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EZH1/SUZ12 complex positively regulates the transcription of NF-κB target genes via interaction with UXT

ABSTRACT: EZH1 is one of polycomb group genes which positively regulates transcription in the genome-wide scale. However, the underlying mechanisms still remain elusive. Here we report that EZH1 physically interacts with UXT, one small chaperon-like transcription co-activator of NF-κB. UXT specifically interacts with EZH1 and SUZ12, but not EED or EZH2. Similar to UXT, RNA interference of EZH1 and SUZ12 in the cell impairs the transcriptional activation of NF-κB target genes after TNFα treatment, and increases the induced cell death. Then RNA-Sequencing analysis was used to analysis the transcriptome in HCT116 cells after EZH1 or UXT knockdown. EZH1 or UXT deficiency nearly impaired the induced expression of all the genes by TNFα. ChIP-Sequencing was used to analysis the H3K27me1, H3K27me2 and H3K27me3 levels in HCT116 cells after EZH1 or UXT knockdown. However, the results show that H3K27 mono-, di- and trimethylation on NF-κB target genes are not affected with EZH1 or UXT deficiency. EZH1 does not affect the translocation of RELA/p65 from cytosol to nuclear either. Instead, EZH1 regulates the recruitment of RELA/p65 and RNA POLII to target genes. Taken together, our study demonstrates EZH1 as a positive regulator for NF-κB signaling and reveals the underlying mechanism how EZH1 and UXT work together in transcription regulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE75217 | GEO | 2016/05/11

SECONDARY ACCESSION(S): PRJNA302893

REPOSITORIES: GEO

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