Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines | |
Alternative Title | Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines |
Meng ChunFeng; Zhu XinJiang; Peng Guo; Dai DongQiu | |
2007 | |
Source Publication | WORLD JOURNAL OF GASTROENTEROLOGY
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ISSN | 1007-9327 |
Volume | 13Issue:46Pages:6166-6171 |
Abstract | AIM: To identify the relationship between DNA hypermethylation and histone modification at a hypermethylated, silenced tumor suppressor gene promoter in human gastric cancer cell lines and to elucidate whether alteration of DNA methylation could affect histone modification. |
Other Abstract | AIM: To identify the relationship between DNA hypermethylation and histone modification at a hypermethylated, silenced tumor suppressor gene promoter in human gastric cancer cell lines and to elucidate whether alteration of DNA methylation could affect histone modification.METHODS: We used chromatin immunoprecipitation(ChIP) assay to assess the status of histone acetylation and methylation in promoter regions of the p16 and mutL homolog 1(MLH1) genes in 2 gastric cancer cell lines, SGC-7901 and MGC-803. We used methylationspecific PCR (MSP) to evaluate the effect of 5-Aza-2'-deoxycytidine (5-Aza-dC), trichostatin A (TSA) or their combination treatment on DNA methylation status.We used RT-PCR to determine whether alterations of histone modification status after 5-Aza-dC and TSA treatment are reflected in gene expression.RESULTS: For the p16 and MLH1 genes in two cell lines,silenced loci associated with DNA hypermethylation were characterized by histone H3-K9 hypoacetylation and hypermethylation and histone H3-K4 hypomethylation.Treatment with TSA resulted in moderately increased histone H3-K9 acetylation at the silenced loci with no effect on histone H3-K9 methylation and minimal effects on gene expression. In contrast, treatment with 5-Aza-dC rapidly reduced histone H3-K9 methylation at the silenced loci and resulted in reactivation of the two genes. Combined treatment with 5-Aza-dC and TSA was synergistic in reactivating gene expression at the loci showing DNA hypermethylation. Similarly, histone H3-K4 methylation was not affected after TSA treatment, and increased moderately at the silenced loci after 5-Aza-dC treatment.CONCLUSION: Hypermethylation of DNA in promoter CpG islands is related to transcriptional silencing of tumor suppressor genes. Histone H3-K9 methylation in different regions of the promoters studied correlates with DNA methylation status of each gene in gastric cancer cells. However, histone H3-K9 acetylation and H3-K4 methylation inversely correlate with DNA methylation status of each gene in gastric cancer cells. Alteration of DNA methylation affects histone modification. |
Keyword | MICROSATELLITE INSTABILITY LYSINE-9 METHYLATION DNA METHYLATION H3 LYSINE-9 HYPERMETHYLATION HETEROCHROMATIN PROMOTER EPIGENETICS DEACETYLASE PATTERNS gastric cancer DNA hypermethylation histone methylation histone acetylation p16 mutL homolog 1 5-Aza-2'-deoxycytidine trichostatin A |
Indexed By | CSCD |
Language | 英语 |
CSCD ID | CSCD:3193869 |
Citation statistics | |
Document Type | 期刊论文 |
Identifier | http://ir.imr.ac.cn/handle/321006/142235 |
Collection | 中国科学院金属研究所 |
Affiliation | 中国科学院金属研究所 |
Recommended Citation GB/T 7714 | Meng ChunFeng,Zhu XinJiang,Peng Guo,et al. Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines[J]. WORLD JOURNAL OF GASTROENTEROLOGY,2007,13(46):6166-6171. |
APA | Meng ChunFeng,Zhu XinJiang,Peng Guo,&Dai DongQiu.(2007).Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines.WORLD JOURNAL OF GASTROENTEROLOGY,13(46),6166-6171. |
MLA | Meng ChunFeng,et al."Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines".WORLD JOURNAL OF GASTROENTEROLOGY 13.46(2007):6166-6171. |
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