Effects of the stimuli-dependent enrichment of 8-oxoguanine DNA glycosylase1 on chromatinized DNA

Wenjing Hao, Tianyang Qi, Lang Pan, Ruoxi Wang, Bing Zhu, Leopoldo Aguilera-Aguirre, Zsolt Radak, Tapas K. Hazra, Spiros A. Vlahopoulos, Attila Bacsi, Allan R. Brasier, Xueqing Ba, Istvan Boldogh*

*この研究の対応する著者

研究成果: Article査読

32 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)43-53
ページ数11
ジャーナルRedox Biology
18
DOI
出版ステータスPublished - 2018 9月
外部発表はい

ASJC Scopus subject areas

  • 有機化学
  • 臨床生化学

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