INHAT subunit SET/TAF-Iβ regulates PRC1-independent H2AK119 mono-ubiquitination via E3 ligase MIB1 in colon cancer.

IF 3.4 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY NAR cancer Pub Date : 2023-09-22 eCollection Date: 2023-09-01 DOI:10.1093/narcan/zcad050

Junyoung Park, Ji-Young Kim, Jin Woo Park, Joo Young Kang, Hyein Oh, Ja Young Hahm, Yun-Cheol Chae, Debabrata Chakravarti, Sang Beom Seo

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Abstract

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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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。

SET/TAF-Iβ是乙酰转移酶抑制剂（INHAT）复合物的一个亚基，通过抑制组蛋白乙酰化而表现出转录抑制活性。我们发现SET/TAF-Iβ调节HCT116细胞中组蛋白H2A在赖氨酸119（H2AK119ub）的单泛素化，该泛素化参与多梳介导的转录抑制。在本报告中，我们证明了SET/TAF-Iβ作为E2泛素偶联酶用于PRC1非依赖性H2AK119ub。此外，我们使用LC-MS/MS和体外泛素化测定确定MIB1是SET/TAF-Iβ的E3连接酶伴侣。转录组分析显示，SET/TAF-Iβ和MIB1调节HCT116细胞中与DNA复制和细胞周期进展相关的基因的表达，敲低任一蛋白都会阻碍细胞周期进展，从而减少HCT116的增殖。总之，我们的研究揭示了SET/TAF-Iβ和MIB1在癌症中对H2AK119ub的一种新的PRC1依赖性表观遗传调控机制。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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