title: The EZH1-SUZ12 complex positively regulates the transcription of NF-κB target genes through interaction with UXT.
abstract: Unlike other members of the polycomb group protein family, EZH1 has been shown to positively associate with active transcription on a genome-wide scale. However, the underlying mechanism for this behavior still remains elusive. Here, we report that EZH1 physically interacts with UXT, a small chaperon-like transcription co-activator. UXT specifically interacts with EZH1 and SUZ12, but not EED. Similar to upon knockdown of UXT, knockdown of EZH1 or SUZ12 through RNA interference in the cell impairs the transcriptional activation of nuclear factor (NF)-κB target genes induced by TNFα. EZH1 deficiency also increases TNFα-induced cell death. Interestingly, chromatin immunoprecipitation and the following next-generation sequencing analysis show that H3K27 mono-, di- and tri-methylation on NF-κB target genes are not affected in EZH1- or UXT-deficient cells. EZH1 also does not affect the translocation of the p65 subunit of NF-κB (also known as RELA) from the cytosol to the nucleus. Instead, EZH1 and SUZ12 regulate the recruitment of p65 and RNA Pol II to target genes. Taken together, our study shows that EZH1 and SUZ12 act as positive regulators for NF-κB signaling and demonstrates that EZH1, SUZ12 and UXT work synergistically to regulate pathway activation in the nucleus.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Shuai-Kun
authors.initials: SK
authors.lastname: Su
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Chun-Yuan
authors.initials: CY
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Pin-Ji
authors.initials: PJ
authors.lastname: Lei
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Quan-Yi
authors.initials: QY
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Cai
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, Hubei 430072, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, Hubei 430072, China wumin@whu.edu.cn lilianyun@whu.edu.cn.
authors.forename: Lianyun
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Life Sciences, Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan University, Wuhan, Hubei 430072, China wumin@whu.edu.cn lilianyun@whu.edu.cn.
authors.forename: Min
authors.identifier: 0000-0003-1372-4764
authors.initials: M
authors.lastname: Wu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D045325:HCT116 Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008745:Methylation / Q000187:drug effects; D018832:Molecular Chaperones; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D012319:RNA Polymerase II / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; D006657:Histones; D018832:Molecular Chaperones; D016328:NF-kappa B; D009363:Neoplasm Proteins; C430461:SUZ12 protein, human; D051996:Transcription Factor RelA; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C118920:UXT protein, human; C103523:EZH1 protein, human; D063151:Polycomb Repressive Complex 2; D012319:RNA Polymerase II; D008239:Lysine
keywords: EZH1; Histone methylation; NF-κB signaling pathway; Transcription regulation; UXT