title: Reciprocal occupancy of BCL6 and STAT5 on Growth Hormone target genes: contrasting transcriptional outcomes and promoter-specific roles of p300 and HDAC3.
abstract: Expression of the Growth Hormone (GH)-stimulated gene Socs2 (Suppressor of Cytokine Signaling 2) is mediated by the transcription activator STAT5 (Signal Transducer and Activator of Transcription 5) and the transcription repressor BCL6 (B-Cell Lymphoma 6). ChIP-Sequencing identified Cish (Cytokine-Inducible SH2-containing protein) and Bcl6 as having similar patterns of reciprocal occupancy by BCL6 and STAT5 in response to GH, though GH stimulates Cish and inhibits Bcl6 expression. The co-activator p300 occupied Socs2, Cish and Bcl6 promoters, and enhanced STAT5-mediated activation of Socs2 and Cish. In contrast, on Bcl6, p300 functioned as a repressor and inhibited in conjunction with STAT5 or BCL6. The co-repressor HDAC3 (Histone deacetylase 3) inhibited the Socs2, Cish and Bcl6 promoters in the presence of STAT5. Thus transcriptional outcomes on GH-regulated genes occupied by BCL6 and STAT5 are determined in a promoter-specific fashion by co-regulatory proteins which mediate the distinction between activating and repressive transcription factors.
authors.affiliation: Cellular & Molecular Biology Program, University of Michigan, Ann Arbor, MI, USA; Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Lin
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: LaPensee
authors.affiliation: Department of Biostatistics and Bioinformatics, Emory University, Atlanta, GA, USA.
authors.forename: Zhaohui S
authors.initials: ZS
authors.lastname: Qin
authors.affiliation: Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, MI, USA. Electronic address: jeschwar@umich.edu.
authors.forename: Jessica
authors.initials: J
authors.lastname: Schwartz
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D050881:E1A-Associated p300 Protein / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D013006:Growth Hormone / Q000378:metabolism* / Q000494:pharmacology; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D051560:Proto-Oncogene Proteins c-bcl-6; D020218:Response Elements / Q000502:physiology*; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D000099186:Histone Deacetylase 3
chemical_list: D004268:DNA-Binding Proteins; D050881:E1A-Associated p300 Protein; D013006:Growth Hormone; D006655:Histone Deacetylases; D051560:Proto-Oncogene Proteins c-bcl-6; D050799:STAT5 Transcription Factor; D000099186:Histone Deacetylase 3; C490010:Bcl6 protein, mouse; C494361:Ep300 protein, mouse
keywords: Adipocytes; ChIP-Seq; Cish; Co-activator; Co-repressor; Socs2
references.citation: Mol Endocrinol. 2009 Aug;23(8):1242-54
references.pmid: 19423653
references.citation: Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10762-7
references.pmid: 9380707
references.citation: Proc Natl Acad Sci U S A. 1996 Jul 9;93(14):6947-52
references.pmid: 8692924
references.citation: Nucleic Acids Res. 2012 Sep;40(16):7776-87
references.pmid: 22723377
references.citation: J Immunol. 2008 May 1;180(9):5898-906
references.pmid: 18424709
references.citation: Mol Cell Biol. 2001 Sep;21(18):6091-101
references.pmid: 11509652
references.citation: Curr Opin Genet Dev. 2002 Apr;12(2):142-8
references.pmid: 11893486
references.citation: J Immunol. 2008 Apr 1;180(7):4805-15
references.pmid: 18354204
references.citation: BMC Genomics. 2013 Jan 16;14:4
references.pmid: 23324445
references.citation: J Endocrinol. 2010 Sep;206(3):249-59
references.pmid: 20631046
references.citation: Cell Metab. 2012 Apr 4;15(4):554-62
references.pmid: 22465074
references.citation: Cell. 2002 Feb 22;108(4):475-87
references.pmid: 11909519
references.citation: Development. 2001 Jan;128(1):57-65
references.pmid: 11092811
references.citation: Trends Biochem Sci. 2002 May;27(5):235-41
references.pmid: 12076535
references.citation: Curr Opin Genet Dev. 2008 Oct;18(5):404-10
references.pmid: 18929655
references.citation: Mol Cell. 2007 Sep 7;27(5):691-700
references.pmid: 17803935
