title: Functional analysis of the transcription repressor PLU-1/JARID1B.
abstract: The PLU-1/JARID1B nuclear protein, which is upregulated in breast cancers, belongs to the ARID family of DNA binding proteins and has strong transcriptional repression activity. To identify the target genes regulated by PLU-1/JARID1B, we overexpressed or silenced the human PLU-1/JARID1B gene in human mammary epithelial cells by using adenovirus and RNA interference systems, respectively, and then applied microarray analysis to identify candidate genes. A total of 100 genes showed inversely correlated differential expression in the two systems. Most of the candidate genes were downregulated by the overexpression of PLU-1/JARID1B, including the MT genes, the tumor suppressor gene BRCA1, and genes involved in the regulation of the M phase of the mitotic cell cycle. Chromatin immunoprecipitation assays confirmed that the metallothionein 1H (MT1H), -1F, and -1X genes are direct transcriptional targets of PLU-1/JARID1B in vivo. Furthermore, the level of trimethyl H3K4 of the MT1H promoter was increased following silencing of PLU-1/JARID1B. Both the PLU-1/JARID1B protein and the ARID domain selectively bound CG-rich DNA. The GCACA/C motif, which is abundant in metallothionein promoters, was identified as a consensus binding sequence of the PLU-1/JARID1B ARID domain. As expected from the microarray data, cells overexpressing PLU-1/JARID1B have an impaired G(2)/M checkpoint. Our study provides insight into the molecular function of the breast cancer-associated transcriptional repressor PLU-1/JARID1B.
authors: Breast Cancer Biology Group, King's College London School of Medicine, 3rd Floor, Thomas Guy House, Guy's Hospital, London SE1 9RT, United Kingdom.
authors: Angelo G
authors: AG
authors: Scibetta
authors: Samantha
authors: S
authors: Santangelo
authors: Julia
authors: J
authors: Coleman
authors: Debbie
authors: D
authors: Hall
authors: Tracy
authors: T
authors: Chaplin
authors: John
authors: J
authors: Copier
authors: Steve
authors: S
authors: Catchpole
authors: Joy
authors: J
authors: Burchell
authors: Joyce
authors: J
authors: Taylor-Papadimitriou
mesh_terms: D000818:Animals; D019313:BRCA1 Protein / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases; D042361:Mammary Glands, Human / Q000033:anatomy & histology; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D008668:Metallothionein; D056484:Jumonji Domain-Containing Histone Demethylases; C119611:KDM5B protein, human
references: Toxicol Appl Pharmacol. 1991 Sep 1;110(2):347-54
references: 1891778
references: EMBO J. 1991 Nov;10(11):3311-9
references: 1833185
references: Toxicol Appl Pharmacol. 1991 Oct;111(1):152-62
references: 1719662
references: J Cell Sci. 1992 Jul;102 ( Pt 3):437-46
references: 1506426
references: Toxicology. 1993 Jan 29;77(1-2):65-79
references: 8442019
references: Lancet. 1994 Mar 19;343(8899):692-5
references: 7907678
references: EMBO J. 1994 Jun 15;13(12):2870-5
references: 8026472
references: Cancer Res. 1994 Oct 15;54(20):5255-7
references: 7923149
references: Science. 1994 Oct 7;266(5182):120-2
references: 7939630
references: Science. 1994 Oct 7;266(5182):66-71
references: 7545954
references: Am J Hum Genet. 1995 Jan;56(1):265-71
references: 7825587
references: Proc Natl Acad Sci U S A. 1995 Jan 17;92(2):579-83
references: 7831333
references: Genes Dev. 1995 Dec 15;9(24):3067-82
references: 8543152
references: J Virol. 2005 Feb;79(4):2404-12
references: 15681441
references: Genomics. 2005 Aug;86(2):242-51
references: 15922553
references: EMBO J. 2005 Jul 6;24(13):2379-90
references: 15944735
references: Intervirology. 2005;48(6):350-61
references: 16024939
references: Mol Cell. 2005 Aug 5;19(3):381-91
references: 16061184
references: Mol Cancer Res. 2005 Oct;3(10):531-9
references: 16254187
references: Nat Rev Mol Cell Biol. 2005 Nov;6(11):838-49
references: 16261189
references: Virology. 2005 Dec 20;343(2):236-45
references: 16169035
references: Cell Cycle. 2005 Nov;4(11):1641-66
references: 16258266
references: Nature. 2006 Feb 16;439(7078):811-6
references: 16362057
references: Cell. 2006 May 5;125(3):483-95
references: 16603237
references: Cell. 2006 May 5;125(3):467-81
references: 16603238
references: Nature. 2006 Jul 20;442(7100):312-6
references: 16732292
references: Mutat Res. 2003 Dec 10;533(1-2):211-26
references: 14643422
references: Cancer Cell. 2003 Dec;4(6):483-97
references: 14706340
references: Mol Cell Biol. 2004 May;24(9):3660-9
references: 15082762
references: Proc Natl Acad Sci U S A. 1990 Apr;87(8):3137-41
