title: Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer.
abstract: Many genes associated with CpG islands undergo de novo methylation in cancer. Studies have suggested that the pattern of this modification may be partially determined by an instructive mechanism that recognizes specifically marked regions of the genome. Using chromatin immunoprecipitation analysis, here we show that genes methylated in cancer cells are specifically packaged with nucleosomes containing histone H3 trimethylated on Lys27. This chromatin mark is established on these unmethylated CpG island genes early in development and then maintained in differentiated cell types by the presence of an EZH2-containing Polycomb complex. In cancer cells, as opposed to normal cells, the presence of this complex brings about the recruitment of DNA methyl transferases, leading to de novo methylation. These results suggest that tumor-specific targeting of de novo methylation is pre-programmed by an established epigenetic system that normally has a role in marking embryonic genes for repression.
authors.affiliation: Department of Cellular Biochemistry and Human Genetics, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
authors.forename: Yeshayahu
authors.initials: Y
authors.lastname: Schlesinger
authors.forename: Ravid
authors.initials: R
authors.lastname: Straussman
authors.forename: Ilana
authors.initials: I
authors.lastname: Keshet
authors.forename: Shlomit
authors.initials: S
authors.lastname: Farkash
authors.forename: Merav
authors.initials: M
authors.lastname: Hecht
authors.forename: Joseph
authors.initials: J
authors.lastname: Zimmerman
authors.forename: Eran
authors.initials: E
authors.lastname: Eden
authors.forename: Zohar
authors.initials: Z
authors.lastname: Yakhini
authors.forename: Etti
authors.initials: E
authors.lastname: Ben-Shushan
authors.forename: Benjamin E
authors.initials: BE
authors.lastname: Reubinoff
authors.forename: Yehudit
authors.initials: Y
authors.lastname: Bergman
authors.forename: Itamar
authors.initials: I
authors.lastname: Simon
authors.forename: Howard
authors.initials: H
authors.lastname: Cedar
mesh_terms: D018938:Caco-2 Cells; D002352:Carrier Proteins; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism; D009369:Neoplasms / Q000235:genetics*; D014759:Viral Envelope Proteins
chemical_list: D002352:Carrier Proteins; D006657:Histones; D014759:Viral Envelope Proteins; C406065:envelope H3L protein, Vaccinia virus; D008780:Methyltransferases; D008239:Lysine