KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation
Localized chromatin modifications of histone tails play an important role in regulating gene transcription, and aberration of these processes leads to carcinogenesis. Methylated histone lysine residues, a key player in chromatin remodeling, are demethylated by the JmjC class of enzymes. Here we show...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2010-05, Vol.107 (21), p.9671-9676 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Hsia, Datsun A. Tepper, Clifford G. Pochampalli, Mamata R. Hsia, Elaine Y. C. Izumiya, Chie Huerta, Steve B. Wright, Michael E. Chen, Hong-Wu Kung, Hsing-Jien Izumiya, Yoshihiro Wang, James C. |
| description | Localized chromatin modifications of histone tails play an important role in regulating gene transcription, and aberration of these processes leads to carcinogenesis. Methylated histone lysine residues, a key player in chromatin remodeling, are demethylated by the JmjC class of enzymes. Here we show that JMJD5 (now renamed KDM8), a JmjC family member, demethylates H3K36me2 and is required for cell cycle progression. Chromatin immunoprecipitation assays applied to human genome tiling arrays in conjunction with RNA microarray revealed that KDM8 occupies the coding region of cyclin A1 and directly regulates transcription. Mechanistic analyses showed that KDM8 functioned as a transcriptional activator by inhibiting HDAC recruitment via demethylation of H3K36me2, an epigenetic repressive mark. Tumor array experiments revealed KDM8 is overexpressed in several types of cancer. In addition, loss-of-function studies in MCF7 cells leads to cell cycle arrest. These studies identified KDM8 as an important cell cycle regulator. |
| doi_str_mv | 10.1073/pnas.1000401107 |
| format | Article |
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C. ; Izumiya, Chie ; Huerta, Steve B. ; Wright, Michael E. ; Chen, Hong-Wu ; Kung, Hsing-Jien ; Izumiya, Yoshihiro ; Wang, James C.</creator><creatorcontrib>Hsia, Datsun A. ; Tepper, Clifford G. ; Pochampalli, Mamata R. ; Hsia, Elaine Y. C. ; Izumiya, Chie ; Huerta, Steve B. ; Wright, Michael E. ; Chen, Hong-Wu ; Kung, Hsing-Jien ; Izumiya, Yoshihiro ; Wang, James C.</creatorcontrib><description>Localized chromatin modifications of histone tails play an important role in regulating gene transcription, and aberration of these processes leads to carcinogenesis. Methylated histone lysine residues, a key player in chromatin remodeling, are demethylated by the JmjC class of enzymes. Here we show that JMJD5 (now renamed KDM8), a JmjC family member, demethylates H3K36me2 and is required for cell cycle progression. Chromatin immunoprecipitation assays applied to human genome tiling arrays in conjunction with RNA microarray revealed that KDM8 occupies the coding region of cyclin A1 and directly regulates transcription. Mechanistic analyses showed that KDM8 functioned as a transcriptional activator by inhibiting HDAC recruitment via demethylation of H3K36me2, an epigenetic repressive mark. Tumor array experiments revealed KDM8 is overexpressed in several types of cancer. In addition, loss-of-function studies in MCF7 cells leads to cell cycle arrest. These studies identified KDM8 as an important cell cycle regulator.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1000401107</identifier><identifier>PMID: 20457893</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Acetylation ; Antibodies ; Biological Sciences ; Breast cancer ; Cancer ; Cell cycle ; Cell growth ; Cell Line, Tumor ; Cell lines ; Cell Proliferation ; Cellular biology ; Cyclin A1 - genetics ; Cyclin A1 - metabolism ; Cyclins ; Enzymes ; Gene expression ; Gene Expression Regulation, Neoplastic ; Germ cells ; Histone Demethylases - genetics ; Histone Demethylases - metabolism ; Histones ; Histones - metabolism ; Humans ; Neoplasms - genetics ; Neoplasms - metabolism ; Neoplasms - pathology ; Oncology ; Open Reading Frames ; Promoter regions ; Ribonucleic acid ; RNA ; RNA Interference ; Transcription, Genetic ; Tumors</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2010-05, Vol.107 (21), p.9671-9676</ispartof><rights>Copyright National Academy of Sciences May 25, 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c465t-b48ebff1c2773c1572ca605a270a4c5068b195565720bcbb2597e2adbf69ae63</citedby><cites>FETCH-LOGICAL-c465t-b48ebff1c2773c1572ca605a270a4c5068b195565720bcbb2597e2adbf69ae63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/107/21.