Title: Oxidative damage targets complexes containing DNA methyltransferases, SIRT1, and polycomb members to promoter CpG Islands.
Authors: O'Hagan, Heather M; Wang, Wei; Sen, Subhojit; Destefano Shields, Christina; Lee, Stella S; Zhang, Yang W; Clements, Eriko G; Cai, Yi; Van Neste, Leander; Easwaran, Hariharan; Casero, Robert A; Sears, Cynthia L; Baylin, Stephen B
Published In Cancer Cell, (2011 Nov 15)
Abstract: Cancer cells simultaneously harbor global losses and gains in DNA methylation. We demonstrate that inducing cellular oxidative stress by hydrogen peroxide treatment recruits DNA methyltransferase 1 (DNMT1) to damaged chromatin. DNMT1 becomes part of a complex(es) containing DNMT3B and members of the polycomb repressive complex 4. Hydrogen peroxide treatment causes relocalization of these proteins from non-GC-rich to GC-rich areas. Key components are similarly enriched at gene promoters in an in vivo colitis model. Although high-expression genes enriched for members of the complex have histone mark and nascent transcription changes, CpG island-containing low-expression genes gain promoter DNA methylation. Thus, oxidative damage induces formation and relocalization of a silencing complex that may explain cancer-specific aberrant DNA methylation and transcriptional silencing.
PubMed ID: 22094255
MeSH Terms: No MeSH terms associated with this publication