Effects of the stimuli-dependent enrichment of 8-oxoguanine DNA glycosylase1 on chromatinized DNA
| Autor: | Spiros Vlahopoulos, Zsolt Radak, Attila Bacsi, Bing Zhu, Leopoldo Aguilera-Aguirre, Allan R. Brasier, Xueqing Ba, Ruoxi Wang, Wenjing Hao, Tapas K. Hazra, Lang Pan, Istvan Boldogh, Tianyang Qi |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
GOrilla
Gene Ontology enRIchment anaLysis and visuaLizAtion tool 0301 basic medicine OGG1 8-oxoguanine DNA glycosylase-1 protein Clinical Biochemistry 8-oxoG 8-oxo-7 8-dihydroguanine Biochemistry DNA Glycosylases chemistry.chemical_compound 0302 clinical medicine Gene expression Gene Regulatory Networks CXCL-1 CXC-motif chemokine ligand-1 (protein) GEO Gene Expression Omnibus BER base excision repair lcsh:QH301-705.5 lcsh:R5-920 CCL CC chemokine ligand Epigenetic Sp1 specificity protein 1 Chromatin 3. Good health Cell biology Regulatory sequence 030220 oncology & carcinogenesis lcsh:Medicine (General) CCL gene or mRNA encoding CC chemokine ligand Research Paper CXCL human gene or mRNA encoding CXCL-1 IIR innate immune response ChIP chromatin immunoprecipitation assays TNFα tumor necrosis factor alpha TFIID transcription initiation factor II-D Biology NF-κB Nuclear Factor kappa B 03 medical and health sciences ROS reactive oxygen species AP apurinic/apyrimidinic site in DNA Humans Epigenetics Gene GO gene ontology OGG1-BER OGG1-initiated DNA base excision repair APE1 apurinic/apyrimidinic endonuclease 1 Tumor Necrosis Factor-alpha Organic Chemistry ChIP-seq chromatin immunoprecipitation assays followed by DNA sequencing RNA Pol II RNA polymerase II DNA 8-Oxoguanine Oxidative Stress HEK293 Cells 030104 developmental biology chemistry lcsh:Biology (General) Oxidative DNA damage DNA glycosylase TSS transcription start site 8-oxoguanine Reactive Oxygen Species Chromatin immunoprecipitation DNA Damage |
| Zdroj: | Redox Biology, Vol 18, Iss, Pp 43-53 (2018) Redox Biology |
| ISSN: | 2213-2317 |
| Popis: | 8-Oxoguanine DNA glycosylase 1 (OGG1) initiates the base excision repair pathway by removing one of the most abundant DNA lesions, 8-oxo-7,8-dihydroguanine (8-oxoG). Recent data showed that 8-oxoG not only is a pro-mutagenic genomic base lesion, but also functions as an epigenetic mark and that consequently OGG1 acquire distinct roles in modulation of gene expression. In support, lack of functional OGG1 in Ogg1-/- mice led to an altered expression of genes including those responsible for the aberrant innate and adaptive immune responses and susceptibility to metabolic disorders. Therefore, the present study examined stimulus-driven OGG1-DNA interactions at whole genome level using chromatin immunoprecipitation (ChIP)-coupled sequencing, and the roles of OGG1 enriched on the genome were validated by molecular and system-level approaches. Results showed that signaling levels of cellular ROS generated by TNFα, induced enrichment of OGG1 at specific sites of chromatinized DNA, primarily in the regulatory regions of genes. OGG1-ChIP-ed genes are associated with important cellular and biological processes and OGG1 enrichment was limited to a time scale required for immediate cellular responses. Prevention of OGG1-DNA interactions by siRNA depletion led to modulation of NF-κB's DNA occupancy and differential expression of genes. Taken together these data show TNFα-ROS-driven enrichment of OGG1 at gene regulatory regions in the chromatinized DNA, which is a prerequisite to modulation of gene expression for prompt cellular responses to oxidant stress. Graphical abstract The repair protein 8-oxoguanine DNA glycosylase 1 (OGG1) modulates gene expression upon its stimulus-driven binding to gene regulatory regions. ROS generated by receptor ligand interactions, metabolic processes, or environmental exposures produces 8-oxoguanine (8-oxoG) primarily in guanine-rich gene regulatory regions and inactivates OGG1's enzymatic activity by oxidizing it at cysteine residue(s) (OGG1-SOH). OGG1-SOH flips 8-oxoG out of the DNA double helix and induces alterations in adjacent DNA sequences, by which it facilitates binding of transcription factors. This leads to expression of genes and downstream cellular biological responses. Upon the cellular redox is reestablished, genomic 8-oxoG is repaired via the BER pathway. OGG1-SH, enzymatically active OGG1; OGG1-SOH, enzyatically inactive OGG1; BER, base excision repair; red star: 8-oxoguanine; red bar: gene regulatory region; blue bars: exons.fx1 |
| Databáze: | OpenAIRE |
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