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Regional hypermethylation and global hypomethylation are associated with altered chromatin conformation and histone acetylation in colorectal cancer
Author(s) -
Deng Guoren,
Nguyen Anh,
Tanaka Hirofumi,
Matsuzaki Koji,
Bell Ian,
Mehta Kshama R.,
Terdiman Jonathan P.,
Waldman Frederic M.,
Kakar Sanjay,
Gum James,
Crawley Suzanne,
Sleisenger Marvin H.,
Kim Young S.
Publication year - 2006
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.21740
Subject(s) - chromatin , trichostatin a , chromatin remodeling , histone , cancer research , dna methylation , cancer epigenetics , epigenetics , acetylation , biology , microbiology and biotechnology , histone methyltransferase , genetics , histone deacetylase , dna , gene expression , gene
Regional DNA hypermethylation and global DNA hypomethylation are 2 epigenetic alterations associated with colorectal cancers. However, their correlation with microsatellite instability (MSI) and chromosomal instability (CIN) in colorectal cancer, and their relationship with chromatin conformation and histone modification are not clear. In this study, we analyzed regional and global methylation in 16 cell lines and 64 primary colorectal cancers. We found that MSI and CIN are 2 alternative events in most cell lines and tumors. Furthermore, regional hypermethylation and global hypomethylation are also alternative events in most cases. We also observed a strong correlation between MSI and regional hypermethylation and between CIN and global hypomethylation. We further analyzed chromatin conformation and histone acetylation in cell lines with CIN or MSI. CIN cancers had open chromatin conformation and enriched histone acetylation in repetitive as well as in gene‐specific regions. MSI cancers, on the other hand, had closed chromatin conformation and low levels of histone acetylation. After a MSI cell line was treated with 5‐aza‐2′‐deoxycytidine or trichostatin A, the closed chromatin conformation became open, and histone acetylation was enriched. These observations support our hypothesis that in colorectal cancer, regional hypermethylation and global hypomethylation are associated with altered chromatin conformation and histone acetylation, which might have a causal correlation with MSI and CIN, respectively. © 2006 Wiley‐Liss, Inc.