Junyoung Park, Ji-Young Kim, Jin Woo Park, Joo Young Kang, Hyein Oh, Ja Young Hahm, Yun-Cheol Chae, Debabrata Chakravarti, Sang Beom Seo
{"title":"INHAT亚单位SET/TAF-Iβ通过E3连接酶MIB1在癌症中调节PRC1依赖性H2AK119单泛素化。","authors":"Junyoung Park, Ji-Young Kim, Jin Woo Park, Joo Young Kang, Hyein Oh, Ja Young Hahm, Yun-Cheol Chae, Debabrata Chakravarti, Sang Beom Seo","doi":"10.1093/narcan/zcad050","DOIUrl":null,"url":null,"abstract":"<p><p>SET/TAF-Iβ, a subunit of the inhibitor of acetyltransferases (INHAT) complex, exhibits transcriptional repression activity by inhibiting histone acetylation. We find that SET/TAF-Iβ regulates mono-ubiquitination of histone H2A at lysine 119 (H2AK119ub), which is involved in polycomb-mediated transcriptional repression, in HCT116 cells. In this report, we demonstrate that SET/TAF-Iβ acts as an E2 ubiquitin-conjugating enzyme for PRC1-independent H2AK119ub. Furthermore, we identify that MIB1 is the E3 ligase partner for SET/TAF-Iβ using LC-MS/MS and <i>in vitro</i> ubiquitination assays. Transcriptome analysis reveals that SET/TAF-Iβ and MIB1 regulate the expression of genes related to DNA replication and cell cycle progression in HCT116 cells, and knockdown of either protein reduces proliferation of HCT116 cells by impeding cell cycle progression. Together, our study reveals a novel PRC1-independent epigenetic regulatory mechanism for H2AK119ub by SET/TAF-Iβ and MIB1 in colon cancer.</p>","PeriodicalId":94149,"journal":{"name":"NAR cancer","volume":null,"pages":null},"PeriodicalIF":3.4000,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516711/pdf/","citationCount":"0","resultStr":"{\"title\":\"INHAT subunit SET/TAF-Iβ regulates PRC1-independent H2AK119 mono-ubiquitination via E3 ligase MIB1 in colon cancer.\",\"authors\":\"Junyoung Park, Ji-Young Kim, Jin Woo Park, Joo Young Kang, Hyein Oh, Ja Young Hahm, Yun-Cheol Chae, Debabrata Chakravarti, Sang Beom Seo\",\"doi\":\"10.1093/narcan/zcad050\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>SET/TAF-Iβ, a subunit of the inhibitor of acetyltransferases (INHAT) complex, exhibits transcriptional repression activity by inhibiting histone acetylation. We find that SET/TAF-Iβ regulates mono-ubiquitination of histone H2A at lysine 119 (H2AK119ub), which is involved in polycomb-mediated transcriptional repression, in HCT116 cells. In this report, we demonstrate that SET/TAF-Iβ acts as an E2 ubiquitin-conjugating enzyme for PRC1-independent H2AK119ub. Furthermore, we identify that MIB1 is the E3 ligase partner for SET/TAF-Iβ using LC-MS/MS and <i>in vitro</i> ubiquitination assays. Transcriptome analysis reveals that SET/TAF-Iβ and MIB1 regulate the expression of genes related to DNA replication and cell cycle progression in HCT116 cells, and knockdown of either protein reduces proliferation of HCT116 cells by impeding cell cycle progression. Together, our study reveals a novel PRC1-independent epigenetic regulatory mechanism for H2AK119ub by SET/TAF-Iβ and MIB1 in colon cancer.</p>\",\"PeriodicalId\":94149,\"journal\":{\"name\":\"NAR cancer\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2023-09-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516711/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"NAR cancer\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1093/narcan/zcad050\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/9/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"NAR cancer","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1093/narcan/zcad050","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
INHAT subunit SET/TAF-Iβ regulates PRC1-independent H2AK119 mono-ubiquitination via E3 ligase MIB1 in colon cancer.
SET/TAF-Iβ, a subunit of the inhibitor of acetyltransferases (INHAT) complex, exhibits transcriptional repression activity by inhibiting histone acetylation. We find that SET/TAF-Iβ regulates mono-ubiquitination of histone H2A at lysine 119 (H2AK119ub), which is involved in polycomb-mediated transcriptional repression, in HCT116 cells. In this report, we demonstrate that SET/TAF-Iβ acts as an E2 ubiquitin-conjugating enzyme for PRC1-independent H2AK119ub. Furthermore, we identify that MIB1 is the E3 ligase partner for SET/TAF-Iβ using LC-MS/MS and in vitro ubiquitination assays. Transcriptome analysis reveals that SET/TAF-Iβ and MIB1 regulate the expression of genes related to DNA replication and cell cycle progression in HCT116 cells, and knockdown of either protein reduces proliferation of HCT116 cells by impeding cell cycle progression. Together, our study reveals a novel PRC1-independent epigenetic regulatory mechanism for H2AK119ub by SET/TAF-Iβ and MIB1 in colon cancer.
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