G-quadruplex DNA contributes to RNA polymerase II-mediated 3D chromatin architecture.
Nucleic Acids Res
; 51(16): 8434-8446, 2023 09 08.
Article
en En
| MEDLINE
| ID: mdl-37427784
ABSTRACT
High-order chromatin organization plays an important role in biological processes and disease development. Previous studies revealed a widespread occurrence of guanine quadruplex (G4) structures in the human genome, with enrichment in gene regulatory regions, especially in promoters. However, it remains unclear whether G4 structures contribute to RNA polymerase II (RNAPII)-mediated long-range DNA interactions and transcription activity. In this study, we conducted an intuitive overlapping analysis of previously published RNAPII ChIA-PET (chromatin interaction analysis with paired-end tag) and BG4 ChIP-seq (chromatin immunoprecipitation followed by sequencing using a G4 structure-specific antibody) data. We observed a strong positive correlation between RNAPII-linked DNA loops and G4 structures in chromatin. Additionally, our RNAPII HiChIP-seq (in situ Hi-C followed by ChIP-seq) results showed that treatment of HepG2 cells with pyridostatin (PDS), a small-molecule G4-binding ligand, could diminish RNAPII-linked long-range DNA contacts, with more pronounced diminutions being observed for those contacts involving G4 structure loci. RNA sequencing data revealed that PDS treatment modulates the expression of not only genes with G4 structures in their promoters, but also those with promoters being connected with distal G4s through RNAPII-linked long-range DNA interactions. Together, our data substantiate the function of DNA G4s in RNAPII-associated DNA looping and transcription regulation.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Cromatina
/
G-Cuádruplex
Límite:
Humans
Idioma:
En
Revista:
Nucleic Acids Res
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos