Evidence map›Paper›PMID 41881989›Full record

ArticleNature communications2026

CRISPR tiling deletion screens reveal functional enhancers and allelic compensation effects (ACE) on SIN3A transcription.

Xingjie Ren, Lina Zheng, Yuxi Liu, Lenka Maliskova, Tsz Wai Tam, Yifan Sun, Hongjiang Liu, Xiekui Cui, Jerry Lee, Maya Asami Takagi and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. The Encyclopedia of DNA Elements.bioRxiv : the preprint server for biology · 2026
    Article
  3. Haplotype editing with CRISPR-Cas9 as a therapeutic approach for dominant-negative missense mutations in NEFL.Molecular therapy : the journal of the American Society of Gene Therapy · 2026
    Article
  4. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Xingjie RenInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Lina ZhengBioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, USA.
Yuxi LiuInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Lenka MaliskovaInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Tsz Wai TamInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Yifan SunInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Hongjiang LiuInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-6600-642X
Xiekui CuiInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Jerry LeeInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Maya Asami TakagiInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA.
Bin LiDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Bing RenDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.
Wei WangBioinformatics and Systems Biology Graduate Program, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4377-5060
Yin ShenInstitute for Human Genetics, University of California, San Francisco, San Francisco, CA, USA. yin.shen@ucsf.edu.ORCID http://orcid.org/0000-0001-9901-5613

Funding

Research BaseP30DK063720 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GERMAN, MICHAEL S · 2003 to 2019
$21.8M
High throughput CRISPR-mediated functional validation of regulatory elementsUM1HG009402 · NHGRI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI REN, BING, SHEN, YIN · 2017 to 2021
$8.4M
U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) UM1HG009402U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) P30DK063720U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD) 1S10OD028511-01U.S. Department of Health & Human Services | NIH | NIH Office of the Director (OD) S101S10OD021822-01
6 · The paper itself

Abstract

Precise transcriptional regulation is critical for cellular function and development, yet the mechanism of this process remains poorly understood for many genes. To gain a deeper understanding of the regulation of neuropsychiatric disease risk genes, we identify a total of 39 functional enhancers for four dosage-sensitive genes, APP, FMR1, MECP2, and SIN3A, using CRISPR tiling deletion screening in human induced pluripotent stem cell (iPSC)-induced excitatory neurons. More importantly, we discover that allelic enhancer deletions at SIN3A could be compensated by increased transcriptional activities from the other intact allele. Such allelic compensation effects (ACE) on transcription are stably maintained during differentiation and, once established, cannot be reversed by ectopic SIN3A expression. Further, ACE at SIN3A occurs through dosage sensing by the promoter. Together, our findings unravel a regulatory compensation mechanism that ensures stable and precise transcriptional output for SIN3A, and potentially other dosage-sensitive genes.

Indexed as

Clustered Regularly Interspaced Short Palindromic RepeatsEnhancer Elements, GeneticRepressor ProteinsTranscription, GeneticAllelesCell DifferentiationCRISPR-Cas SystemsGene Expression RegulationHumansInduced Pluripotent Stem CellsMethyl-CpG-Binding Protein 2NeuronsPromoter Regions, GeneticSin3 Histone Deacetylase and Corepressor ComplexMethyl-CpG-Binding Protein 2Repressor ProteinsSIN3A transcription factorSin3 Histone Deacetylase and Corepressor Complex

Identifiers

PMID41881989
PMCPMC13181091

What OpenQuestion holds

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LicenceCC BY
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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.