Structural insights into i-motif DNA structures in sequences from the insulin-linked polymorphic region.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
20 Aug 2024
20 Aug 2024
Historique:
received:
12
07
2023
accepted:
12
07
2024
medline:
21
8
2024
pubmed:
21
8
2024
entrez:
20
8
2024
Statut:
epublish
Résumé
The insulin-linked polymorphic region is a variable number of tandem repeats region of DNA in the promoter of the insulin gene that regulates transcription of insulin. This region is known to form the alternative DNA structures, i-motifs and G-quadruplexes. Individuals have different sequence variants of tandem repeats and although previous work investigated the effects of some variants on G-quadruplex formation, there is not a clear picture of the relationship between the sequence diversity, the DNA structures formed, and the functional effects on insulin gene expression. Here we show that different sequence variants of the insulin linked polymorphic region form different DNA structures in vitro. Additionally, reporter genes in cellulo indicate that insulin expression may change depending on which DNA structures form. We report the crystal structure and dynamics of an intramolecular i-motif, which reveal sequences within the loop regions forming additional stabilising interactions that are critical to formation of stable i-motif structures. The outcomes of this work reveal the detail in formation of stable i-motif DNA structures, with potential for rational based drug design for compounds to target i-motif DNA.
Identifiants
pubmed: 39164244
doi: 10.1038/s41467-024-50553-0
pii: 10.1038/s41467-024-50553-0
doi:
Substances chimiques
Insulin
0
DNA
9007-49-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7119Subventions
Organisme : Diabetes UK
ID : 18/0005820
Pays : United Kingdom
Organisme : European Commission (EC)
ID : 692068: BISON
Informations de copyright
© 2024. The Author(s).
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