论文库首页  论文库
 
论文编号:
论文题目: SPOP-containing complex regulates SETD2 stability and H3K36me3-coupled alternative splicing
英文论文题目: SPOP-containing complex regulates SETD2 stability and H3K36me3-coupled alternative splicing
第一作者: Zhu, K; Lei, PJ; Ju, LG; Wang, X; Huang, K; Yang, B; Shao, CW; Zhu, Y; Wei, G; Fu, XD; Li, LY; Wu, M
英文第一作者: Zhu, K; Lei, PJ; Ju, LG; Wang, X; Huang, K; Yang, B; Shao, CW; Zhu, Y; Wei, G; Fu, XD; Li, LY; Wu, M
联系作者: Wu, M (reprint author), Wuhan Univ, Hubei Key Lab Cell Homeostasis, Hubei Key Lab Devel Originated Dis, Dept Biochem & Mol Biol,Coll Life Sci, Wuhan 430072, Hubei, Peoples R China.
英文联系作者: Wu, M (reprint author), Wuhan Univ, Hubei Key Lab Cell Homeostasis, Hubei Key Lab Devel Originated Dis, Dept Biochem & Mol Biol,Coll Life Sci, Wuhan 430072, Hubei, Peoples R China.
外单位作者单位:
英文外单位作者单位:
发表年度: 2017
卷: 45
期: 1
页码: 92-105
摘要: Trimethylation of histone H3K36 is a chromatin mark associated with active gene expression, which has been implicated in coupling transcription with mRNA splicing and DNA damage response. SETD2 is a major H3K36 trimethyltransferase, which has been implicated as a tumor suppressor in mammals. Here, we report the regulation of SETD2 protein stability by the proteasome system, and the identification of SPOP, a key subunit of the CUL3 ubiquitin E3 ligase complex, as a SETD2-interacting protein. We demonstrate that SPOP is critically involved in SETD2 stability control and that the SPOP/CUL3 complex is responsible for SETD2 polyubiquitination both in vivo and in vitro. ChIP-Seq analysis and biochemical experiments demonstrate that modulation of SPOP expression confers differential H3K36me3 on SETD2 target genes, and induce H3K36me3-coupled alternative splicing events. Together, these findings establish a functional connection between oncogenic SPOP and tumor suppressive SETD2 in the dynamic regulation of gene expression on chromatin.
英文摘要: Trimethylation of histone H3K36 is a chromatin mark associated with active gene expression, which has been implicated in coupling transcription with mRNA splicing and DNA damage response. SETD2 is a major H3K36 trimethyltransferase, which has been implicated as a tumor suppressor in mammals. Here, we report the regulation of SETD2 protein stability by the proteasome system, and the identification of SPOP, a key subunit of the CUL3 ubiquitin E3 ligase complex, as a SETD2-interacting protein. We demonstrate that SPOP is critically involved in SETD2 stability control and that the SPOP/CUL3 complex is responsible for SETD2 polyubiquitination both in vivo and in vitro. ChIP-Seq analysis and biochemical experiments demonstrate that modulation of SPOP expression confers differential H3K36me3 on SETD2 target genes, and induce H3K36me3-coupled alternative splicing events. Together, these findings establish a functional connection between oncogenic SPOP and tumor suppressive SETD2 in the dynamic regulation of gene expression on chromatin.
刊物名称: NUCLEIC ACIDS RESEARCH
英文刊物名称: NUCLEIC ACIDS RESEARCH
论文全文:
英文论文全文:
全文链接:
其它备注:
英文其它备注:
学科: Biochemistry & Molecular Biology
英文学科: Biochemistry & Molecular Biology
影响因子: 10.162
第一作者所在部门:
英文第一作者所在部门:
论文出处:
英文论文出处:
论文类别: Article
英文论文类别: Article
参与作者:
英文参与作者:
 
2014 中国科学院上海生命科学研究院 版权所有