Integrated requirement of non-specific and sequence-specific DNA binding in Myc-driven transcription.
DNA binding
E-box
Myc
promoter
transcription
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
17 05 2021
17 05 2021
Historique:
revised:
15
02
2021
received:
01
05
2020
accepted:
24
02
2021
pubmed:
2
4
2021
medline:
16
11
2021
entrez:
1
4
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33792944
doi: 10.15252/embj.2020105464
pmc: PMC8126922
doi:
Substances chimiques
Proto-Oncogene Proteins c-myc
0
Transcription Factors
0
DNA
9007-49-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e105464Informations de copyright
© 2021 The Authors.
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