Evidence map›Paper›PMID 40935921›Full record

ArticleNature methods2025

Coupling CRISPR scanning with targeted chromatin accessibility profiling using a double-stranded DNA deaminase.

Heejin Roh, Simon P Shen, Yan Hu, Hui Si Kwok, Allison P Siegenfeld, Ceejay Lee, Marcanthony U Zepeda, Chun-Jie Guo, Shelby A Roseman, Caroline Comenho and 3 more

Abstract read
In one paragraph

Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

  1. Review
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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

13 authors.

Heejin Roh *Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5100-689X
Simon P Shen *Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2310-7831
Yan Hu *Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Hui Si KwokDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Allison P SiegenfeldDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-8599-577X
Ceejay LeeDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Marcanthony U ZepedaDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Chun-Jie GuoGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0009-0001-7421-586X
Shelby A RosemanDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA.
Caroline ComenhoGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2955-1984
Vijay G SankaranGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-0044-443X
Jason D BuenrostroGene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9958-3987
Brian B LiauDepartment of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA. liau@chemistry.harvard.edu.ORCID http://orcid.org/0000-0002-2985-462X

Funding

Systematic Genetic Dissection of Human ErythropoiesisR01DK103794 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI Vijay Ganesh Sankaran · 2014 to 2026
$5.9M
Integrating Chemical Genetic Approaches with Precision Genome EditingR35GM153476 · NIGMS · HARVARD UNIVERSITY · PI Brian Liau · 2024 to 2026
$1.2M
Investigating the functional role of a degron in ASXL1 in hematopoiesis and diseaseF31HL174076 · NHLBI · HARVARD UNIVERSITY · PI SHEN, SIMON P · 2024 to 2025
$77k
National Science Foundation (NSF) DGE1745303NHLBI NIH HHS F31 HL174076NIDDK NIH HHS R01 DK103794NIGMS NIH HHS R35 GM153476U.S. Department of Health & Human Services | National Institutes of Health (NIH) F31HL174076U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01DK103794U.S. Department of Health & Human Services | National Institutes of Health (NIH) R35GM153476
6 · The paper itself

Abstract

Genome editing enables sequence-function profiling of endogenous cis-regulatory elements, driving understanding of their mechanisms. However, these approaches lack direct, scalable readouts of chromatin accessibility across long single-molecule chromatin fibers. Here we leverage double-stranded DNA cytidine deaminases to profile chromatin accessibility at endogenous loci of interest through targeted PCR and long-read sequencing, a method we term targeted deaminase-accessible chromatin sequencing (TDAC-seq). With high sequence coverage at targeted loci, TDAC-seq can be integrated with CRISPR perturbations to link genetic edits and their effects on chromatin accessibility on the same single chromatin fiber at single-nucleotide resolution. We employed TDAC-seq to parse CRISPR edits that activate fetal hemoglobin in human CD34

Indexed as

ChromatinClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Cas SystemsCytidine DeaminaseGene EditingHematopoietic Stem CellsHumansChromatinCytidine Deaminase

Identifiers

PMID40935921
PMCPMC12825449

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.