Tip60 and p300 function antagonistically in the epigenetic regulation of HPV18 E6/E7 genes in cervical cancer HeLa cells
Background High-risk HPV is a causative factor of cervical cancer. HPV DNA fragments integrate into host genome resulting in the constitutive expression of HPV genes E6 and E7 under the regulation of transcription factors, such as p300 and Tip60. Interestingly, Tip60, a factor with HAT (histone acet...
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| Veröffentlicht in: | Genes & genomics 2020, 42(6), , pp.691-698 |
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| creator | Lai, Yongwei He, Zhao Zhang, Aowei Yan, Zhinan Zhang, Xiao Hu, Shiyue Wang, Nan He, Hongpeng |
| description | Background
High-risk HPV is a causative factor of cervical cancer. HPV DNA fragments integrate into host genome resulting in the constitutive expression of HPV genes E6 and E7 under the regulation of transcription factors, such as p300 and Tip60. Interestingly, Tip60, a factor with HAT (histone acetyl transferase) activity, represses HPV18 E6/E7 genes while another HAT p300 activates the transcription of HPV18 E6/E7.
Objective
To explore the mechanism for the opposite roles of Tip60 and p300 in the virus gene regulation, and the influence of Tip60 and p300 in histone modifications in the regulatory sequence of HPV18 genes.
Methods
Tip60 or p300 was either knocked down or overexpressed in HeLa cells. The effects on HPV E6E7 expression were determined with RT-qPCR. The association of RNA polymerase II and the enrichment of acetylated or methylated histones in HPV promoter region were measured by ChIP assays with specific antibodies.
Results
ChIP results showed that Tip60 and p300 differently affected the modifications of histone H3K9 and the deposition of nucleosomes in HPV18 long control region (LCR). HPV18 LCR in HeLa cells is bivalent chromatin carrying both the active histone H3K9 acetylation mark and the repressive histone H3K9 trimethylation mark, the balance is maintained by Tip60 and p300.
Conclusion(s)
Based on the roles of Tip60 and p300 in HPV gene regulation, chemical compounds targeting Tip60 or p300 are potential anti-cervical cancer drugs. |
| doi_str_mv | 10.1007/s13258-020-00938-4 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_nrf_k</sourceid><recordid>TN_cdi_proquest_journals_2405323938</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2402420674</sourcerecordid><originalsourceid>FETCH-LOGICAL-c409t-b2dbd07e32fb136947dd4f46f7f51f976aa9434a9705d26cc319b0c5a1ac6a9c3</originalsourceid><addsrcrecordid>eNp9kc1u1DAUhS0EoqPSF2CBLLGBRej1T-J4WVUDU2mkIjSwtRzHDm4zTrATRN8eZ1JAYlFvrnX83WNfH4ReE_hAAMRlIoyWdQEUCgDJ6oI_QxsKkhaSSvYcbYgUVSFLQc7QRUp3kBcjvOLkJTpjlEkpWblBvw5-rADr0OKRAWA3BzP5IWRl0t0QfJq80X3_gH3A03eL7eg7G2xWcbTd3OsTPTi8-_yN1HhbXW4FXoi0dBgbfy792OiQ93hn9zqLfZ9eoRdO98lePNZz9PXj9nC9K_a3n26ur_aF4SCnoqFt04KwjLqGsEpy0bbc8coJVxKXR9Racsa1FFC2tDKGEdmAKTXRptLSsHP0fvUN0al749Wg_al2g7qP6urL4UZJXvKa8My-W9kxDj9mmyZ19Gl5rQ52mJOiHCinUIkFffsfejfMMeRJFqpcPpjVmaIrZeKQUrROjdEfdXxQBNQSo1pjVDlGdYpRLdZvHq3n5mjbvy1_QssAW4GUj0Jn47-7n7D9DRXOpQs</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2405323938</pqid></control><display><type>article</type><title>Tip60 and p300 function antagonistically in the epigenetic regulation of HPV18 E6/E7 genes in cervical cancer HeLa cells</title><source>MEDLINE</source><source>Springer Nature - Complete Springer Journals</source><creator>Lai, Yongwei ; He, Zhao ; Zhang, Aowei ; Yan, Zhinan ; Zhang, Xiao ; Hu, Shiyue ; Wang, Nan ; He, Hongpeng</creator><creatorcontrib>Lai, Yongwei ; He, Zhao ; Zhang, Aowei ; Yan, Zhinan ; Zhang, Xiao ; Hu, Shiyue ; Wang, Nan ; He, Hongpeng</creatorcontrib><description>Background
High-risk HPV is a causative factor of cervical cancer. HPV DNA fragments integrate into host genome resulting in the constitutive expression of HPV genes E6 and E7 under the regulation of transcription factors, such as p300 and Tip60. Interestingly, Tip60, a factor with HAT (histone acetyl transferase) activity, represses HPV18 E6/E7 genes while another HAT p300 activates the transcription of HPV18 E6/E7.
