Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer
Top Cited Papers
- 31 December 2006
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Genetics
- Vol. 39 (2), 232-236
- https://doi.org/10.1038/ng1950
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 genome1. 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 complex2,3. In cancer cells4, 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 repression2.Keywords
This publication has 30 references indexed in Scilit:
- Suz12 binds to silenced regions of the genome in a cell-type-specific mannerGenome Research, 2006
- Polycomb complexes repress developmental regulators in murine embryonic stem cellsNature, 2006
- Genome-wide mapping of Polycomb target genes unravels their roles in cell fate transitionsGenes & Development, 2006
- Control of Developmental Regulators by Polycomb in Human Embryonic Stem CellsCell, 2006
- G9a-mediated irreversible epigenetic inactivation of Oct-3/4 during early embryogenesisNature, 2006
- SUZ12 Is Required for Both the Histone Methyltransferase Activity and the Silencing Function of the EED-EZH2 ComplexMolecular Cell, 2004
- The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3Current Opinion in Genetics & Development, 2004
- Integrated genomic and epigenomic analyses pinpoint biallelic gene inactivation in tumorsNature Genetics, 2002
- A Unique Developmental Pattern of Oct-3/4DNA Methylation Is Controlled by a cis-demodification ElementPublished by Elsevier BV ,2002
- Methyltransferase Recruitment and DNA Hypermethylation of Target Promoters by an Oncogenic Transcription FactorScience, 2002