Evidence map›Paper›PMID 41398462›Full record

ArticleNature structural & molecular biology2026

Evolution of promoter-proximal pausing enabled a new layer of transcription control.

Alexandra G Chivu, Brent A Basso, Abderhman Abuhashem, Michelle M Leger, Gilad Barshad, Edward J Rice, Albert C Vill, Wilfred Wong, Shao-Pei Chou, Gopal Chovatiya and 10 more

Abstract read
PubMed Publisher
In one paragraph

Article in Nature structural & molecular biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing 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

17 citing papers in PubMed.

  1. Structural basis for P-TEFb association with BRD4.bioRxiv : the preprint server for biology · 2026
    Article
  2. Article
  3. Article
  4. Promoter proximal pausing of RNA polymerase across evolution.Nature structural & molecular biology · 2026
    Article
  5. Article
  6. Article
  7. Article
  8. Toward structural understanding of eukaryotic transcription elongation.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2025
    Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Alexandra G Chivu *Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0001-8875-3530
Brent A Basso *Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Abderhman AbuhashemDevelopmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-6135-5679
Michelle M LegerInstitute of Evolutionary Biology, CSIC, Universitat Pompeu Fabra, Barcelona, Spain.ORCID http://orcid.org/0000-0001-5500-5480
Gilad BarshadBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0001-7845-7658
Edward J RiceBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Albert C VillDepartment of Molecular Biology & Genetics, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0001-5982-0298
Wilfred WongComputational and Systems Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-1363-5235
Shao-Pei ChouBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Gopal ChovatiyaDepartment of Molecular Biology & Genetics, Cornell University, Ithaca, NY, USA.ORCID http://orcid.org/0000-0002-0993-8877
Rebecca BradyDepartment of Biology, Ithaca College, Ithaca, NY, USA.ORCID http://orcid.org/0009-0000-3245-7855
Jeramiah J SmithDepartment of Biology, University of Kentucky, Lexington, KY, USA.ORCID http://orcid.org/0000-0001-5333-5531
Athula H WikramanayakeDepartment of Biology, University of Miami, Coral Gables, FL, USA.
César Arenas-MenaDepartment of Biology at the College of Staten Island and PhD Programs in Biology and Biochemistry at The Graduate Center, The City University of New York (CUNY), Staten Island, NY, USA.
Ilana L BritoMeinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
Iñaki Ruiz-TrilloInstitute of Evolutionary Biology, CSIC, Universitat Pompeu Fabra, Barcelona, Spain.ORCID http://orcid.org/0000-0001-6547-5304
Anna-Katerina HadjantonakisDevelopmental Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
John T LisDepartment of Molecular Biology & Genetics, Cornell University, Ithaca, NY, USA. jtl10@cornell.edu.ORCID http://orcid.org/0000-0003-1201-9406
James J LewisBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. jjl8@clemson.edu.ORCID http://orcid.org/0000-0002-4170-9118
Charles G DankoBaker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY, USA. dankoc@gmail.com.ORCID http://orcid.org/0000-0002-1999-7125

Funding

Structure, Function, and Dynamics of Macro-molecular Complexes that Execute and Regulate Genome FunctionRM1GM139738 · NIGMS · CORNELL UNIVERSITY · PI Thomas George Wade Graham, Steven Zvi Josefowicz · 2021 to 2026
$14.4M
Mechanisms driving cell fate specification and morphogenesis in the blastocystR01HD094868 · NICHD · SLOAN-KETTERING INST CAN RESEARCH · PI ANNA-KATERINA HADJANTONAKIS · 2018 to 2026
$4.2M
Phenotyping Early Embryonic Lethal Knockout Mice to Identify Essential Genes with Previously Uncharacterized Roles in Pre-implantation Development, Gastrulation, Turning, and PlacentationR01HD086478 · NICHD · SLOAN-KETTERING INST CAN RESEARCH · PI HADJANTONAKIS, ANNA-KATERINA · 2016 to 2020
$3.4M
The gut endoderm: origin, formation and fateR01DK127821 · NIDDK · SLOAN-KETTERING INST CAN RESEARCH · PI ANNA-KATERINA HADJANTONAKIS · 2021 to 2026
$3.4M
Evolution of Chromatin Architecture and Transcriptional Regulation in MammalsR01HG010346 · NHGRI · CORNELL UNIVERSITY · PI DANKO, CHARLES GRAHE, SIEPEL, ADAM CHARLES · 2019 to 2022
$2.7M
Mapping RNA polymerase in tissue samples with ChRO-seq.R01HG009309 · NHGRI · CORNELL UNIVERSITY · PI DANKO, CHARLES GRAHE · 2017 to 2021
$1.9M
High-Resolution Mapping of Bacterial Transcriptional Responses in Human-Associated Microbiota - SupplementR01GM147731 · NIGMS · CORNELL UNIVERSITY · PI BRITO, ILANA LAUREN · 2022 to 2025
$1.4M
Deciphering Regulatory Syntax: The Interplay of Core Promoter and Transcription Factor Motifs in Gene TranscriptionR01GM166347 · NIGMS · CORNELL UNIVERSITY · PI Charles Grahe Danko · 2026 to 2026
$483k
Dissecting the Role of RNA Pol II Pausing in Early Mammalian DevelopmentF30HD103398 · NICHD · WEILL MEDICAL COLL OF CORNELL UNIV · PI ABUHASHEM, ABDERHMAN ANEES · 2021 to 2024
$178k
NHGRI NIH HHS R01 HG009309NHGRI NIH HHS R01 HG010346NICHD NIH HHS F30 HD103398NICHD NIH HHS R01 HD086478NICHD NIH HHS R01 HD094868NIDDK NIH HHS R01 DK127821NIGMS NIH HHS R01 GM147731NIGMS NIH HHS R01 GM166347NIGMS NIH HHS RM1 GM139738
6 · The paper itself

Abstract

Promoter-proximal pausing of RNA polymerase (Pol) II is a key regulatory step during transcription. Despite the central role of pausing in gene regulation, we do not understand the evolutionary processes that led to the emergence of Pol II pausing or its transition to a rate-limiting step actively controlled by transcription factors. Here, we analyzed transcription in species across the tree of life. Unicellular eukaryotes display an accumulation of Pol II near transcription start sites, which we propose transitioned to the longer-lived, focused pause observed in metazoans. This transition coincided with the evolution of new subunits in the negative elongation factor (NELF) and 7SK complexes. Depletion of NELF in mammals shifted the promoter-proximal buildup of Pol II from the pause site into the early gene body and compromised transcriptional activation for a set of heat-shock genes. Our work details the evolutionary history of Pol II pausing and sheds light on how new transcriptional regulatory mechanisms evolve.

Indexed as

Evolution, MolecularGene Expression RegulationPromoter Regions, GeneticRNA Polymerase IITranscription, GeneticAnimalsHumansTranscription FactorsTranscription Initiation Sitenegative elongation factorRNA Polymerase IITranscription Factors

Identifiers

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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.