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An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences
Molecular Cell
  • Charles A. Ishak, London Regional Cancer Program
  • Aren E. Marshall, London Regional Cancer Program
  • Daniel T. Passos, London Regional Cancer Program
  • Carlee R. White, Children's Health Research Institute, London, ON
  • Seung J. Kim, London Regional Cancer Program
  • Matthew J. Cecchini, London Regional Cancer Program
  • Sara Ferwati, London Regional Cancer Program
  • William A. MacDonald, Magee-Womens Research Institute
  • Christopher J. Howlett, Western University
  • Ian D. Welch, The University of British Columbia
  • Seth M. Rubin, University of California, Santa Cruz
  • Mellissa R.W. Mann, Magee-Womens Research Institute
  • Frederick A. Dick, London Regional Cancer Program
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Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include simple repeats, satellites, LINEs, and endogenous retroviruses as well as transposon fragments. We generated a mutant mouse strain carrying an F832A mutation in Rb1 that is defective for recruitment to repetitive sequences. Loss of pRB-EZH2 complexes from repeats disperses H3K27me3 from these genomic locations and permits repeat expression. Consistent with maintenance of H3K27me3 at the Hox clusters, these mice are developmentally normal. However, susceptibility to lymphoma suggests that pRB-EZH2 recruitment to repetitive elements may be cancer relevant.

Citation Information
Charles A. Ishak, Aren E. Marshall, Daniel T. Passos, Carlee R. White, et al.. "An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences" Molecular Cell Vol. 64 Iss. 6 (2016) p. 1074 - 1087
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