Evidence map›Paper›PMID 38769457›Full record

ArticleNature genetics2024

Comparative cofactor screens show the influence of transactivation domains and core promoters on the mechanisms of transcription.

Charles C Bell, Jesse J Balic, Laure Talarmain, Andrea Gillespie, Laura Scolamiero, Enid Y N Lam, Ching-Seng Ang, Geoffrey J Faulkner, Omer Gilan, Mark A Dawson

Abstract read
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In one paragraph

Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing 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

13 citing papers in PubMed.

  1. Review
  2. Article
  3. KMT2C and KMT2D amplify GRHL2-driven enhancer activation.bioRxiv : the preprint server for biology · 2026
    Article
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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

10 authors.

Charles C BellCancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. charles.bell@petermac.org.ORCID http://orcid.org/0000-0003-2194-8311
Jesse J Balic *Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Laure Talarmain *Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Andrea GillespieCancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Laura ScolamieroCancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Enid Y N LamCancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0001-5843-7836
Ching-Seng AngBio21 Mass Spectrometry and Proteomics Facility, The University of Melbourne, Parkville, Victoria, Australia.
Geoffrey J FaulknerMater Research Institute, University of Queensland, TRI Building, Woolloongabba, Queensland, Australia.ORCID http://orcid.org/0000-0001-5769-4494
Omer GilanCancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.ORCID http://orcid.org/0000-0003-4156-2619
Mark A DawsonCancer Research Division, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. mark.dawson@petermac.org.ORCID http://orcid.org/0000-0002-5464-5029

Funding

Cancer Council Victoria 200603Department of Education and Training | Australian Research Council (ARC) DP220103927Department of Health | National Health and Medical Research Council (NHMRC) 1196749Howard Hughes Medical Institute (HHMI) 55008729
6 · The paper itself

Abstract

Eukaryotic transcription factors (TFs) activate gene expression by recruiting cofactors to promoters. However, the relationships between TFs, promoters and their associated cofactors remain poorly understood. Here we combine GAL4-transactivation assays with comparative CRISPR-Cas9 screens to identify the cofactors used by nine different TFs and core promoters in human cells. Using this dataset, we associate TFs with cofactors, classify cofactors as ubiquitous or specific and discover transcriptional co-dependencies. Through a reductionistic, comparative approach, we demonstrate that TFs do not display discrete mechanisms of activation. Instead, each TF depends on a unique combination of cofactors, which influences distinct steps in transcription. By contrast, the influence of core promoters appears relatively discrete. Different promoter classes are constrained by either initiation or pause-release, which influences their dynamic range and compatibility with cofactors. Overall, our comparative cofactor screens characterize the interplay between TFs, cofactors and core promoters, identifying general principles by which they influence transcription.

Indexed as

Promoter Regions, GeneticTranscriptional ActivationTranscription FactorsCRISPR-Cas SystemsGene Expression RegulationHumansTranscription, GeneticTranscription Factors

Identifiers

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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.