Evidence map›Paper›PMID 40998781›Full record

ArticleNature communications2025

Disease-linked regulatory DNA variants and homeostatic transcription factors in epidermis.

Douglas F Porter, Robin M Meyers, Weili Miao, David L Reynolds, Audrey W Hong, Xue Yang, Suhas Srinivasan, Smarajit Mondal, Zurab Siprashvili, Tania Fabo and 20 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. The adhesion GPCR ADGRL2 engages Gα13 to enable epidermal differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

30 authors.

Douglas F Porter *Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA. dfporter@stanford.edu.
Robin M Meyers *Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Weili Miao *Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-7487-8962
David L Reynolds *Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Audrey W HongProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Xue YangProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Suhas SrinivasanProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8309-9648
Smarajit MondalProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-2883-2728
Zurab SiprashviliProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Tania FaboDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-8987-0672
Ronghao ZhouDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Tri NguyenDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.
Luca DucoliProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1731-9029
Jordan M MeyersProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Duy T NguyenProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Lisa A KoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3732-0580
Laura N KellmanProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-1073-8936
Ibtihal ElfakiProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Margaret GuoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Mårten Cg WingeProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Leandra V JackraziProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Vanessa Lopez-PajaresProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8538-344X
Betty B LiuDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-1655-7164
Yuanhao QuProgram in Cancer Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-7574-259X
Imani E PorterDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-0043-2658
Samuel H KimProgram in Cancer Biology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-8353-6190
Gyuhyeon KimProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Shiying TaoProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA.
Jesse M EngreitzDepartment of Genetics, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-5754-1719
Paul A KhavariProgram in Epithelial Biology, Stanford University School of Medicine, Stanford, CA, USA. khavari@stanford.edu.ORCID http://orcid.org/0000-0003-0098-4989

Funding

The UCSC Genome BrowserU24HG002371 · NHGRI · UNIVERSITY OF CALIFORNIA SANTA CRUZ · PI Maximilian Haeussler · 2022 to 2026
$17.6M
REGULATORS OF EPIDERMAL GENE EXPRESSIONR01AR045192 · NIAMS · STANFORD UNIVERSITY · PI PAUL KHAVARI · 1999 to 2026
$9.9M
Regulatory Variants in HUMAN SKIN DISEASESR01AR076965 · NIAMS · STANFORD UNIVERSITY · PI PAUL KHAVARI · 2020 to 2026
$3.6M
Atlas of Regulatory Variants in Diseases (ARVID)U24HG010856 · NHGRI · STANFORD UNIVERSITY · PI KHAVARI, PAUL · 2020 to 2024
$3.3M
REGULATION OF SKIN HOMEOSTASIS BY RNA-BINDING PROTEINSK01AR082351 · NIAMS · STANFORD UNIVERSITY · PI PORTER, DOUGLAS F · 2023 to 2025
$369k
GLUCOSE BINDS RBPs TO REGULATE EPIDERMAL HOMEOSTASISK01AR084077 · NIAMS · STANFORD UNIVERSITY · PI Weili Miao · 2024 to 2026
$338k
BLRD VA I01 BX001409NHGRI NIH HHS U24 HG002371NHGRI NIH HHS U24 HG010856NIAMS NIH HHS K01 AR082351NIAMS NIH HHS K01 AR084077NIAMS NIH HHS R01 AR045192NIAMS NIH HHS R01 AR076965U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) HG010856U.S. Department of Health & Human Services | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) AR076965, AR045192
6 · The paper itself

Abstract

Identifying noncoding single nucleotide variants (SNVs) in regulatory DNA linked to polygenic disease risk, the transcription factors (TFs) they bind, and the genes they dysregulate is a goal in polygenic disease research. Here, we use massively parallel reporter analysis of 3451 SNVs linked to risk for polygenic skin diseases with disrupted epidermal homeostasis to identify 355 differentially active SNVs (daSNVs). daSNV target gene analysis, combined with daSNV editing, underscored dysregulated epidermal differentiation as a shared pathomechanism. CRISPR knockout screens of 1772 human TFs revealed 123 TFs essential for epidermal homeostasis, highlighting ZNF217 and CXXC1. Population sampling CUT&RUN of 27 homeostatic TFs identified allele-specific DNA binding (ASB) differences at daSNVs enriched near epidermal homeostasis and monogenic skin disease genes, with notable representation of SP/KLF and AP-1/2 TFs. High TF-occupancy promoters were "buffered" against ASB. This resource implicates dysregulated binding of specific homeostatic TF families in risk for diverse polygenic skin diseases.

Indexed as

DNAEpidermisPolymorphism, Single NucleotideSkin DiseasesTranscription FactorsAllelesCRISPR-Cas SystemsGenetic Predisposition to DiseaseHomeostasisHumansMultifactorial InheritancePromoter Regions, GeneticDNATranscription Factors

Identifiers

PMID40998781
PMCPMC12462481

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.