DNA Hypermethylation Encroachment at CpG Island Borders in Cancer Is Predisposed by H3K4 Monomethylation Patterns
| Autor: | Lisa A. Miosge, Grady C. Smith, Jenny Z. Song, Amanda Khoury, Shalima S. Nair, Sue Mei Lim, Ozren Bogdanovic, Clare Stirzaker, Qian Du, Ruth Pidsley, Tim J Peters, Christopher C. Goodnow, Etienne Masle-Farquhar, Ksenia Skvortsova, James G. Kench, Elena Zotenko, Wenjia Qu, Susan J. Clark, Phuc-Loi Luu, Mark A. Rubin, Cathryn M. Gould, Joanne H. Reed, Lisa G. Horvath, Jose M. Polo, Yolanda Colino-Sanguino |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cpg island methylation Male Cancer Research CpG island hypermethylation Dna hypermethylation Biology Methylation Histones 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Neoplasms medicine Animals Humans Promoter Regions Genetic 610 Medicine & health Gene Mice Knockout Cancer Cell Biology DNA Neoplasm Histone-Lysine N-Methyltransferase DNA Methylation medicine.disease Neoplasm Proteins DNA-Binding Proteins Gene Expression Regulation Neoplastic Mice Inbred C57BL 030104 developmental biology Oncology CpG site 030220 oncology & carcinogenesis DNA methylation Cancer research 5-Methylcytosine CpG Islands Female Myeloid-Lymphoid Leukemia Protein |
| DOI: | 10.7892/boris.136284 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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