Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines
AIM： To identify the relationship between DNA hyper- methylation and histone modification at a hyperme- thylated, 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 chro...
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| Veröffentlicht in: | World journal of gastroenterology : WJG 2007-12, Vol.13 (46), p.6166-6171 |
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| creator | Meng, Chun-Feng Zhu, Xin-Jiang Peng, Guo Dai, Dong-Qiu |
| description | AIM： To identify the relationship between DNA hyper- methylation and histone modification at a hyperme- thylated, 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 rnutL homolog 1 （MLH1） genes in 2 gastric cancer cell lines, SGC-7901 and MGC-803. We used methylation- specific 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 thep16 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 alter TSA treatment, andincreased 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. |
| doi_str_mv | 10.3748/wjg.13.6166 |
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| fullrecord | <record><control><sourceid>wanfang_jour_cross</sourceid><recordid>TN_cdi_wanfang_journals_wjg200746006</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><cqvip_id>26110738</cqvip_id><wanfj_id>wjg200746006</wanfj_id><sourcerecordid>wjg200746006</sourcerecordid><originalsourceid>FETCH-LOGICAL-c380t-9b3ecd71ecd6668c81f325dcbfc3a3f5a03e96b3d38a9b8572f88451159364a23</originalsourceid><addsrcrecordid>eNpFkcFq3DAQhkVpSDZpTr0XUXoL3koaW5aPJaRJIBAI6VnIsmRra8tbSWaTF8nzVptdyEWjEd_8gm8Q-krJGupS_Nxt-jWFNaecf0IrxmhTMFGSz2hFCamLBlh9hs5j3BDCACp2is6oILypq2qF3p5MYV62wcToZo9niyeThtdRpdwWzneLNh1OyzQHHJftO5ivvfEGRzcar53vsYtY5XftVMr0zqUBpyEDKff7zMHFNOeJae6cdfo9HDuPexVTcBpr5bUJWJtxxKPzJn5BJ1aN0Vwe6wX68_vm-fqueHi8vb_-9VBoECQVTQtGdzXNB-dcaEEtsKrTrdWgwFaKgGl4Cx0I1bSiqpkVoqworRrgpWJwgX4ccnfKW-V7uZmX4POPMltlWV_JCeEZuzpgOswxBmPlNrhJhVdJidwvYY9LCnK_hEx_O9DbpZ1M98EerWfg-zFumH3_LxuUrdJ_bfYpGaeU1CDgP61RkXU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines</title><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Meng, Chun-Feng ; Zhu, Xin-Jiang ; Peng, Guo ; Dai, Dong-Qiu</creator><creatorcontrib>Meng, Chun-Feng ; Zhu, Xin-Jiang ; Peng, Guo ; Dai, Dong-Qiu</creatorcontrib><description>AIM： To identify the relationship between DNA hyper- methylation and histone modification at a hyperme- thylated, 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 rnutL homolog 1 （MLH1） genes in 2 gastric cancer cell lines, SGC-7901 and MGC-803. We used methylation- specific 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 thep16 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 alter TSA treatment, andincreased 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.</description><identifier>ISSN: 1007-9327</identifier><identifier>EISSN: 2219-2840</identifier><identifier>DOI: 10.3748/wjg.13.6166</identifier><identifier>PMID: 18069755</identifier><language>eng</language><publisher>United States: Department of Surgical Oncology, The First Affiliated Hospital,China Medical University, Shenyang 110001, Liaoning Province,China</publisher><subject>Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Azacitidine - pharmacology ; Cell Line, Tumor ; Chromatin - metabolism ; CpG Islands - genetics ; DNA ; DNA Methylation - drug effects ; DNA, Neoplasm - genetics ; DNA, Neoplasm - metabolism ; Drug Synergism ; Enzyme Inhibitors - pharmacology ; Gene Silencing - physiology ; Genes, Tumor Suppressor - physiology ; Histones - metabolism ; Humans ; Hydroxamic Acids - pharmacology ; MutL Protein Homolog 1 ; Nuclear Proteins - genetics ; Nuclear Proteins - metabolism ; p16 ; Promoter Regions, Genetic ; Stomach Neoplasms - genetics ; Stomach Neoplasms - metabolism ; Stomach Neoplasms - pathology ; Tumor Suppressor Protein p14ARF - genetics ; Tumor Suppressor Protein p14ARF - metabolism ; 单端孢霉烯 ; 组蛋白</subject><ispartof>World journal of gastroenterology : WJG, 2007-12, Vol.13 (46), p.6166-6171</ispartof><rights>Copyright © Wanfang Data Co. Ltd. All Rights Reserved.