references: 2326272
references: Toxicology. 1996 Feb 22;107(2):121-30
references: 8599171
references: Oncology. 1996 Mar-Apr;53(2):112-7
references: 8604236
references: Mol Cell Biol. 1996 Mar;16(3):792-9
references: 8622680
references: Nucleic Acids Res. 1996 May 1;24(9):1695-701
references: 8649988
references: Cell Motil Cytoskeleton. 1996;33(3):208-22
references: 8674140
references: Nature. 2006 Jul 20;442(7100):307-11
references: 16732293
references: Genes Dev. 2007 Mar 1;21(5):537-51
references: 17311883
references: Cell. 2007 Mar 23;128(6):1077-88
references: 17320160
references: Mol Cell. 2007 Mar 23;25(6):801-12
references: 17363312
references: Int J Cancer. 2007 Jul 15;121(2):265-75
references: 17373667
references: Nature. 2007 May 31;447(7144):601-5
references: 17468742
references: Toxicol Appl Pharmacol. 1995 Feb;130(2):229-36
references: 7871536
references: Methods Mol Biol. 2000;132:365-86
references: 10547847
references: Toxicology. 1999 Dec 20;142(1):1-13
references: 10647914
references: Cell Mol Biol (Noisy-le-grand). 2000 Mar;46(2):393-405
references: 10774928
references: Free Radic Biol Med. 2000 Jun 1;28(11):1628-37
references: 10938459
references: Int J Biochem Cell Biol. 2000 Aug;32(8):895-903
references: 10940647
references: Nature. 2000 Aug 10;406(6796):593-9
references: 10949293
references: Mol Microbiol. 2000 Oct;38(1):154-66
references: 11029697
references: J Biol Chem. 2001 Jul 27;276(30):28402-12
references: 11358960
references: Breast Cancer Res Treat. 2001 Apr;66(3):265-72
references: 11510698
references: Mol Biol Cell. 2001 Nov;12(11):3527-37
references: 11694586
references: Cell. 2001 Nov 2;107(3):323-37
references: 11701123
references: Carcinogenesis. 2002 Jan;23(1):81-6
references: 11756227
references: Cell Biol Int. 2002;26(1):19-28
references: 11779217
references: Cell Growth Differ. 2002 Mar;13(3):95-106
references: 11959810
references: Int J Cancer. 2002 Oct 20;101(6):581-8
references: 12237901
references: Mol Cell. 2003 Mar;11(3):709-19
references: 12667453
references: J Biol Chem. 2003 Jun 6;278(23):20507-13
references: 12657635
references: J Biol Chem. 2003 Sep 26;278(39):37865-73
references: 12865421
references: J Virol. 2003 Oct;77(20):11006-15
references: 14512549
references: Mech Dev. 2002 Dec;119 Suppl 1:S239-46
references: 14516692
references: Am J Pathol. 2003 Nov;163(5):2009-19
references: 14578200
references: Chromosoma. 2003 Oct;112(3):124-32
references: 14579128
references: Toxicol Appl Pharmacol. 1996 Jul;139(1):115-21
references: 8685893
references: Neurochem Int. 1996 Aug;29(2):159-66
references: 8837045
references: Cell. 1997 May 16;89(4):511-21
references: 9160743
references: Am J Pathol. 1998 Jan;152(1):23-7
references: 9422519
references: J Cell Biol. 1998 Jul 13;142(1):1-11
references: 9660858
references: Genomics. 1999 Jan 1;55(1):113-7
references: 9889005
references: Anticancer Res. 1998 Nov-Dec;18(6B):4667-72
references: 9891538
references: Anal Biochem. 1999 May 15;270(1):41-9
references: 10328763
references: Biochem Biophys Res Commun. 1999 May 10;258(2):326-31
references: 10329386
references: J Biol Chem. 1999 May 28;274(22):15633-45
references: 10336460
references: J Cell Physiol. 1999 Jul;180(1):105-13
references: 10362023
references: Mol Cell Biol. 2005 Jan;25(2):740-50
references: 15632074
references: Am J Hum Genet. 2005 Feb;76(2):227-36
references: 15586325
references: Nucleic Acids Res. 2005;33(1):66-80
references: 15640446
references: Reprod Biol Endocrinol. 2003 Oct 7;1:72
references: 14613551
references: Histopathology. 2004 Aug;45(2):103-18
references: 15279628
references: Nat Rev Cancer. 2004 Sep;4(9):665-76
references: 15343273
references: J Toxicol Environ Health. 1984;14(5-6):803-12
references: 6520888
references: J Cell Sci. 1985 Apr;75:17-33
references: 2413060
references: Annu Rev Biochem. 1986;55:913-51
references: 3527054
references: Nature. 1987 May 7-13;327(6117):31-5
references: 3553962
references: Eur J Cancer Clin Oncol. 1986 Dec;22(12):1441-52
references: 2439341
references: Science. 1988 Sep 30;241(4874):1813-5
references: 3175622
references: Biochemistry. 1988 Nov 15;27(23):8509-15
references: 3064814
references: Cell. 1989 May 5;57(3):393-401
references: 2541912
references: Cell. 1989 Sep 8;58(5):833-46
references: 2570636
references: J Biol Chem. 1990 Sep 5;265(25):15267-74
references: 2203773
references: Science. 1990 Dec 21;250(4988):1684-9
references: 2270482
references: Proc Natl Acad Sci U S A. 1991 May 1;88(9):3520-4
references: 1708884