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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Article numberzcad050
JournalNAR Cancer
Volume5
Issue number3
DOIs
StatePublished - Sep 1 2023

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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