Evidence map›Paper›PMID 30085281›Full record

ArticleNucleic acids research2018

Shared nucleotide flanks confer transcriptional competency to bZip core motifs.

Daniel M Cohen, Hee-Woong Lim, Kyoung-Jae Won, David J Steger

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2018. 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
0.5field-weighted citation impact, top 35% 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

17 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. DNA-Protein Binding is Dominated by Short Anchoring Elements.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  6. Article
  7. Article
  8. GermlineeLife · 2024
    Article
  9. GermlinebioRxiv : the preprint server for biology · 2024
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Motif grammar: The basis of the language of gene expression.Computational and structural biotechnology journal · 2020
    Review
  17. A novel upstream transcription factor 1 target geneBiochemistry and biophysics reports · 2019
    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

4 authors at 2 institutions in 2 countries.

Daniel M CohenDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Hee-Woong LimThe Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
Kyoung-Jae WonThe Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
David J StegerDivision of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA.
University of Pennsylvania · USUniversity of Copenhagen · DK

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI DOUGLAS J EPSTEIN · 1986 to 2026
$48.3M
Transcriptional and epigenomic control of adipose tissue development and functionR01DK098542 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI STEGER, DAVID J. · 2013 to 2017
$1.7M
Tracing transcriptomic changes to uncover unknown roles of TZDsR01DK106027 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SEALE, PATRICK, WON, KYOUNG JAE · 2015 to 2019
$1.7M
NIDDK NIH HHS P30 DK019525NIDDK NIH HHS R01 DK098542NIDDK NIH HHS R01 DK106027
6 · The paper itself

Abstract

Sequence-specific DNA binding recruits transcription factors (TFs) to the genome to regulate gene expression. Here, we perform high resolution mapping of CEBP proteins to determine how sequence dictates genomic occupancy. We demonstrate a fundamental difference between the sequence repertoire utilized by CEBPs in vivo versus the palindromic sequence preference reported by classical in vitro models, by identifying a palindromic motif at <1% of the genomic binding sites. On the native genome, CEBPs bind a diversity of related 10 bp sequences resulting from the fusion of degenerate and canonical half-sites. Altered DNA specificity of CEBPs in cells occurs through heterodimerization with other bZip TFs, and approximately 40% of CEBP-binding sites in primary human cells harbor motifs characteristic of CEBP heterodimers. In addition, we uncover an important role for sequence bias at core-motif-flanking bases for CEBPs and demonstrate that flanking bases regulate motif function across mammalian bZip TFs. Favorable flanking bases confer efficient TF occupancy and transcriptional activity, and DNA shape may explain how the flanks alter TF binding. Importantly, motif optimization within the 10-mer is strongly correlated with cell-type-independent recruitment of CEBPβ, providing key insight into how sequence sub-optimization affects genomic occupancy of widely expressed CEBPs across cell types.

Indexed as

Nucleotide MotifsTranscription, GeneticAnimalsBase SequenceBasic-Leucine Zipper Transcription FactorsBinding SitesCCAAT-Enhancer-Binding ProteinsChromatin ImmunoprecipitationDimerizationHigh-Throughput Nucleotide SequencingHumansMicePolymorphism, Single NucleotideProtein BindingSpecific Pathogen-Free OrganismsStructure-Activity RelationshipBasic-Leucine Zipper Transcription FactorsCCAAT-Enhancer-Binding Proteins

Identifiers

PMID30085281
PMCPMC6144830
OpenAlexW2951926359

What Socratic holds

Textmetadata
LicenceCC BY-NC
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 Socratic graph.