Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer.

Article Details

Citation

Schlesinger Y, Straussman R, Keshet I, Farkash S, Hecht M, Zimmerman J, Eden E, Yakhini Z, Ben-Shushan E, Reubinoff BE, Bergman Y, Simon I, Cedar H

Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer.

Nat Genet. 2007 Feb;39(2):232-6. Epub 2006 Dec 31.

PubMed ID
17200670 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
DNA (cytosine-5)-methyltransferase 1P26358Details
Histone-lysine N-methyltransferase EZH2Q15910Details
DNA (cytosine-5)-methyltransferase 3AQ9Y6K1Details
DNA (cytosine-5)-methyltransferase 3BQ9UBC3Details