28 February 2022
Centro Congressi Partenope
Europe/Rome timezone

8-oxodG accumulation within super-enhancers marks fragile CTCF-mediated chromatin loops.

28 Feb 2022, 12:40
10m
Aula Magna (Centro Congressi Partenope)

Aula Magna

Centro Congressi Partenope

Via Partenope, 36 - Napoli

Speaker

Prof. Amente Stefano (Department of Molecular Medicine and Medical Biotechnologies, University of Naples ‘Federico II’, Naples, Italy)

Description

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 role in many genome-related functions. However, the number of studies addressing the 8-oxodG epigenetic role at a genomic level is still low and the mechanisms controlling genomic 8-oxodG accumulation/maintenance have not yet been fully characterized.
In this study, we report the identification and the 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 provides novel mechanistic insights on the intrinsic fragility of chromatin loops containing oxidized enhancers-promoters pairs and suggests that 8-oxodG accumulation in these latter occurs in a transcription-dependent manner.

Department Department of Molecular Medicine and Medical Biotechnologies, University of Naples ‘Federico II’, Naples, Italy

Primary authors

Dr. Scala Giovanni (1Department of Biology, University of Naples ‘Federico II’, Naples, Italy) Dr. Gorini Francesca (Department of Molecular Medicine and Medical Biotechnologies, University of Naples ‘Federico II’, Naples, Italy) Dr. Ambrosio Susanna (1Department of Biology, University of Naples ‘Federico II’, Naples, Italy) Dr. Chiariello Andrea Maria (Department of Physics, University of Naples Federico II, and INFN, Naples, Italy) Prof. Nicodemi Mario Prof. Lania Luigi (Department of Molecular Medicine and Medical Biotechnologies, University of Naples ‘Federico II’, Naples, Italy) Prof. Majello Barbara (Department of Biology, University of Naples ‘Federico II’, Naples, Italy) Prof. Amente Stefano (Department of Molecular Medicine and Medical Biotechnologies, University of Naples ‘Federico II’, Naples, Italy)

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