Evidence map›Paper›PMID 22080951›Full record

ArticleNature2011

Regulatory evolution through divergence of a phosphoswitch in the transcription factor CEBPB.

Vincent J Lynch, Gemma May, Günter P Wagner

Abstract read
PubMed Publisher
In one paragraph

Article in Nature, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
3.7field-weighted citation impact, top 6% 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

63 citing papers in PubMed, 111 citations in OpenAlex.

  1. Article
  2. Article
  3. Origins of allostery in vertebrate hemoglobin evolution.bioRxiv : the preprint server for biology · 2026
    Article
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  5. Article
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  7. Article
  8. Article
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  10. Article
  11. Article
  12. Functional Bidirectionality of ERV-Derived Long Non-Coding RNAs in Humans.International journal of molecular sciences · 2024
    Review
  13. Pseudo-perplexity in One Fell Swoop for Protein Fitness Estimation.bioRxiv : the preprint server for biology · 2024
    Article
  14. Article
  15. Article
  16. Article
  17. Simple mechanisms for the evolution of protein complexity.Protein science : a publication of the Protein Society · 2022
    Review
  18. Review
  19. Article
  20. Article

3 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

3 authors at 1 institution in 1 country.

Vincent J LynchYale Systems Biology Institute and Department of Ecology and Evolutionary Biology, Yale University, New Haven, Connecticut 06511, USA. vincent.j.lynch@yale.edu
Gemma May
Günter P Wagner
Yale University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

There is an emerging consensus that gene regulation evolves through changes in cis-regulatory elements and transcription factors. Although it is clear how nucleotide substitutions in cis-regulatory elements affect gene expression, it is not clear how amino-acid substitutions in transcription factors influence gene regulation. Here we show that amino-acid changes in the transcription factor CCAAT/enhancer binding protein-β (CEBPB, also known as C/EBP-β) in the stem-lineage of placental mammals changed the way it responds to cyclic AMP/protein kinase A (cAMP/PKA) signalling. By functionally analysing resurrected ancestral proteins, we identify three amino-acid substitutions in an internal regulatory domain of CEBPB that are responsible for the novel function. These amino-acid substitutions reorganize the location of key phosphorylation sites, introducing a new site and removing two ancestral sites, reversing the response of CEBPB to GSK-3β-mediated phosphorylation from repression to activation. We conclude that changing the response of transcription factors to signalling pathways can be an important mechanism of gene regulatory evolution.

Indexed as

Evolution, MolecularGene Expression RegulationAmino Acid SubstitutionAnimalsCCAAT-Enhancer-Binding Protein-betaCyclic AMPCyclic AMP-Dependent Protein KinasesFemaleForkhead Box Protein O1Forkhead Transcription FactorsGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHeLa CellsHumansMammalsModels, MolecularCCAAT-Enhancer-Binding Protein-betaCEBPB protein, humanCyclic AMPCyclic AMP-Dependent Protein KinasesForkhead Box Protein O1Forkhead Transcription FactorsFOXO1 protein, humanGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGSK3B protein, human

Identifiers

PMID22080951
OpenAlexW2070815451

What OpenQuestion holds

Textmetadata
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.