Sequencing the Mouse Genome for the Oxidatively Modified Base 8-Oxo-7,8-dihydroguanine by OG-Seq.
Oxidative damage to the genome can yield the base 8-oxo-7,8-dihydroguanine (OG). In vitro studies suggested OG would preferentially form in 5'-GG-3' sequence contexts after exposure to reactive oxygen species. Herein, OG locations in the genome were studied by development of "OG-Seq" to sequence OG sites via next-generation sequencing at ∼0.15-kb resolution. The results of this study found ∼10 000 regions of OG enrichment in WT mouse embryonic fibroblasts and ∼18 000 regions when the OG repair glycosylase Ogg1 was knocked out. Gene promoters and UTRs harbor more OG-enriched sites than expected if the sites were randomly distributed throughout the genome and correlate with reactive 5'-GG-3' sequences, a result supporting decades of in vitro studies. Sequencing of OG paves the way to address chemical and biological questions surrounding this modified DNA base, such as its role in disease-specific mutations and its epigenetic potential in gene regulation.
Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
Yun
0000-0002-6624-0934
Y
Ding
Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
Aaron M
0000-0002-2000-0310
AM
Fleming
Department of Chemistry, University of Utah , 315 South 1400 East, Salt Lake City, Utah 84112-0850, United States.
Cynthia J
0000-0001-7253-8529
CJ
Burrows
D000818:Animals; D045647:DNA Glycosylases / Q000737:chemistry*; D016678:Genome / Q000235:genetics; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D010084:Oxidation-Reduction
C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human