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 Hazra, Spiros A. Vlahopoulos, Attila Bacsi, Allan R. Brasier, Xueqing Ba, Istvan Boldogh

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)43-53
Number of pages11
JournalRedox Biology
Volume18
DOIs
StatePublished - Sep 1 2018

Fingerprint

DNA Glycosylases
DNA
Genes
Gene Expression
Chromatin Immunoprecipitation
Nucleic Acid Regulatory Sequences
Modulation
Gene expression
Chromatin
8-hydroxyguanine
Genome
Biological Phenomena
Adaptive Immunity
Regulator Genes
Innate Immunity
Oxidants
Epigenomics
DNA Repair
Small Interfering RNA
Repair

Keywords

  • 8-oxoguanine
  • Epigenetic
  • Gene expression
  • Oxidative DNA damage

ASJC Scopus subject areas

  • Organic Chemistry
  • Clinical Biochemistry

Cite this

Effects of the stimuli-dependent enrichment of 8-oxoguanine DNA glycosylase1 on chromatinized DNA. / Hao, Wenjing; Qi, Tianyang; Pan, Lang; Wang, Ruoxi; Zhu, Bing; Aguilera-Aguirre, Leopoldo; Radak, Zsolt; Hazra, Tapas; Vlahopoulos, Spiros A.; Bacsi, Attila; Brasier, Allan R.; Ba, Xueqing; Boldogh, Istvan.

In: Redox Biology, Vol. 18, 01.09.2018, p. 43-53.

Research output: Contribution to journalArticle

Hao, W, Qi, T, Pan, L, Wang, R, Zhu, B, Aguilera-Aguirre, L, Radak, Z, Hazra, T, Vlahopoulos, SA, Bacsi, A, Brasier, AR, Ba, X & Boldogh, I 2018, 'Effects of the stimuli-dependent enrichment of 8-oxoguanine DNA glycosylase1 on chromatinized DNA' Redox Biology, vol. 18, pp. 43-53. https://doi.org/10.1016/j.redox.2018.06.002
Hao, Wenjing ; Qi, Tianyang ; Pan, Lang ; Wang, Ruoxi ; Zhu, Bing ; Aguilera-Aguirre, Leopoldo ; Radak, Zsolt ; Hazra, Tapas ; Vlahopoulos, Spiros A. ; Bacsi, Attila ; Brasier, Allan R. ; Ba, Xueqing ; Boldogh, Istvan. / Effects of the stimuli-dependent enrichment of 8-oxoguanine DNA glycosylase1 on chromatinized DNA. In: Redox Biology. 2018 ; Vol. 18. pp. 43-53.
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AU - Aguilera-Aguirre, Leopoldo

AU - Radak, Zsolt

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AU - Vlahopoulos, Spiros A.

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AB - 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.

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