Evidence map›Paper›PMID 33792944›Full record

ArticleThe EMBO journal2021

Integrated requirement of non-specific and sequence-specific DNA binding in Myc-driven transcription.

Paola Pellanda, Mattia Dalsass, Marco Filipuzzi, Alessia Loffreda, Alessandro Verrecchia, Virginia Castillo Cano, Hugo Thabussot, Mirko Doni, Marco J Morelli, Laura Soucek and 6 more

Open access · greenAbstract read
In one paragraph

Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
2.6field-weighted citation impact, top 9% 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

25 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Article
  3. bioRxiv : the preprint server for biology · 2025
    Article
  4. Article
  5. Review
  6. Fueling the fire-a pan-cancer analysis of MYC-regulated lipid metabolism.Frontiers in cell and developmental biology · 2025
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. MYC: a complex problem.Trends in cell biology · 2023
    Review
  15. Article
  16. Review
  17. Article
  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

16 authors at 5 institutions in 2 countries.

Paola PellandaEuropean Institute of Oncology (IEO) - IRCCS, Milan, Italy.
Mattia DalsassEuropean Institute of Oncology (IEO) - IRCCS, Milan, Italy.ORCID 0000-0003-1712-1071
Marco FilipuzziEuropean Institute of Oncology (IEO) - IRCCS, Milan, Italy.ORCID 0000-0002-4584-4114
Alessia LoffredaExperimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID 0000-0003-4523-5666
Alessandro VerrecchiaEuropean Institute of Oncology (IEO) - IRCCS, Milan, Italy.ORCID 0000-0002-8596-6650
Virginia Castillo CanoPeptomyc S.L., Barcelona, Spain.
Hugo ThabussotPeptomyc S.L., Barcelona, Spain.
Mirko DoniEuropean Institute of Oncology (IEO) - IRCCS, Milan, Italy.ORCID 0000-0001-7099-2701
Marco J MorelliCenter for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.ORCID 0000-0003-1862-667X
Laura SoucekPeptomyc S.L., Barcelona, Spain.ORCID 0000-0002-4750-7971
Theresia KressCenter for Genomic Science of IIT@SEMM, Fondazione Istituto Italiano di Tecnologia (IIT), Milan, Italy.
Davide MazzaExperimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.ORCID 0000-0003-2776-4142
Marina MapelliEuropean Institute of Oncology (IEO) - IRCCS, Milan, Italy.ORCID 0000-0001-8502-0649
Marie-Eve BeaulieuPeptomyc S.L., Barcelona, Spain.ORCID 0000-0001-5224-8436
Bruno AmatiEuropean Institute of Oncology (IEO) - IRCCS, Milan, Italy.ORCID 0000-0002-2958-1799
Arianna SabòEuropean Institute of Oncology (IEO) - IRCCS, Milan, Italy.ORCID 0000-0002-9542-0045
European Institute of Oncology · ITFC Barcelona · ESItalian Institute of Technology · ITVita-Salute San Raffaele University · ITInstitució Catalana de Recerca i Estudis Avançats · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Eukaryotic transcription factors recognize specific DNA sequence motifs, but are also endowed with generic, non-specific DNA-binding activity. How these binding modes are integrated to determine select transcriptional outputs remains unresolved. We addressed this question by site-directed mutagenesis of the Myc transcription factor. Impairment of non-specific DNA backbone contacts caused pervasive loss of genome interactions and gene regulation, associated with increased intra-nuclear mobility of the Myc protein in murine cells. In contrast, a mutant lacking base-specific contacts retained DNA-binding and mobility profiles comparable to those of the wild-type protein, but failed to recognize its consensus binding motif (E-box) and could not activate Myc-target genes. Incidentally, this mutant gained weak affinity for an alternative motif, driving aberrant activation of different genes. Altogether, our data show that non-specific DNA binding is required to engage onto genomic regulatory regions; sequence recognition in turn contributes to transcriptional activation, acting at distinct levels: stabilization and positioning of Myc onto DNA, and-unexpectedly-promotion of its transcriptional activity. Hence, seemingly pervasive genome interaction profiles, as detected by ChIP-seq, actually encompass diverse DNA-binding modalities, driving defined, sequence-dependent transcriptional responses.

Indexed as

Base SequenceBinding SitesDNAGene Expression RegulationProtein StabilityProto-Oncogene Proteins c-mycTranscription FactorsDNAProto-Oncogene Proteins c-mycTranscription FactorsDNA bindingE-boxMycpromotertranscription

Identifiers

PMID33792944
PMCPMC8126922
OpenAlexW3142651336

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.