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c380t-9b3ecd71ecd6668c81f325dcbfc3a3f5a03e96b3d38a9b8572f88451159364a23</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://image.cqvip.com/vip1000/qk/84123X/84123X.jpg</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18069755$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meng, Chun-Feng</creatorcontrib><creatorcontrib>Zhu, Xin-Jiang</creatorcontrib><creatorcontrib>Peng, Guo</creatorcontrib><creatorcontrib>Dai, Dong-Qiu</creatorcontrib><title>Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines</title><title>World journal of gastroenterology : WJG</title><addtitle>World Journal of Gastroenterology</addtitle><description>AIM： To identify the relationship between DNA hyper- methylation and histone modification at a hyperme- thylated, 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 rnutL homolog 1 （MLH1） genes in 2 gastric cancer cell lines, SGC-7901 and MGC-803. We used methylation- specific 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 thep16 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 alter TSA treatment, andincreased 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.</description><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Azacitidine - pharmacology</subject><subject>Cell Line, Tumor</subject><subject>Chromatin - metabolism</subject><subject>CpG Islands - genetics</subject><subject>DNA</subject><subject>DNA Methylation - drug effects</subject><subject>DNA, Neoplasm - genetics</subject><subject>DNA, Neoplasm - metabolism</subject><subject>Drug Synergism</subject><subject>Enzyme Inhibitors - pharmacology</subject><subject>Gene Silencing - physiology</subject><subject>Genes, Tumor Suppressor - physiology</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Hydroxamic Acids - pharmacology</subject><subject>MutL Protein Homolog 1</subject><subject>Nuclear Proteins - genetics</subject><subject>Nuclear Proteins - metabolism</subject><subject>p16</subject><subject>Promoter Regions, Genetic</subject><subject>Stomach Neoplasms - genetics</subject><subject>Stomach Neoplasms - metabolism</subject><subject>Stomach Neoplasms - pathology</subject><subject>Tumor Suppressor Protein p14ARF - genetics</subject><subject>Tumor Suppressor Protein p14ARF - metabolism</subject><subject>单端孢霉烯</subject><subject>组蛋白</subject><issn>1007-9327</issn><issn>2219-2840</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkcFq3DAQhkVpSDZpTr0XUXoL3koaW5aPJaRJIBAI6VnIsmRra8tbSWaTF8nzVptdyEWjEd_8gm8Q-krJGupS_Nxt-jWFNaecf0IrxmhTMFGSz2hFCamLBlh9hs5j3BDCACp2is6oILypq2qF3p5MYV62wcToZo9niyeThtdRpdwWzneLNh1OyzQHHJftO5ivvfEGRzcar53vsYtY5XftVMr0zqUBpyEDKff7zMHFNOeJae6cdfo9HDuPexVTcBpr5bUJWJtxxKPzJn5BJ1aN0Vwe6wX68_vm-fqueHi8vb_-9VBoECQVTQtGdzXNB-dcaEEtsKrTrdWgwFaKgGl4Cx0I1bSiqpkVoqworRrgpWJwgX4ccnfKW-V7uZmX4POPMltlWV_JCeEZuzpgOswxBmPlNrhJhVdJidwvYY9LCnK_hEx_O9DbpZ1M98EerWfg-zFumH3_LxuUrdJ_bfYpGaeU1CDgP61RkXU</recordid><startdate>20071214</startdate><enddate>20071214</enddate><creator>Meng, Chun-Feng</creator><creator>Zhu, Xin-Jiang</creator><creator>Peng, Guo</creator><creator>Dai, Dong-Qiu</creator><general>Department of Surgical Oncology, The First Affiliated Hospital,China Medical University, Shenyang 110001, Liaoning Province,China</general><scope>2RA</scope><scope>92L</scope><scope>CQIGP</scope><scope>W91</scope><scope>~WA</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>2B.