references.citation: Nucleic Acids Res. 1998 Oct 15;26(20):4645-51
references.pmid: 9753732
references.citation: Cell. 2004 Feb 20;116(4):511-26
references.pmid: 14980219
references.citation: Oncogene. 2007 Jan 11;26(2):224-33
references.pmid: 16819511
references.citation: J Clin Invest. 2010 Dec 1;120(12):4569-82
references.pmid: 21041953
references.citation: Mol Endocrinol. 2005 Aug;19(8):2175-86
references.pmid: 15860545
references.citation: Nature. 1997 Sep 25;389(6649):349-52
references.pmid: 9311776
references.citation: J Recept Signal Transduct Res. 2009 Dec;29(6):293-8
references.pmid: 19929250
references.citation: Endocrinology. 2009 Aug;150(8):3645-54
references.pmid: 19406940
references.citation: Nat Genet. 2002 Dec;32(4):606-13
references.pmid: 12402037
references.citation: Mol Endocrinol. 2007 Jan;21(1):293-311
references.pmid: 17008382
references.citation: Genes Dev. 2010 Dec 15;24(24):2760-5
references.pmid: 21106671
references.citation: Biochem Cell Biol. 2001;79(3):337-48
references.pmid: 11467747
references.citation: Science. 2007 Nov 2;318(5851):806-9
references.pmid: 17975067
references.citation: Nucleic Acids Res. 1999 Jul 1;27(13):2722-9
references.pmid: 10373589
references.citation: Science. 2011 Mar 11;331(6022):1315-9
references.pmid: 21393543
references.citation: J Endocrinol. 2008 Jan;196(1):89-100
references.pmid: 18180320
references.citation: Genes Dev. 2008 Mar 15;22(6):711-21
references.pmid: 18347089
references.citation: Oncogene. 2000 May 15;19(21):2585-97
references.pmid: 10851057
references.citation: Int Rev Immunol. 1999;18(4):381-403
references.pmid: 10626250
references.citation: Mol Endocrinol. 1998 Oct;12(10):1582-93
references.pmid: 9773981
references.citation: J Clin Endocrinol Metab. 1988 Sep;67(3):493-500
references.pmid: 3410935
references.citation: Genes Dev. 1998 Jul 1;12(13):1953-61
references.pmid: 9649500
references.citation: Mol Endocrinol. 2006 Oct;20(10):2355-68
references.pmid: 16772529
references.citation: Genes Dev. 2006 Jun 1;20(11):1405-28
references.pmid: 16751179
references.citation: Mol Cell Biol. 2012 Sep;32(18):3732-42
references.pmid: 22801370
references.citation: Mol Cell. 2002 Jan;9(1):45-57
references.pmid: 11804585
references.citation: Mol Genet Metab. 2007 Feb;90(2):126-33
references.pmid: 17129742
references.citation: Crit Rev Oncol Hematol. 2002 Jan;41(1):1-9
references.pmid: 11796228
references.citation: Mol Endocrinol. 2007 Jun;21(6):1443-57
references.pmid: 17426286
references.citation: J Mol Endocrinol. 2006 Feb;36(1):1-7
references.pmid: 16461922
references.citation: Blood. 2003 Apr 15;101(8):2914-23
references.pmid: 12515714
references.citation: Blood. 1997 May 1;89(9):3148-54
references.pmid: 9129017
references.citation: Curr Opin Immunol. 2002 Apr;14(2):216-23
references.pmid: 11869895
references.citation: Curr Opin Immunol. 2012 Apr;24(2):146-52
references.pmid: 22342169
references.citation: Clin Transl Oncol. 2010 Jun;12(6):401-9
references.pmid: 20534395
references.citation: Mol Endocrinol. 2010 Oct;24(10):2038-49
references.pmid: 20702579
references.citation: Am J Physiol Endocrinol Metab. 2004 Mar;286(3):E393-401
references.pmid: 14761873
references.citation: Mol Carcinog. 2004 Dec;41(4):221-30
references.pmid: 15468293
references.citation: Mol Cell Biol. 2008 Apr;28(7):2175-86
references.pmid: 18212045
references.citation: BMC Bioinformatics. 2010 Jul 02;11:369
references.pmid: 20598134
references.citation: Mol Cell Biol. 2012 Nov;32(22):4611-27
references.pmid: 22966202
references.citation: Oncogene. 1998 Nov 12;17(19):2473-84
references.pmid: 9824158
references.citation: Mol Cell Biol. 2013 Aug;33(15):2879-90
references.pmid: 23716595
references.citation: J Mammary Gland Biol Neoplasia. 2008 Mar;13(1):131-45
references.pmid: 18253708
references.citation: Nature. 2008 Dec 18;456(7224):997-1000
references.pmid: 19037247
references.citation: Biochem Biophys Res Commun. 2001 Jun 1;284(1):26-32
references.pmid: 11374866
references.citation: Mol Endocrinol. 2012 Oct;26(10):1646-50
references.pmid: 22745194
