30 TR002983NCI NIH HHS K08 CA273529NHGRI NIH HHS RM1 HG007735NHGRI NIH HHS UM1 HG012660NIGMS NIH HHS T32 GM141819Scleroderma Research Foundation (SRF) NA
6 · The paper itself

Abstract

CRISPR perturbation methods are limited in their ability to study non-coding elements and genetic interactions. In this study, we developed a system for bidirectional epigenetic editing, called CRISPRai, in which we apply activating (CRISPRa) and repressive (CRISPRi) perturbations to two loci simultaneously in the same cell. We developed CRISPRai Perturb-seq by coupling dual perturbation gRNA detection with single-cell RNA sequencing, enabling study of pooled perturbations in a mixed single-cell population. We applied this platform to study the genetic interaction between two hematopoietic lineage transcription factors, SPI1 and GATA1, and discovered novel characteristics of their co-regulation on downstream target genes, including differences in SPI1 and GATA1 occupancy at genes that are regulated through different modes. We also studied the regulatory landscape of IL2 (interleukin-2) in Jurkat T cells, primary T cells and chimeric antigen receptor (CAR) T cells and elucidated mechanisms of enhancer-mediated IL2 gene regulation. CRISPRai facilitates investigation of context-specific genetic interactions, provides new insights into gene regulation and will enable exploration of non-coding disease-associated variants.

Indexed as

Epigenesis, GeneticGene EditingGene Expression RegulationCRISPR-Cas SystemsEpigenome EditingGATA1 Transcription FactorHumansInterleukin-2Jurkat CellsProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Single-Cell AnalysisT-LymphocytesTrans-ActivatorsGATA1 protein, humanGATA1 Transcription FactorInterleukin-2Proto-Oncogene ProteinsProto-Oncogene Protein Spi-1Trans-Activators

Identifiers

PMID38760566
PMCPMC11569274

What OpenQuestion holds

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Registered trials

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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.