</scope><scope>4A8</scope><scope>92I</scope><scope>93N</scope><scope>PSX</scope><scope>TCJ</scope></search><sort><creationdate>20071214</creationdate><title>Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines</title><author>Meng, Chun-Feng ; Zhu, Xin-Jiang ; Peng, Guo ; Dai, Dong-Qiu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c380t-9b3ecd71ecd6668c81f325dcbfc3a3f5a03e96b3d38a9b8572f88451159364a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Azacitidine - pharmacology</topic><topic>Cell Line, Tumor</topic><topic>Chromatin - metabolism</topic><topic>CpG Islands - genetics</topic><topic>DNA</topic><topic>DNA Methylation - drug effects</topic><topic>DNA, Neoplasm - genetics</topic><topic>DNA, Neoplasm - metabolism</topic><topic>Drug Synergism</topic><topic>Enzyme Inhibitors - pharmacology</topic><topic>Gene Silencing - physiology</topic><topic>Genes, Tumor Suppressor - physiology</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Hydroxamic Acids - pharmacology</topic><topic>MutL Protein Homolog 1</topic><topic>Nuclear Proteins - genetics</topic><topic>Nuclear Proteins - metabolism</topic><topic>p16</topic><topic>Promoter Regions, Genetic</topic><topic>Stomach Neoplasms - genetics</topic><topic>Stomach Neoplasms - metabolism</topic><topic>Stomach Neoplasms - pathology</topic><topic>Tumor Suppressor Protein p14ARF - genetics</topic><topic>Tumor Suppressor Protein p14ARF - metabolism</topic><topic>单端孢霉烯</topic><topic>组蛋白</topic><toplevel>online_resources</toplevel><creatorcontrib>Meng, Chun-Feng</creatorcontrib><creatorcontrib>Zhu, Xin-Jiang</creatorcontrib><creatorcontrib>Peng, Guo</creatorcontrib><creatorcontrib>Dai, Dong-Qiu</creatorcontrib><collection>中文科技期刊数据库</collection><collection>中文科技期刊数据库-CALIS站点</collection><collection>中文科技期刊数据库-7.0平台</collection><collection>中文科技期刊数据库-医药卫生</collection><collection>中文科技期刊数据库- 镜像站点</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Wanfang Data Journals - Hong Kong</collection><collection>WANFANG Data Centre</collection><collection>Wanfang Data Journals</collection><collection>万方数据期刊 - 香港版</collection><collection>China Online Journals (COJ)</collection><collection>China Online Journals (COJ)</collection><jtitle>World journal of gastroenterology : WJG</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meng, Chun-Feng</au><au>Zhu, Xin-Jiang</au><au>Peng, Guo</au><au>Dai, Dong-Qiu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines</atitle><jtitle>World journal of gastroenterology : WJG</jtitle><addtitle>World Journal of Gastroenterology</addtitle><date>2007-12-14</date><risdate>2007</risdate><volume>13</volume><issue>46</issue><spage>6166</spage><epage>6171</epage><pages>6166-6171</pages><issn>1007-9327</issn><eissn>2219-2840</eissn><abstract>AIM： To identify the relationship between DNA hyper- methylation and histone modification at a hyperme- thylated, 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 rnutL homolog 1 （MLH1） genes in 2 gastric cancer cell lines, SGC-7901 and MGC-803. We used methylation- specific 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 thep16 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 alter TSA treatment, andincreased 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.</abstract><cop>United States</cop><pub>Department of Surgical Oncology, The First Affiliated Hospital,China Medical University, Shenyang 110001, Liaoning Province,China</pub><pmid>18069755</pmid><doi>10.3748/wjg.13.6166</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Azacitidine - pharmacology Cell Line, Tumor Chromatin - metabolism CpG Islands - genetics DNA DNA Methylation - drug effects DNA, Neoplasm - genetics DNA, Neoplasm - metabolism Drug Synergism Enzyme Inhibitors - pharmacology Gene Silencing - physiology Genes, Tumor Suppressor - physiology Histones - metabolism Humans Hydroxamic Acids - pharmacology MutL Protein Homolog 1 Nuclear Proteins - genetics Nuclear Proteins - metabolism p16 Promoter Regions, Genetic Stomach Neoplasms - genetics Stomach Neoplasms - metabolism Stomach Neoplasms - pathology Tumor Suppressor Protein p14ARF - genetics Tumor Suppressor Protein p14ARF - metabolism 单端孢霉烯 组蛋白 |
| title | Re-expression of methylation-induced tumor suppressor gene silencing is associated with the state of histone modification in gastric cancer cell lines |
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