Promoter G-quadruplex sequences are targets for base oxidation and strand cleavage during hypoxia-induced transcription.

ABSTRACT: The G-quadruplex, a non-B DNA motif that forms in certain G-rich sequences, is often located near transcription start sites in growth regulatory genes. Multiple lines of evidence show that reactive oxygen species generated as second messengers during physiologic signaling target specific DNA sequences for oxidative base modifications. Because guanine repeats are uniquely sensitive to oxidative damage, and G4 sequences are known "hot spots" for genetic mutation and DNA translocation, we hypothesized that G4 sequences are targeted for oxidative base modifications in hypoxic signaling. Approximately 25% of hypoxia-regulated genes in pulmonary artery endothelial cells harbored G4 sequences within their promoters. Chromatin immunoprecipitation showed that common base oxidation product 8-oxoguan

SUBMITTER: Clark DW 

PROVIDER: S-EPMC3377816 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature