Polycomb Group Protein EZH1 Regulates NF-?B Signaling Pathway

Polycomb group (PcG) proteins are critical for embryonic development and cell differentiation. Numerous studies show that PcG proteins also regulate many other biological processes, such as cell proliferation, apoptosis, cancer and immunity. The main function of PcG proteins is to suppress gene transcription through histone modification. However, as a member of PcG proteins, EZH1 is required for active gene transcription. And the mechanism has remained unclear.NF-?B signaling pathway involves in a lot of key biological processes, such as the development of immune system, inflammation and apoptosis. The dyregulation of NF-?B signaling pathway is related with immune deseases and cancer. The mechanisms about pathway regulation in cell cytoplasm is clear. However, little is known about its regulation in nucleus. Here, we found that EZH1 interacts with UXT (a NF-?B transcriptional co-activator) through yeast two hybrid screening. The immunoprecipitation in mammalian cells confirmed the interaction between UXT and EZH1. UXT interacts with RELA and is required for the activation of NF-?B signaling pathway. Similar to UXT, the deficiency of EZH1 attenuates the activation of NF-?B target genes. EZH1 does not regulate the degradation of I?B? or the translocation of RELA into nuclear. Instead, EZH1 regulates the recruitment of RELA to target genes. Moreover, EZH1 interacts with RNA Pol ? and is required for the recruitment of RNA Pol II to NF-?B target genes. The core subunits of PRC2 are EZH1/2, EED and SUZ12. Interestingly, our results suggest that only EZH1 and SUZ12 interact with UXT. SUZ12 also regulates both the activation of NF-?B target genes and the recruitment of RELA. SUZ12 interacts with RNA Pol II and required for its recruitment to NF-?B target genes. Importantly, knockdown of EZH1 sensitizes HCT116 cells to TNF-a-induced apoptosis. Our research reveals the new function of an untypical EZH1/SUZ12 complex and further illustrates the underlying mechanism in promoting transcription. Also, our study provides evidence to show the critical regulatory steps in nucleus for NF-?B signaling. These suggest EZH1/SUZ12 complex as a potential target for clinical studies.