Evidence map›Paper›PMID 28719624›Full record

ArticlePloS one2017

Sequence-specific DNA binding by MYC/MAX to low-affinity non-E-box motifs.

Michael Allevato, Eugene Bolotin, Mark Grossman, Daniel Mane-Padros, Frances M Sladek, Ernest Martinez

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

30 citing papers in PubMed, 61 citations in OpenAlex.

  1. Article
  2. Article
  3. MYC as a key target for melanoma therapy.Frontiers in cell and developmental biology · 2026
    Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Plants (Basel, Switzerland) · 2024
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. 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

6 authors at 1 institution in 1 country.

Michael AllevatoDepartment of Biochemistry, University of California Riverside, Riverside, California, United States of America.
Eugene BolotinDepartment of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America.
Mark GrossmanDepartment of Biochemistry, University of California Riverside, Riverside, California, United States of America.
Daniel Mane-PadrosDepartment of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America.
Frances M SladekDepartment of Cell Biology and Neuroscience, University of California Riverside, Riverside, California, United States of America.
Ernest MartinezDepartment of Biochemistry, University of California Riverside, Riverside, California, United States of America.ORCID http://orcid.org/0000-0002-6326-4121
University of California, Riverside · US

Funding

UC Riverside MARC U* Star Undergraduate Research ProgramT34GM062756 · NIGMS · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI MARTINEZ, ERNEST · 2001 to 2022
$8.7M
Functional characterization of the long non-coding RNA Scirocco in development anR01CA158540 · NCI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI MARTINEZ, ERNEST · 2012 to 2017
$1.5M
Nuclear Receptor DNA Binding in Human Physiology and DiseaseR01DK094707 · NIDDK · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI SLADEK, FRANCES M. · 2012 to 2015
$1.5M
Mechanisms of Transcription Regulation by c-MycR01CA100464 · NCI · UNIVERSITY OF CALIFORNIA RIVERSIDE · PI MARTINEZ, ERNEST · 2004 to 2008
$1.2M
NCI NIH HHS R01 CA100464NCI NIH HHS R01 CA158540NIDDK NIH HHS R01 DK094707NIGMS NIH HHS T34 GM062756
6 · The paper itself

Abstract

The MYC oncoprotein regulates transcription of a large fraction of the genome as an obligatory heterodimer with the transcription factor MAX. The MYC:MAX heterodimer and MAX:MAX homodimer (hereafter MYC/MAX) bind Enhancer box (E-box) DNA elements (CANNTG) and have the greatest affinity for the canonical MYC E-box (CME) CACGTG. However, MYC:MAX also recognizes E-box variants and was reported to bind DNA in a "non-specific" fashion in vitro and in vivo. Here, in order to identify potential additional non-canonical binding sites for MYC/MAX, we employed high throughput in vitro protein-binding microarrays, along with electrophoretic mobility-shift assays and bioinformatic analyses of MYC-bound genomic loci in vivo. We identified all hexameric motifs preferentially bound by MYC/MAX in vitro, which include the low-affinity non-E-box sequence AACGTT, and found that the vast majority (87%) of MYC-bound genomic sites in a human B cell line contain at least one of the top 21 motifs bound by MYC:MAX in vitro. We further show that high MYC/MAX concentrations are needed for specific binding to the low-affinity sequence AACGTT in vitro and that elevated MYC levels in vivo more markedly increase the occupancy of AACGTT sites relative to CME sites, especially at distal intergenic and intragenic loci. Hence, MYC binds diverse DNA motifs with a broad range of affinities in a sequence-specific and dose-dependent manner, suggesting that MYC overexpression has more selective effects on the tumor transcriptome than previously thought.

Indexed as

Nucleotide MotifsBase SequenceBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsDNAGene Expression RegulationGenomicsHumansProtein BindingProtein MultimerizationProto-Oncogene Proteins c-mycSubstrate SpecificityBasic Helix-Loop-Helix Leucine Zipper Transcription FactorsDNAMAX protein, humanProto-Oncogene Proteins c-myc

Identifiers

PMID28719624
PMCPMC5515408
OpenAlexW2737747761

What OpenQuestion holds

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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.