期刊
CANCER CELL
卷 35, 期 2, 页码 297-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2019.01.004
关键词
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资金
- prostate cancer WGBS (Cancer Institute NSW, Australia, program grant)
- National Health and Medical Research Council, Australia (NHMRC) [1088144]
- NHMRC Fellowship [1063559]
- Cancer Australia, Australia [1044458]
- NHMRC [1113904, 1081858]
- Bill and Patricia Ritchie Foundation, Australia
- UNSW Sydney University International Postgraduate Award (UIPA), Australia
- National Health and Medical Research Council of Australia [1113904, 1088144, 1081858, 1063559] Funding Source: NHMRC
Promoter CpG islands are typically unmethylated in normal cells, but in cancer a proportion are subject to hypermethylation. Using methylome sequencing we identified CpG islands that display partial methylation encroachment across the 5' or 3' CpG island borders. CpG island methylation encroachment is widespread in prostate and breast cancer and commonly associates with gene suppression. We show that the pattern of H3K4me1 at CpG island borders in normal cells predicts the different modes of cancer CpG island hypermethylation. Notably, genetic manipulation of Kmt2d results in concordant alterations in H3K4me1 levels and CpG island border DNA methylation encroachment. Our findings suggest a role for H3K4me1 in the demarcation of CpG island methylation borders in normal cells, which become eroded in cancer.
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