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

SET/TAF-I beta, a subunit of the inhibitor of acetyltransferases (INHAT) complex, exhibits transcriptional repression activity by inhibiting histone acetylation. We find that SET/TAF-I beta regulates mono-ubiquitination of histone H2A at lysine 119 (H2AK119ub), which is involved in polycombmediated transcriptional repression, in HCT116 cells. In this report, we demonstrate that SET /TAF-I beta acts as an E2 ubiquitin-conjugating enzyme for PRC1independent H2AK119ub. Furthermore, we identify that MIB1 is the E3 ligase partner for SET /TAF-I beta using LC-MS /MS and in vitro ubiquitination assays. Transcriptome analysis reveals that SET /TAF-I beta 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 PRC1independent epigenetic regulatory mechanism for H2AK119ub by SET/TAF-I beta and MIB1 in colon cancer.