Frequent switching of polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line

Einav Nili Gal-Yam, Gerda Egger, Leo Iniguez, Heather Holster, Steingrímur Einarsson, Xinmin Zhang, Joy C. Lin, Gangning Liang, Peter A. Jones, Amos Tanay

Research output: Contribution to journalArticle

247 Citations (Scopus)

Abstract

Epigenetic reprogramming is commonly observed in cancer, and is hypothesized to involve multiple mechanisms, including DNA methylation and Polycomb repressive complexes (PRCs). Here we devise a new experimental and analytical strategy using customized high-density tiling arrays to investigate coordinated patterns of gene expression, DNA methylation, and Polycomb marks which differentiate prostate cancer cells from their normal counterparts. Three major changes in the epigenomic landscape distinguish the two cell types. Developmentally significant genes containing CpG islands which are silenced by PRCs in the normal cells acquire DNA methylation silencing and lose their PRC marks (epigenetic switching). Because these genes are normally silent this switch does not cause de novo repression but might significantly reduce epigenetic plasticity. Two other groups of genes are silenced by either de novo DNA methylation without PRC occupancy (5mC reprogramming) or by de novo PRC occupancy without DNA methylation (PRC reprogramming). Our data suggest that the two silencing mechanisms act in parallel to reprogram the cancer epigenome and that DNA hypermethylation may replace Polycomb-based repression near key regulatory genes, possibly reducing their regulatory plasticity.

Original languageEnglish (US)
Pages (from-to)12979-12984
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number35
DOIs
StatePublished - Sep 2 2008

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DNA Methylation
Prostatic Neoplasms
Epigenomics
Cell Line
DNA
Genes
CpG Islands
Regulator Genes
Neoplasms
Gene Expression

Keywords

  • DNA methylation
  • MeDIP normalization
  • Polycomb
  • Spatial clustering

ASJC Scopus subject areas

  • General

Cite this

Frequent switching of polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line. / Gal-Yam, Einav Nili; Egger, Gerda; Iniguez, Leo; Holster, Heather; Einarsson, Steingrímur; Zhang, Xinmin; Lin, Joy C.; Liang, Gangning; Jones, Peter A.; Tanay, Amos.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 35, 02.09.2008, p. 12979-12984.

Research output: Contribution to journalArticle

Gal-Yam, Einav Nili ; Egger, Gerda ; Iniguez, Leo ; Holster, Heather ; Einarsson, Steingrímur ; Zhang, Xinmin ; Lin, Joy C. ; Liang, Gangning ; Jones, Peter A. ; Tanay, Amos. / Frequent switching of polycomb repressive marks and DNA hypermethylation in the PC3 prostate cancer cell line. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 35. pp. 12979-12984.
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