Objective
To explore the mechanism for the opposite roles of Tip60 and p300 in the virus gene regulation, and the influence of Tip60 and p300 in histone modifications in the regulatory sequence of HPV18 genes.
Methods
Tip60 or p300 was either knocked down or overexpressed in HeLa cells. The effects on HPV E6E7 expression were determined with RT-qPCR. The association of RNA polymerase II and the enrichment of acetylated or methylated histones in HPV promoter region were measured by ChIP assays with specific antibodies.
Results
ChIP results showed that Tip60 and p300 differently affected the modifications of histone H3K9 and the deposition of nucleosomes in HPV18 long control region (LCR). HPV18 LCR in HeLa cells is bivalent chromatin carrying both the active histone H3K9 acetylation mark and the repressive histone H3K9 trimethylation mark, the balance is maintained by Tip60 and p300.
Conclusion(s)
Based on the roles of Tip60 and p300 in HPV gene regulation, chemical compounds targeting Tip60 or p300 are potential anti-cervical cancer drugs.</description><identifier>ISSN: 1976-9571</identifier><identifier>EISSN: 2092-9293</identifier><identifier>DOI: 10.1007/s13258-020-00938-4</identifier><identifier>PMID: 32399935</identifier><language>eng</language><publisher>Singapore: Springer Singapore</publisher><subject>Acetylation ; Animal Genetics and Genomics ; Biomedical and Life Sciences ; Cervical cancer ; Cervix ; Chromatin ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - metabolism ; DNA-directed RNA polymerase ; Epigenesis, Genetic ; Event-related potentials ; Gene regulation ; Genes ; Genomes ; HeLa Cells ; Histone Code ; Histones ; Human Genetics ; Human papillomavirus ; Human papillomavirus 18 - genetics ; Humans ; Life Sciences ; Lysine Acetyltransferase 5 - genetics ; Lysine Acetyltransferase 5 - metabolism ; Microbial Genetics and Genomics ; Nucleosomes ; Oncogene Proteins, Viral - genetics ; Oncogene Proteins, Viral - metabolism ; p300-CBP Transcription Factors - genetics ; p300-CBP Transcription Factors - metabolism ; Plant Genetics and Genomics ; Regulatory sequences ; Research Article ; RNA polymerase ; Transcription factors ; 생물학</subject><ispartof>Genes & Genomics, 2020, 42(6), , pp.691-698</ispartof><rights>The Genetics Society of Korea 2020</rights><rights>The Genetics Society of Korea 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c409t-b2dbd07e32fb136947dd4f46f7f51f976aa9434a9705d26cc319b0c5a1ac6a9c3</citedby><cites>FETCH-LOGICAL-c409t-b2dbd07e32fb136947dd4f46f7f51f976aa9434a9705d26cc319b0c5a1ac6a9c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13258-020-00938-4$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13258-020-00938-4$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32399935$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.kci.go.kr/kciportal/ci/sereArticleSearch/ciSereArtiView.kci?sereArticleSearchBean.artiId=ART002595248$$DAccess content in National Research Foundation of Korea (NRF)$$Hfree_for_read</backlink></links><search><creatorcontrib>Lai, Yongwei</creatorcontrib><creatorcontrib>He, Zhao</creatorcontrib><creatorcontrib>Zhang, Aowei</creatorcontrib><creatorcontrib>Yan, Zhinan</creatorcontrib><creatorcontrib>Zhang, Xiao</creatorcontrib><creatorcontrib>Hu, Shiyue</creatorcontrib><creatorcontrib>Wang, Nan</creatorcontrib><creatorcontrib>He, Hongpeng</creatorcontrib><title>Tip60 and p300 function antagonistically in the epigenetic regulation of HPV18 E6/E7 genes in cervical cancer HeLa cells</title><title>Genes & genomics</title><addtitle>Genes Genom</addtitle><addtitle>Genes Genomics</addtitle><description>Background
