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

doi:10.1093/narcan/zcad050

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

Obstetrics and Gynecology

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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 language	English (US)
Article number	zcad050
Journal	NAR Cancer
Volume	5
Issue number	3
DOIs	https://doi.org/10.1093/narcan/zcad050
State	Published - Sep 1 2023

Funding

This research was supported by the National Research Foundation of Korea (NRF) grants funded by the Korean government Ministry of Science and ICT (MSIT) (No. NRF-2021R1A2C1013553 and No. RS-2023-00220089).

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/narcan/zcad050

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

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.",

author = "Junyoung Park and Kim, {Ji Young} and Park, {Jin Woo} and Kang, {Joo Young} and Hyein Oh and Hahm, {Ja Young} and Chae, {Yun Cheol} and Debabrata Chakravarti and Seo, {Sang Beom}",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s). Published by Oxford University Press on behalf of NAR Cancer.",

year = "2023",

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doi = "10.1093/narcan/zcad050",

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AU - Park, Junyoung

AU - Kim, Ji Young

AU - Park, Jin Woo

AU - Kang, Joo Young

AU - Oh, Hyein

AU - Hahm, Ja Young

AU - Chae, Yun Cheol

AU - Chakravarti, Debabrata

AU - Seo, Sang Beom

PY - 2023/9/1

Y1 - 2023/9/1

N2 - 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.

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

Abstract

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UN SDGs

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