Promoter/enhancer-based controllability of regulatory networks.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
03 03 2022
03 03 2022
Historique:
received:
27
09
2021
accepted:
19
01
2022
entrez:
4
3
2022
pubmed:
5
3
2022
medline:
14
4
2022
Statut:
epublish
Résumé
Understanding the mechanisms of tissue-specific transcriptional regulation is crucial as mis-regulation can cause a broad range of diseases. Here, we investigated transcription factors (TF) that are indispensable for the topological control of tissue specific and cell-type specific regulatory networks as a function of their binding to regulatory elements on promoters and enhancers of corresponding target genes. In particular, we found that promoter-binding TFs that were indispensable for regulatory network control regulate genes that are tissue-specifically expressed and overexpressed in corresponding cancer types. In turn, indispensable, enhancer-binding TFs were enriched with disease and signaling genes as they control an increasing number of cell-type specific regulatory networks. Their target genes were cell-type specific for blood and immune-related cell-types and over-expressed in blood-related cancers. Notably, target genes of indispensable enhancer-binding TFs in cell-type specific regulatory networks were enriched with cancer drug targets, while target genes of indispensable promoter-binding TFs were bona-fide targets of cancer drugs in corresponding tissues. Our results emphasize the significant role control analysis of regulatory networks plays in our understanding of transcriptional regulation, demonstrating potential therapeutic implications in tissue-specific drug discovery research.
Identifiants
pubmed: 35241702
doi: 10.1038/s41598-022-07035-4
pii: 10.1038/s41598-022-07035-4
pmc: PMC8894475
doi:
Substances chimiques
Transcription Factors
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3528Informations de copyright
© 2022. The Author(s).
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