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/25681658$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/25681658$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,724,777,781,800,882,27905,27906,53772,53774,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20457893$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hsia, Datsun A.</creatorcontrib><creatorcontrib>Tepper, Clifford G.</creatorcontrib><creatorcontrib>Pochampalli, Mamata R.</creatorcontrib><creatorcontrib>Hsia, Elaine Y. 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These studies identified KDM8 as an important cell cycle regulator.</description><subject>Acetylation</subject><subject>Antibodies</subject><subject>Biological Sciences</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cell cycle</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Cell Proliferation</subject><subject>Cellular biology</subject><subject>Cyclin A1 - genetics</subject><subject>Cyclin A1 - metabolism</subject><subject>Cyclins</subject><subject>Enzymes</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Germ cells</subject><subject>Histone Demethylases - genetics</subject><subject>Histone Demethylases - metabolism</subject><subject>Histones</subject><subject>Histones - metabolism</subject><subject>Humans</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - metabolism</subject><subject>Neoplasms - pathology</subject><subject>Oncology</subject><subject>Open Reading Frames</subject><subject>Promoter regions</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Interference</subject><subject>Transcription, Genetic</subject><subject>Tumors</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1vEzEQxS0EoqFw5gRYnNnW315fkKoCLWorLr1bs85sstFmHWwHKf89jhIaevKz32-eR3qEvOfsgjMrLzcT5KoYU4zXhxdkxpnjjVGOvSQzxoRtWiXUGXmT86piTrfsNTkTTGnbOjkj-e7bQ_uFAr2Vd9KsUdDlkEuckM5xjWW5GyEjLUsoFELJdJjqBWnYhbHKK05DnA_TgiZcDLF6ca-2I5TKwBQw0YDjSDcpjkOPCUql3pJXPYwZ3x3Pc_L44_vj9W1z_-vm5_XVfROU0aXpVItd3_MgrJWBaysCGKZBWAYqaGbajjutTTVYF7pOaGdRwLzrjQM08px8PcRutt0a5wGnkmD0mzSsIe18hME_d6Zh6RfxjxeuZktZAz4fA1L8vcVc_Cpu01RX9lJZZYRyqkKXByikmHPC_ukDzvy-I7_vyJ86qhMf_9_rif9XSgU-HYH95CnOesG9M5ZX4sOBWNWu0ilBm5Yb3cq_78Khdg</recordid><startdate>20100525</startdate><enddate>20100525</enddate><creator>Hsia, Datsun A.</creator><creator>Tepper, Clifford G.</creator><creator>Pochampalli, Mamata R.</creator><creator>Hsia, Elaine Y. 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C.</au><au>Izumiya, Chie</au><au>Huerta, Steve B.</au><au>Wright, Michael E.</au><au>Chen, Hong-Wu</au><au>Kung, Hsing-Jien</au><au>Izumiya, Yoshihiro</au><au>Wang, James C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2010-05-25</date><risdate>2010</risdate><volume>107</volume><issue>21</issue><spage>9671</spage><epage>9676</epage><pages>9671-9676</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Localized chromatin modifications of histone tails play an important role in regulating gene transcription, and aberration of these processes leads to carcinogenesis. Methylated histone lysine residues, a key player in chromatin remodeling, are demethylated by the JmjC class of enzymes. 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| subjects | Acetylation Antibodies Biological Sciences Breast cancer Cancer Cell cycle Cell growth Cell Line, Tumor Cell lines Cell Proliferation Cellular biology Cyclin A1 - genetics Cyclin A1 - metabolism Cyclins Enzymes Gene expression Gene Expression Regulation, Neoplastic Germ cells Histone Demethylases - genetics Histone Demethylases - metabolism Histones Histones - metabolism Humans Neoplasms - genetics Neoplasms - metabolism Neoplasms - pathology Oncology Open Reading Frames Promoter regions Ribonucleic acid RNA RNA Interference Transcription, Genetic Tumors |
| title | KDM8, a H3K36me2 histone demethylase that acts in the cyclin A1 coding region to regulate cancer cell proliferation |
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