TY - JOUR
T1 - Effects of the stimuli-dependent enrichment of 8-oxoguanine DNA glycosylase1 on chromatinized DNA
AU - Hao, Wenjing
AU - Qi, Tianyang
AU - Pan, Lang
AU - Wang, Ruoxi
AU - Zhu, Bing
AU - Aguilera-Aguirre, Leopoldo
AU - Radak, Zsolt
AU - Hazra, Tapas K.
AU - Vlahopoulos, Spiros A.
AU - Bacsi, Attila
AU - Brasier, Allan R.
AU - Ba, Xueqing
AU - Boldogh, Istvan
N1 - Funding Information:
This work was supported by grants from the National Institute of Environmental Health and Sciences RO1 ES018948 (IB); P30 ES006676 (IB), and T32 ES007254-22 (L.A-A), National Institute of Allergic and Infectious Diseases NIAID/AI062885 (IB, ARB). National Science Foundation of China (Grant No: 31571339 to XB and 81402338 to QT), National Scholarship Fund of China, Scholarship Council (Grant No. 201506175184 and 201606620041).
Funding Information:
This work was supported by grants from the National Institute of Environmental Health and Sciences RO1 ES018948 (IB); P30 ES006676 (IB), and T32 ES007254-22 (L.A-A), National Institute of Allergic and Infectious Diseases NIAID/AI062885 (IB, ARB). National Science Foundation of China (Grant No: 31571339 to XB and 81402338 to QT), National Scholarship Fund of China, Scholarship Council (Grant No. 201506175184 and 201606620041 ).
Publisher Copyright:
© 2018
PY - 2018/9
Y1 - 2018/9
N2 - 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.
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.
KW - 8-oxoguanine
KW - Epigenetic
KW - Gene expression
KW - Oxidative DNA damage
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U2 - 10.1016/j.redox.2018.06.002
DO - 10.1016/j.redox.2018.06.002
M3 - Article
C2 - 29940424
AN - SCOPUS:85048764575
SN - 2213-2317
VL - 18
SP - 43
EP - 53
JO - Redox Biology
JF - Redox Biology
ER -