Widespread effects of DNA methylation and intra-motif dependencies revealed by novel transcription factor binding models.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
13 Oct 2023
13 Oct 2023
Historique:
accepted:
10
08
2023
revised:
20
07
2023
received:
01
03
2022
pubmed:
31
8
2023
medline:
31
8
2023
entrez:
31
8
2023
Statut:
ppublish
Résumé
Several studies suggested that transcription factor (TF) binding to DNA may be impaired or enhanced by DNA methylation. We present MeDeMo, a toolbox for TF motif analysis that combines information about DNA methylation with models capturing intra-motif dependencies. In a large-scale study using ChIP-seq data for 335 TFs, we identify novel TFs that show a binding behaviour associated with DNA methylation. Overall, we find that the presence of CpG methylation decreases the likelihood of binding for the majority of methylation-associated TFs. For a considerable subset of TFs, we show that intra-motif dependencies are pivotal for accurately modelling the impact of DNA methylation on TF binding. We illustrate that the novel methylation-aware TF binding models allow to predict differential ChIP-seq peaks and improve the genome-wide analysis of TF binding. Our work indicates that simplistic models that neglect the effect of DNA methylation on DNA binding may lead to systematic underperformance for methylation-associated TFs.
Identifiants
pubmed: 37650641
pii: 7256990
doi: 10.1093/nar/gkad693
pmc: PMC10570048
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e95Subventions
Organisme : German Centre for Cardiovascular Research
ID : 81Z0200101
Organisme : Cardio-Pulmonary Institute
ID : 390649896
Organisme : Goethe University
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.
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