title: C/EBPα negatively regulates SIRT7 expression via recruiting HDAC3 to the upstream-promoter of hepatocellular carcinoma cells.
abstract: Mammalian Sirtuin proteins (SIRTs) are homologs of yeast Sir2, and characterized as class III histone deacetylases of NAD(+) dependence. Unlike their lower counterparts that are directly involved in the extending of lifespan, mammalian SIRTs mainly function in metabolism and cellular homeostasis, among them, SIRT7 is the least understood. SIRT7 is localized in the nucleus and rich in nucleoli associated with RNA polymerase I, and correlated with cell proliferation. In contrast, SIRT7 has recently been demonstrated to specifically deacetylate H3K18ac in the chromatin, and in most cases represses proliferation. Although MicroRNA as miR-125b has been reported to down-regulate SIRT7 by binding to its 3'UTR, however, how SIRT7 gene is regulated remains unclear. Here, we identified the transcription initiation site of human SIRT7 gene at the upstream 23rd A nucleotide respective to the translational codon, and the SIRT7 is a TATA-less and initiator-less gene. The sequences in the upstream region between -256 and -129 bp are identical with important functions in the three species detected. A C/EBPα responding element is found that binds both C/EBPα and C/EBPβ in vitro. We showed TSA induced SIRT7 gene transcription and only the HDAC3, but not its catalytic domain depleted mutant, interacted with C/EBPα to occupy the C/EBPα element and repressed SIRT7 gene in the hepatocellular carcinoma cells. To our knowledge, this is the first report on the regulation mechanism of SIRT7 gene, in which, HDAC3 collaborated with C/EBPα to occupy its responding element in the upstream region of SIRT7 gene and repressed its expression in human cells.
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Gui-fen
authors.initials: GF
authors.lastname: Liu
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Jian-yi
authors.initials: JY
authors.lastname: Lu
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yan-jun
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Lang-xi
authors.initials: LX
authors.lastname: Zhang
authors.affiliation: School of Public Health, Guangxi Medical University, Nanning, China; The Key Laboratory of High-Incidence Diseases Prevention and Control, Guangxi Medical University, Nanning, China.
authors.forename: Guo-dong
authors.initials: GD
authors.lastname: Lu
authors.affiliation: School of Public Health, Guangxi Medical University, Nanning, China.
authors.forename: Ze-jun
authors.initials: ZJ
authors.lastname: Xie
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Mo-bin
authors.initials: MB
authors.lastname: Cheng
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
authors.forename: Yu-fei
authors.initials: YF
authors.lastname: Shen
authors.affiliation: National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: yezhang@ibms.pumc.edu.cn.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002843:Chromatin / Q000235:genetics; D006655:Histone Deacetylases / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D011401:Promoter Regions, Genetic; D037761:Sirtuins / Q000096:biosynthesis / Q000235:genetics*; D000099186:Histone Deacetylase 3
chemical_list: D020413:3' Untranslated Regions; D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; D002843:Chromatin; D006655:Histone Deacetylases; D037761:Sirtuins; D000099186:Histone Deacetylase 3; C515848:CEBPA protein, human; C510661:SIRT7 protein, human
keywords: C/EBP; HDAC3; SIRT7; Transcription