title: Identification of estrogen receptor-related receptor gamma as a direct transcriptional target of angiogenin.
abstract: Nuclear translocation of angiogenin (ANG) is essential for the proliferation of its target cells. ANG promotes rRNA synthesis, while whether it regulates mRNA transcription remains unknown. Using the chromatin immunoprecipitation method, we have identified 12 ANG-binding sequences. One of these sequences lies in the estrogen receptor-related receptor gamma (ERRγ) gene which we designated as ANG-Binding Sequence within ERRγ (ABSE). ABSE exhibited ANG-dependent repressor activity in the luciferase reporter system. Down-regulation of ANG increased ERRγ expression, and active gene marker level at the ABSE region. The expression levels of ERRγ targets genes, p21(WAF/CIP) and p27(KIP1), and the occupation of ERRγ on their promoter regions were increased in ANG-deficient cells accordingly. Furthermore, knockdown of ERRγ promoted the proliferation rate in ANG-deficient breast cancer cells. Finally, immunohistochemistry staining showed negative correlation between ANG and ERRγ in breast cancer tissue. Altogether, our study provides evidence that nuclear ANG directly binds to the ABSE of ERRγ gene and inhibits ERRγ transcription to promote breast cancer cell proliferation.
authors: Institute of Environmental Medicine, Zhejiang University School of Medicine, Hangzhou, China ; Department of Gastroenterology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors: Jian
authors: J
authors: Ang
authors: Jinghao
authors: J
authors: Sheng
authors: Kairan
authors: K
authors: Lai
authors: Saisai
authors: S
authors: Wei
authors: Xiangwei
authors: X
authors: Gao
mesh_terms: D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011485:Protein Binding / Q000235:genetics; D011499:Protein Processing, Post-Translational; D012319:RNA Polymerase II / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D012259:Ribonuclease, Pancreatic / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C490917:ESRRG protein, human; D006657:Histones; D011960:Receptors, Estrogen; D012319:RNA Polymerase II; C046366:angiogenin; D012259:Ribonuclease, Pancreatic
references: Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14519-24
references: 16971483
references: Proc Natl Acad Sci U S A. 1994 Mar 1;91(5):1677-81
references: 8127865
references: Cancer Res. 2011 Apr 1;71(7):2518-28
references: 21339306
references: Biochemistry. 2003 Jan 14;42(1):121-8
references: 12515546
references: Mol Cell Biol. 2002 Jan;22(2):657-68
references: 11756560
references: Methods Enzymol. 2001;341:263-73
references: 11582782
references: Biochemistry. 1985 Sep 24;24(20):5480-6
references: 4074709
references: PLoS One. 2011 Apr 14;6(4):e18837
references: 21533145
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: Biochem Biophys Res Commun. 2001 Jul 27;285(4):909-14
references: 11467837
references: Mol Cell Biol. 2001 Oct;21(20):6820-32
references: 11564866
references: Nat Rev Mol Cell Biol. 2005 Nov;6(11):838-49
references: 16261189
references: Cancer Res. 2002 Nov 15;62(22):6510-8
references: 12438245
references: Science. 2001 Aug 10;293(5532):1074-80
references: 11498575
references: PLoS One. 2011;6(12):e28797
references: 22194915
references: Cancer Res. 2007 May 15;67(10):4904-14
references: 17510420
references: Bioinformatics. 2002 Feb;18(2):333-4
references: 11847087
references: Biochem Biophys Res Commun. 2002 Jun 7;294(2):287-92
references: 12051708
references: J Cell Biochem. 2000 Jan;76(3):452-62
references: 10649442
references: Genes Dev. 2003 Jul 15;17(14):1691-702
references: 12865296
references: Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9791-5
references: 9707554
references: Cancer Res. 2005 Feb 15;65(4):1352-60
references: 15735021
references: Nat Protoc. 2006;1(2):729-48
references: 17406303