Clustered DNA methylation changes in polycomb target genes in early-stage liver cancer
| Autor: | Chih Jan Ko, Yao Li Chen, Ping Yi Lin, Yi Ru Chu, Ming Han Kuo, Pei-Yi Chu, Mei Yu Pai, Tim H M Huang, Wan Ling Chuang, Shu-Huei Hsiao, Chun Hsin Tung, Chun Chun Chang, Yu-Wei Leu, Chia-Chen Hsu |
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| Rok vydání: | 2012 |
| Předmět: |
Cellular differentiation
Biophysics Kruppel-Like Transcription Factors Polycomb-Group Proteins Biology medicine.disease_cause Biochemistry Minor Histocompatibility Antigens Cell Line Tumor Histone methylation medicine Humans Epigenetics Gene Silencing Molecular Biology RNA-Directed DNA Methylation Epigenomics Calcium-Binding Proteins Liver Neoplasms Cell Biology Methylation Hep G2 Cells DNA Methylation Chromatin Gene Expression Regulation Neoplastic Genetic Loci DNA methylation Cancer research Carcinogenesis Apoptosis Regulatory Proteins Microtubule-Associated Proteins |
| Zdroj: | Biochemical and biophysical research communications. 425(2) |
| ISSN: | 1090-2104 |
| Popis: | Polycomb-group proteins mark specific chromatin conformations in embryonic and somatic stem cells that are critical for maintenance of their "stemness". These proteins also mark altered chromatin modifications identified in various cancers. In normal differentiated cells or advanced cancerous cells, these polycomb-associated loci are frequently associated with increased DNA methylation. It has thus been hypothesized that changes in DNA methylation status within polycomb-associated loci may dictate cell fate and that abnormal methylation within these loci may be associated with tumor development. To assess this, we examined the methylation states of four polycomb target loci -Trip10, Casp8AP2, ENSA, and ZNF484 - in liver cancer. These four targets were selected because their methylation levels are increased during mesenchymal stem cell-to-liver differentiation. We found that these four loci were hypomethylated in most early-stage liver cancer specimens. For comparison, two non-polycomb tumor suppressor genes, HIC1 and RassF1A, were also examined. Whereas the methylation level of HIC1 did not differ significantly between normal and tumor samples, RassF1A was significantly hypermethylated in liver tumor samples. Unsupervised clustering analysis classified the methylation changes within polycomb and non-polycomb targets to be independent, indicating independent epigenetic evolution. Thus, pre-deposited polycomb marks within somatic stem cells may contribute to the determination of methylation changes during hepatic tumorigenesis. |
| Databáze: | OpenAIRE |
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