8-OxoG in GC-rich Sp1 binding sites enhances gene transcription in adipose tissue of juvenile mice

The oxidation of guanine to 8-oxoguanine (8-oxoG) is the most common type of oxidative DNA lesion. There is a growing body of evidence indicating that 8-oxoG is not only pre-mutagenic, but also plays an essential role in modulating gene expression along with its cognate repair proteins. In this stud...

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Bibliographic Details
Published in:Scientific reports 2019-10, Vol.9 (1), p.15618-12, Article 15618
Main Authors: Park, Jong Woo, Han, Young In, Kim, Sung Woo, Kim, Tae Min, Yeom, Su Cheong, Kang, Jaeku, Park, Joonghoon
Format: Article
Language:English
Subjects:
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8-Hydroxyguanine
Adipose tissue
Adipose Tissue - metabolism
Animals
Base Sequence
Binding Sites
Estrogens
GC Rich Sequence
Gene expression
Gene regulation
Genomics
Guanine
Guanine - analogs & derivatives
Guanine - metabolism
HEK293 Cells
Humanities and Social Sciences
Humans
Liquid chromatography
Mass spectrometry
Mass spectroscopy
Menopause
Mice
multidisciplinary
Nucleotide Motifs
Oxidative stress
Ribonucleic acid
RNA
Science
Science (multidisciplinary)
Sp1 protein
Sp1 Transcription Factor - chemistry
Sp1 Transcription Factor - metabolism
Transcription, Genetic
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Summary:The oxidation of guanine to 8-oxoguanine (8-oxoG) is the most common type of oxidative DNA lesion. There is a growing body of evidence indicating that 8-oxoG is not only pre-mutagenic, but also plays an essential role in modulating gene expression along with its cognate repair proteins. In this study, we investigated the relationship between 8-oxoG formed under intrinsic oxidative stress conditions and gene expression in adipose and lung tissues of juvenile mice. We observed that transcriptional activity and the number of active genes were significantly correlated with the distribution of 8-oxoG in gene promoter regions, as determined by reverse-phase liquid chromatography/mass spectrometry (RP-LC/MS), and 8-oxoG and RNA sequencing. Gene regulation by 8-oxoG was not associated with the degree of 8-oxoG formation. Instead, genes with GC-rich transcription factor binding sites in their promoters became more active with increasing 8-oxoG abundance as also demonstrated by specificity protein 1 (Sp1)- and estrogen response element (ERE)-luciferase assays in human embryonic kidney (HEK293T) cells. These results indicate that the occurrence of 8-oxoG in GC-rich Sp1 binding sites is important for gene regulation during adipose tissue development.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-019-52139-z