Evidence map›Paper›PMID 25259920›Full record

ArticleCell2014

Evolution of DNA specificity in a transcription factor family produced a new gene regulatory module.

Alesia N McKeown, Jamie T Bridgham, Dave W Anderson, Michael N Murphy, Eric A Ortlund, Joseph W Thornton

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed
5.3field-weighted citation impact, top 3% 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

70 citing papers in PubMed, 122 citations in OpenAlex.

  1. Review
  2. Epistatic drift in protein evolution.Current opinion in genetics & development · 2025
    Review
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  8. A GATA factor radiation inbioRxiv : the preprint server for biology · 2025
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Topiary: Pruning the manual labor from ancestral sequence reconstruction.Protein science : a publication of the Protein Society · 2023
    Article

10 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

6 authors at 2 institutions in 1 country.

Alesia N McKeownInstitute of Ecology and Evolution, University of Oregon, Eugene, OR 97403, USA.
Jamie T BridghamInstitute of Ecology and Evolution, University of Oregon, Eugene, OR 97403, USA.
Dave W AndersonInstitute of Ecology and Evolution, University of Oregon, Eugene, OR 97403, USA.
Michael N MurphyDepartment of Biochemistry, Emory University, Atlanta, GA 30322, USA.
Eric A OrtlundDepartment of Biochemistry, Emory University, Atlanta, GA 30322, USA.
Joseph W ThorntonInstitute of Ecology and Evolution, University of Oregon, Eugene, OR 97403, USA; Department of Ecology and Evolution and Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. Electronic address: joet1@uchicago.edu.
University of Oregon · USEmory University · US

Funding

MOLECULAR BIOLOGY AND BIOPHYSICST32GM007759 · NIGMS · UNIVERSITY OF OREGON · PI NOLEN, BRADLEY J · 1985 to 2021
$8.5M
Mechanisms for the evolution of novel DNA specificity in a transcription factor fR01GM104397 · NIGMS · UNIVERSITY OF CHICAGO · PI THORNTON, JOSEPH W · 2013 to 2016
$1.3M
Howard Hughes Medical InstituteNIGMS NIH HHS 5-T32-GM-7759-33NIGMS NIH HHS R01 GM104397NIGMS NIH HHS R01-GM104397NIGMS NIH HHS T32 GM007759
6 · The paper itself

Abstract

Complex gene regulatory networks require transcription factors (TFs) to bind distinct DNA sequences. To understand how novel TF specificity evolves, we combined phylogenetic, biochemical, and biophysical approaches to interrogate how DNA recognition diversified in the steroid hormone receptor (SR) family. After duplication of the ancestral SR, three mutations in one copy radically weakened binding to the ancestral estrogen response element (ERE) and improved binding to a new set of DNA sequences (steroid response elements, SREs). They did so by establishing unfavorable interactions with ERE and abolishing unfavorable interactions with SRE; also required were numerous permissive substitutions, which nonspecifically improved cooperativity and affinity of DNA binding. Our findings indicate that negative determinants of binding play key roles in TFs' DNA selectivity and-with our prior work on the evolution of SR ligand specificity during the same interval-show how a specific new gene regulatory module evolved without interfering with the integrity of the ancestral module.

Indexed as

Evolution, MolecularGene Regulatory NetworksResponse ElementsAnimalsCrystallography, X-RayHumansModels, MolecularMolecular Sequence DataPhylogenyReceptors, SteroidReceptors, Steroid

Identifiers

PMID25259920
PMCPMC4447315
OpenAlexW2152005166

What OpenQuestion holds

Textmetadata
LicenceTDM
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.