references.citation: Nat Immunol. 2005 Mar;6(3):303-13
references.pmid: 15711548
references.citation: J Biol Chem. 2005 Nov 11;280(45):37489-94
references.pmid: 16166093
references.citation: J Biol Chem. 2007 Jan 12;282(2):956-67
references.pmid: 17110376
references.citation: Cell. 1996 Feb 9;84(3):331-4
references.pmid: 8608586
references.citation: J Biol Chem. 2001 May 11;276(19):16348-55
references.pmid: 11340085
references.citation: Mol Cell Biol. 2008 Apr;28(7):2213-20
references.pmid: 18227153
references.citation: Nat Rev Mol Cell Biol. 2007 Dec;8(12):983-94
references.pmid: 18037899
references.citation: Cancer Res. 2010 Feb 15;70(4):1711-21
references.pmid: 20124477
references.citation: Genes Dev. 2000 Jul 15;14(14):1810-23
references.pmid: 10898795
references.citation: Genes Chromosomes Cancer. 1995 Jul;13(3):221-4
references.pmid: 7669744
references.citation: Biochem Biophys Res Commun. 2003 Jan 10;300(2):391-6
references.pmid: 12504096
references.citation: Ann N Y Acad Sci. 1968 Feb 5;148(2):419-40
references.pmid: 5239682
references.citation: Nat Struct Mol Biol. 2013 Feb;20(2):182-7
references.pmid: 23292142
references.citation: Pathol Biol (Paris). 2007 Feb;55(1):73-83
references.pmid: 16815642
references.citation: Nature. 2011 Mar 10;471(7337):189-95
references.pmid: 21390126
references.citation: Mol Endocrinol. 2009 Nov;23(11):1914-26
references.pmid: 19797429
references.citation: Am J Hum Biol. 2011 May-Jun;23(3):325-32
references.pmid: 21484912
references.citation: Cell Rep. 2013 Aug 15;4(3):578-88
references.pmid: 23911289
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 29;107(26):11930-5
references.pmid: 20547840
references.citation: Cytokine Growth Factor Rev. 2012 Dec;23(6):283-91
references.pmid: 22989617
references.citation: Nature. 2000 Jan 6;403(6765):41-5
references.pmid: 10638745
references.citation: J Biol Chem. 2004 Dec 24;279(52):54724-30
references.pmid: 15498775
references.citation: Science. 1997 Apr 25;276(5312):589-92
references.pmid: 9110977
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 24;109(30):12058-63
references.pmid: 22783022
references.citation: Vitam Horm. 2005;70:359-86
references.pmid: 15727811
references.citation: Adv Immunol. 2010;105:193-210
references.pmid: 20510734
references.citation: Nat Immunol. 2011 Oct 30;12(12):1212-20
references.pmid: 22037603
references.citation: J Biol Chem. 2003 Nov 14;278(46):45340-51
references.pmid: 12954634
references.citation: Nucleic Acids Res. 2012 May;40(10):4461-72
references.pmid: 22319210
references.citation: Oncogene. 1997 May 22;14(20):2465-74
references.pmid: 9188861
references.citation: J Biol Chem. 2010 Jun 4;285(23):17636-47
references.pmid: 20378540
references.citation: Oncogene. 1996 Jun 6;12(11):2331-42
references.pmid: 8649773
references.citation: FEBS Lett. 2005 Feb 7;579(4):909-15
references.pmid: 15680973
references.citation: Mol Cell Biol. 2012 Feb;32(4):880-96
references.pmid: 22158971
references.citation: Cytokine Growth Factor Rev. 1999 Jun;10(2):131-57
references.pmid: 10743504
references.citation: Mol Cell Biol. 2004 Nov;24(22):10058-71
references.pmid: 15509806
references.citation: Mol Endocrinol. 2011 Apr;25(4):681-93
references.pmid: 21292824
references.citation: Endocr Relat Cancer. 2012 Sep 05;19(5):F27-45
references.pmid: 22593429
references.citation: Mol Endocrinol. 2000 Jan;14(1):114-23
references.pmid: 10628751
references.citation: J Biol Chem. 2006 Feb 17;281(7):4132-41
references.pmid: 16326703
references.citation: Endocrinology. 1998 Jul;139(7):3057-63
references.pmid: 9645676
references.citation: Cell. 1998 May 29;93(5):841-50
references.pmid: 9630227
references.citation: Mol Cell Biol. 2003 Jun;23(12):4162-73
references.pmid: 12773560
references.citation: Semin Cell Dev Biol. 2008 Aug;19(4):414-22
references.pmid: 18708154
references.citation: Endocrinology. 2001 Nov;142(11):4599-606
references.pmid: 11606424
references.citation: J Biol Chem. 1999 Sep 3;274(36):25343-9
references.pmid: 10464260
references.citation: J Biol Chem. 2004 Jul 30;279(31):32737-50
references.pmid: 15102857