title: UHRF2 decreases H3K9ac expression by interacting with it through the PHD and SRA/YDG domain in HepG2 hepatocellular carcinoma cells.
abstract: Ubiquitin-like with PHD and ring finger domains 2 (UHRF2) is a multi-domain E3 ubiquitin ligase which is involved in epigenetic regulation and plays an essential role in tumorigenesis. However, the role of UHRF2 in histone H3 acetylation has not yet been fully elucidated and few studies have reported its role in hepatocellular carcinoma (HCC). In this study, we examined the correlation between UHRF2 and acetylated H3 in HCC. Immunohistochemistry and western blot analysis demonstrated that the levels of histone H3 lysine 9 acetylation (H3K9ac) and histone H3 lysine 14 acetylation (H3K14ac) were higher in the HCC tissues and HepG2 HCC cells compared with the adjacent non-tumor tissues and L02 normal cells. The level of UHRF2 was higher in the HCC tissues compared with the adjacent non-tumor tissues, but its expression did not exhibit a significant difference between the HepG2 HCC cells and the L02 normal cells. In addition, when comparing the HCC tissues, a higher expression of UHRF2 correlated with a lower expression of H3K9ac in the HCC tissues. The overexpression of UHRF2 increased the expression of H3K9ac in L02 normal cells (P<0.01), but decreased the expression of H3K9ac in HepG2 cancer cells (P<0.05). Moreover, immunofluorescence staining and co-immunoprecipitation assay indicated that UHRF2 co-localized and interacted with H3K9ac in L02 and HepG2 cells and the plant homeodomain (PHD) finger domain was the key domain for UHRF2 directly binding to H3K9ac. Taken together, these results suggest that UHRF2 decreases the expression of H3K9ac in HepG2 HCC cells and interacts with it through the PHD domain.
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Linglin
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Shengyuan
authors.initials: S
authors.lastname: Zeng
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Bai
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Junxia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.
authors.forename: Changzhu
authors.initials: C
authors.lastname: Duan
mesh_terms: D000107:Acetylation; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D056945:Hep G2 Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D011485:Protein Binding; D000072417:Protein Domains; D021381:Protein Transport; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D044767:Ubiquitin-Protein Ligases / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D006657:Histones; C465619:UHRF2 protein, human; D044767:Ubiquitin-Protein Ligases; D008239:Lysine