Evidence map›Paper›PMID 32958950›Full record

ArticleNature genetics2020

Transcription imparts architecture, function and logic to enhancer units.

Nathaniel D Tippens, Jin Liang, Alden King-Yung Leung, Shayne D Wierbowski, Abdullah Ozer, James G Booth, John T Lis, Haiyuan Yu

Abstract read
In one paragraph

Article in Nature genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.

0numbers the graph read from it
0cells of the map it votes in
69citing 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

69 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Developmental expression of the skeletal muscle determination gene,bioRxiv : the preprint server for biology · 2026
    Article
  6. Locus-Scale Massively Parallel Reporter Assays.bioRxiv : the preprint server for biology · 2026
    Article
  7. Article
  8. Article
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  11. Article
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  15. Article
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article

9 more citing papers are in PubMed but not listed here.

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

8 authors.

Nathaniel D Tippens *Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0003-4377-8691
Jin Liang *Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
Alden King-Yung LeungWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
Shayne D WierbowskiWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0002-2595-2011
Abdullah OzerDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
James G BoothDepartment of Statistics and Data Science, Cornell University, Ithaca, NY, USA.
John T LisDepartment of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA. johnlis@cornell.edu.ORCID http://orcid.org/0000-0003-1201-9406
Haiyuan YuWeill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA. haiyuan.yu@cornell.edu.ORCID http://orcid.org/0000-0001-7597-6049

Funding

COORDINATE GENE REGULATION IN ANIMAL CELLSR01GM025232 · NIGMS · CORNELL UNIVERSITY ITHACA · PI LIS, JOHN T · 1985 to 2020
$8.4M
High-throughput functional characterization of human enhancersUM1HG009393 · NHGRI · CORNELL UNIVERSITY · PI LIS, JOHN T, YU, HAIYUAN · 2017 to 2021
$4.1M
Tri-Institutional PhD Program in Computational Biology & MedicineT32GM132083 · NIGMS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Doron Betel, Iman Hajirasouliha · 2020 to 2026
$3.6M
Integrated high-throughput functional assays to identify ulcerative colitis causal risk variantsR01DK115398 · NIDDK · CORNELL UNIVERSITY · PI KLEIN, ROBERT J., YU, HAIYUAN · 2018 to 2022
$3.3M
COORDINATE GENE REGULATION IN ANIMAL CELLSR37GM025232 · NIGMS · CORNELL UNIVERSITY ITHACA · PI LIS, JOHN THOMAS · 1995 to 2004
$2.5M
Prioritizing rare variants associated with cancer using non-coding annotationR01HG008126 · NHGRI · YALE UNIVERSITY · PI GERSTEIN, MARK BENDER · 2016 to 2018
$2.4M
Research and Career Training in Vertebrate Developmental GenomicsT32HD057854 · NICHD · CORNELL UNIVERSITY · PI SCHIMENTI, JOHN C · 2010 to 2020
$1.3M
NHGRI NIH HHS R01 HG008126NHGRI NIH HHS UM1 HG009393NICHD NIH HHS T32 HD057854NIDDK NIH HHS R01 DK115398NIGMS NIH HHS R01 GM025232NIGMS NIH HHS R37 GM025232NIGMS NIH HHS T32 GM132083
6 · The paper itself

Abstract

Distal enhancers play pivotal roles in development and disease yet remain one of the least understood regulatory elements. We used massively parallel reporter assays to perform functional comparisons of two leading enhancer models and find that gene-distal transcription start sites are robust predictors of active enhancers with higher resolution than histone modifications. We show that active enhancer units are precisely delineated by active transcription start sites, validate that these boundaries are sufficient for capturing enhancer function, and confirm that core promoter sequences are necessary for this activity. We assay adjacent enhancers and find that their joint activity is often driven by the stronger unit within the cluster. Finally, we validate these results through functional dissection of a distal enhancer cluster using CRISPR-Cas9 deletions. In summary, definition of high-resolution enhancer boundaries enables deconvolution of complex regulatory loci into modular units.

Indexed as

Transcription, GeneticTranscription Initiation SiteCell LineClustered Regularly Interspaced Short Palindromic RepeatsEnhancer Elements, GeneticHistone CodeHumansPromoter Regions, GeneticProtein Processing, Post-TranslationalTranscription Initiation, Genetic

Identifiers

PMID32958950
PMCPMC7541647

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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.