High-risk HPV is a causative factor of cervical cancer. HPV DNA fragments integrate into host genome resulting in the constitutive expression of HPV genes E6 and E7 under the regulation of transcription factors, such as p300 and Tip60. Interestingly, Tip60, a factor with HAT (histone acetyl transferase) activity, represses HPV18 E6/E7 genes while another HAT p300 activates the transcription of HPV18 E6/E7.
Objective
To explore the mechanism for the opposite roles of Tip60 and p300 in the virus gene regulation, and the influence of Tip60 and p300 in histone modifications in the regulatory sequence of HPV18 genes.
Methods
Tip60 or p300 was either knocked down or overexpressed in HeLa cells. The effects on HPV E6E7 expression were determined with RT-qPCR. The association of RNA polymerase II and the enrichment of acetylated or methylated histones in HPV promoter region were measured by ChIP assays with specific antibodies.
Results
ChIP results showed that Tip60 and p300 differently affected the modifications of histone H3K9 and the deposition of nucleosomes in HPV18 long control region (LCR). HPV18 LCR in HeLa cells is bivalent chromatin carrying both the active histone H3K9 acetylation mark and the repressive histone H3K9 trimethylation mark, the balance is maintained by Tip60 and p300.
Conclusion(s)
Based on the roles of Tip60 and p300 in HPV gene regulation, chemical compounds targeting Tip60 or p300 are potential anti-cervical cancer drugs.</description><subject>Acetylation</subject><subject>Animal Genetics and Genomics</subject><subject>Biomedical and Life Sciences</subject><subject>Cervical cancer</subject><subject>Cervix</subject><subject>Chromatin</subject><subject>DNA-Binding Proteins - genetics</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>DNA-directed RNA polymerase</subject><subject>Epigenesis, Genetic</subject><subject>Event-related potentials</subject><subject>Gene regulation</subject><subject>Genes</subject><subject>Genomes</subject><subject>HeLa Cells</subject><subject>Histone Code</subject><subject>Histones</subject><subject>Human Genetics</subject><subject>Human papillomavirus</subject><subject>Human papillomavirus 18 - genetics</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Lysine Acetyltransferase 5 - genetics</subject><subject>Lysine Acetyltransferase 5 - metabolism</subject><subject>Microbial Genetics and Genomics</subject><subject>Nucleosomes</subject><subject>Oncogene Proteins, Viral - genetics</subject><subject>Oncogene Proteins, Viral - metabolism</subject><subject>p300-CBP Transcription Factors - genetics</subject><subject>p300-CBP Transcription Factors - metabolism</subject><subject>Plant Genetics and Genomics</subject><subject>Regulatory sequences</subject><subject>Research Article</subject><subject>RNA polymerase</subject><subject>Transcription