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8-oxodG accumulation within super-enhancers marks fragile CTCF-mediated chromatin loops.
Scala, Giovanni; Gorini, Francesca; Ambrosio, Susanna; Chiariello, Andrea M; Nicodemi, Mario; Lania, Luigi; Majello, Barbara; Amente, Stefano.
Afiliação
  • Scala G; Department of Biology, University of Naples 'Federico II', Naples, Italy.
  • Gorini F; Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Naples, Italy.
  • Ambrosio S; Department of Biology, University of Naples 'Federico II', Naples, Italy.
  • Chiariello AM; Department of Physics, University of Naples Federico II, and INFN, Naples, Italy.
  • Nicodemi M; Department of Physics, University of Naples Federico II, and INFN, Naples, Italy.
  • Lania L; Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Naples, Italy.
  • Majello B; Department of Biology, University of Naples 'Federico II', Naples, Italy.
  • Amente S; Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', Naples, Italy.
Nucleic Acids Res ; 50(6): 3292-3306, 2022 04 08.
Article em En | MEDLINE | ID: mdl-35234932
ABSTRACT
8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a major product of the DNA oxidization process, has been proposed to have an epigenetic function in gene regulation and has been associated with genome instability. NGS-based methodologies are contributing to the characterization of the 8-oxodG function in the genome. However, the 8-oxodG epigenetic role at a genomic level and the mechanisms controlling the genomic 8-oxodG accumulation/maintenance have not yet been fully characterized. In this study, we report the identification and characterization of a set of enhancer regions accumulating 8-oxodG in human epithelial cells. We found that these oxidized enhancers are mainly super-enhancers and are associated with bidirectional-transcribed enhancer RNAs and DNA Damage Response activation. Moreover, using ChIA-PET and HiC data, we identified specific CTCF-mediated chromatin loops in which the oxidized enhancer and promoter regions physically associate. Oxidized enhancers and their associated chromatin loops accumulate endogenous double-strand breaks which are in turn repaired by NHEJ pathway through a transcription-dependent mechanism. Our work suggests that 8-oxodG accumulation in enhancers-promoters pairs occurs in a transcription-dependent manner and provides novel mechanistic insights on the intrinsic fragility of chromatin loops containing oxidized enhancers-promoters interactions.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Elementos Facilitadores Genéticos / Epigênese Genética / Fator de Ligação a CCCTC / 8-Hidroxi-2'-Desoxiguanosina Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Elementos Facilitadores Genéticos / Epigênese Genética / Fator de Ligação a CCCTC / 8-Hidroxi-2'-Desoxiguanosina Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Nucleic Acids Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Itália