Evidence map›Paper›PMID 36503705›Full record

ArticleeLife2022

Predictive modeling reveals that higher-order cooperativity drives transcriptional repression in a synthetic developmental enhancer.

Yang Joon Kim, Kaitlin Rhee, Jonathan Liu, Selene Jeammet, Meghan A Turner, Stephen J Small, Hernan G Garcia

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.1field-weighted citation impact, top 12% of its field
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

15 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Post-transcriptional checkpoints in autoimmunity.Nature reviews. Rheumatology · 2023
    Review
  12. Article
  13. Competing constraints shape the nonequilibrium limits of cellular decision-making.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  14. Article
  15. Article
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

7 authors at 5 institutions in 2 countries.

Yang Joon KimChan Zuckerberg Biohub, San Francisco, United States.ORCID 0000-0003-1742-5657
Kaitlin RheeDepartment of Chemical Biology, University of California, Berkeley, Berkeley, United States.
Jonathan LiuDepartment of Physics, University of California, Berkeley, Berkeley, United States.
Selene JeammetDepartment of Biology, Ecole Polytechnique, Paris, France.
Meghan A TurnerBiophysics Graduate Group, University of California, Berkeley, Berkeley, United States.
Stephen J SmallDepartment of Biology, New York University, New York, United States.
Hernan G GarciaChan Zuckerberg Biohub, San Francisco, United States.ORCID 0000-0002-5212-3649
University of California, Berkeley · USChan Zuckerberg Initiative (United States) · USÉcole Polytechnique · FRNew York University · USQB3 · US

Funding

Lighting Up the Central Dogma in Embryonic DevelopmentDP2HD094655 · NICHD · UNIVERSITY OF CALIFORNIA BERKELEY · PI GARCIA, HERNAN GUSTAVO · 2017 to 2017
$2.4M
Predictive understanding of the temporal control of transcription in Drosophila developmentR01GM139913 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI GARCIA, HERNAN GUSTAVO · 2021 to 2024
$1.2M
Is Calcium the Gear Shift? The Role of Calcium-Mediated TgMyoA Phosphorylation in Toxoplasma Gondii MotilityF31AI145214 · NIAID · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI STADLER, RACHEL · 2020 to 2022
$77k
NIAID NIH HHS F31 AI145214NICHD NIH HHS DP2 HD094655NIGMS NIH HHS R01 GM139913
6 · The paper itself

Abstract

A challenge in quantitative biology is to predict output patterns of gene expression from knowledge of input transcription factor patterns and from the arrangement of binding sites for these transcription factors on regulatory DNA. We tested whether widespread thermodynamic models could be used to infer parameters describing simple regulatory architectures that inform parameter-free predictions of more complex enhancers in the context of transcriptional repression by Runt in the early fruit fly embryo. By modulating the number and placement of Runt binding sites within an enhancer, and quantifying the resulting transcriptional activity using live imaging, we discovered that thermodynamic models call for higher-order cooperativity between multiple molecular players. This higher-order cooperativity captures the combinatorial complexity underlying eukaryotic transcriptional regulation and cannot be determined from simpler regulatory architectures, highlighting the challenges in reaching a predictive understanding of transcriptional regulation in eukaryotes and calling for approaches that quantitatively dissect their molecular nature.

Indexed as

Drosophila melanogasterDrosophila ProteinsAnimalsDrosophilaEnhancer Elements, GeneticGene ExpressionGene Expression Regulation, DevelopmentalTranscription FactorsDrosophila ProteinsTranscription FactorsD. melanogasterDrosophila melanogasterlive imaging of transcriptionphysics of living systemsrunt repressorsynthetic enhancersthermodynamic modelstranscriptional repression

Identifiers

PMID36503705
PMCPMC9836395
OpenAlexW4312095802

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.