factors</subject><subject>생물학</subject><issn>1976-9571</issn><issn>2092-9293</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc1u1DAUhS0EoqPSF2CBLLGBRej1T-J4WVUDU2mkIjSwtRzHDm4zTrATRN8eZ1JAYlFvrnX83WNfH4ReE_hAAMRlIoyWdQEUCgDJ6oI_QxsKkhaSSvYcbYgUVSFLQc7QRUp3kBcjvOLkJTpjlEkpWblBvw5-rADr0OKRAWA3BzP5IWRl0t0QfJq80X3_gH3A03eL7eg7G2xWcbTd3OsTPTi8-_yN1HhbXW4FXoi0dBgbfy792OiQ93hn9zqLfZ9eoRdO98lePNZz9PXj9nC9K_a3n26ur_aF4SCnoqFt04KwjLqGsEpy0bbc8coJVxKXR9Racsa1FFC2tDKGEdmAKTXRptLSsHP0fvUN0al749Wg_al2g7qP6urL4UZJXvKa8My-W9kxDj9mmyZ19Gl5rQ52mJOiHCinUIkFffsfejfMMeRJFqpcPpjVmaIrZeKQUrROjdEfdXxQBNQSo1pjVDlGdYpRLdZvHq3n5mjbvy1_QssAW4GUj0Jn47-7n7D9DRXOpQs</recordid><startdate>20200601</startdate><enddate>20200601</enddate><creator>Lai, Yongwei</creator><creator>He, Zhao</creator><creator>Zhang, Aowei</creator><creator>Yan, Zhinan</creator><creator>Zhang, Xiao</creator><creator>Hu, Shiyue</creator><creator>Wang, Nan</creator><creator>He, Hongpeng</creator><general>Springer Singapore</general><general>Springer Nature B.V</general><general>한국유전학회</general><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>7X8</scope><scope>ACYCR</scope></search><sort><creationdate>20200601</creationdate><title>Tip60 and p300 function antagonistically in the epigenetic regulation of HPV18 E6/E7 genes in cervical cancer HeLa cells</title><author>Lai, Yongwei ; He, Zhao ; Zhang, Aowei ; Yan, Zhinan ; Zhang, Xiao ; Hu, Shiyue ; Wang, Nan ; He, Hongpeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c409t-b2dbd07e32fb136947dd4f46f7f51f976aa9434a9705d26cc319b0c5a1ac6a9c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acetylation</topic><topic>Animal Genetics and Genomics</topic><topic>Biomedical and Life Sciences</topic><topic>Cervical cancer</topic><topic>Cervix</topic><topic>Chromatin</topic><topic>DNA-Binding Proteins - genetics</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>DNA-directed RNA polymerase</topic><topic>Epigenesis, Genetic</topic><topic>Event-related potentials</topic><topic>Gene regulation</topic><topic>Genes</topic><topic>Genomes</topic><topic>HeLa Cells</topic><topic>Histone Code</topic><topic>Histones</topic><topic>Human Genetics</topic><topic>Human papillomavirus</topic><topic>Human papillomavirus 18 - genetics</topic><topic>Humans</topic><topic>Life Sciences</topic><topic>Lysine Acetyltransferase 5 - genetics</topic><topic>Lysine Acetyltransferase 5 - metabolism</topic><topic>Microbial Genetics and Genomics</topic><topic>Nucleosomes</topic><topic>Oncogene Proteins, Viral - genetics</topic><topic>Oncogene Proteins, Viral - metabolism</topic><topic>p300-CBP Transcription Factors - genetics</topic><topic>p300-CBP Transcription Factors - metabolism</topic><topic>Plant Genetics and Genomics</topic><topic>Regulatory sequences</topic><topic>Research Article</topic><topic>RNA polymerase</topic><topic>Transcription factors</topic><topic>생물학</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lai, Yongwei</creatorcontrib><creatorcontrib>He, Zhao</creatorcontrib><creatorcontrib>Zhang, Aowei</creatorcontrib><creatorcontrib>Yan, Zhinan</creatorcontrib><creatorcontrib>Zhang, Xiao</creatorcontrib><creatorcontrib>Hu, Shiyue</creatorcontrib><creatorcontrib>Wang, Nan</creatorcontrib><creatorcontrib>He, Hongpeng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Korean Citation Index</collection><jtitle>Genes & genomics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lai, Yongwei</au><au>He, Zhao</au><au>Zhang, Aowei</au><au>Yan, Zhinan</au><au>Zhang, Xiao</au><au>Hu, Shiyue</au><au>Wang, Nan</au><au>He, Hongpeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Tip60 and p300 function antagonistically in the epigenetic regulation of HPV18 E6/E7 genes in cervical cancer HeLa cells</atitle><jtitle>Genes & genomics</jtitle><stitle>Genes Genom</stitle><addtitle>Genes Genomics</addtitle><date>2020-06-01</date><risdate>2020</risdate><volume>42</volume><issue>6</issue><spage>691</spage><epage>698</epage><pages>691-698</pages><issn>1976-9571</issn><eissn>2092-9293</eissn><abstract>Background
High-risk HPV is a causative factor of cervical cancer. HPV DNA fragments integrate into host genome resulting in the constitutive expression of HPV genes E6 and E7 under the regulation of transcription factors, such as p300 and Tip60. Interestingly, Tip60, a factor with HAT (histone acetyl transferase) activity, represses HPV18 E6/E7 genes while another HAT p300 activates the transcription of HPV18 E6/E7.
Objective
To explore the mechanism for the opposite roles of Tip60 and p300 in the virus gene regulation, and the influence of Tip60 and p300 in histone modifications in the regulatory sequence of HPV18 genes.
Methods
Tip60 or p300 was either knocked down or overexpressed in HeLa cells. The effects on HPV E6E7 expression were determined with RT-qPCR. The association of RNA polymerase II and the enrichment of acetylated or methylated histones in HPV promoter region were measured by ChIP assays with specific antibodies.
Results
ChIP results showed that Tip60 and p300 differently affected the modifications of histone H3K9 and the deposition of nucleosomes in HPV18 long control region (LCR). HPV18 LCR in HeLa cells is bivalent chromatin carrying both the active histone H3K9 acetylation mark and the repressive histone H3K9 trimethylation mark, the balance is maintained by Tip60 and p300.
Conclusion(s)
Based on the roles of Tip60 and p300 in HPV gene regulation, chemical compounds targeting Tip60 or p300 are potential anti-cervical cancer drugs.</abstract><cop>Singapore</cop><pub>Springer Singapore</pub><pmid>32399935</pmid><doi>10.1007/s13258-020-00938-4</doi><tpages>8</tpages></addata></record> |
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| subjects | Acetylation Animal Genetics and Genomics Biomedical and Life Sciences Cervical cancer Cervix Chromatin DNA-Binding Proteins - genetics DNA-Binding Proteins - metabolism DNA-directed RNA polymerase Epigenesis, Genetic Event-related potentials Gene regulation Genes Genomes HeLa Cells Histone Code Histones Human Genetics Human papillomavirus Human papillomavirus 18 - genetics Humans Life Sciences Lysine Acetyltransferase 5 - genetics Lysine Acetyltransferase 5 - metabolism Microbial Genetics and Genomics Nucleosomes Oncogene Proteins, Viral - genetics Oncogene Proteins, Viral - metabolism p300-CBP Transcription Factors - genetics p300-CBP Transcription Factors - metabolism Plant Genetics and Genomics Regulatory sequences Research Article RNA polymerase Transcription factors 생물학 |
| title | Tip60 and p300 function antagonistically in the epigenetic regulation of HPV18 E6/E7 genes in cervical cancer HeLa cells |
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