title: Catalysis-dependent stabilization of Bre1 fine-tunes histone H2B ubiquitylation to regulate gene transcription.
abstract: Monoubiquitylation of histone H2B on Lys123 (H2BK123ub1) plays a multifaceted role in diverse DNA-templated processes, yet the mechanistic details by which this modification is regulated are not fully elucidated. Here we show in yeast that H2BK123ub1 is regulated in part through the protein stability of the E3 ubiquitin ligase Bre1. We found that Bre1 stability is controlled by the Rtf1 subunit of the polymerase-associated factor (PAF) complex and through the ability of Bre1 to catalyze H2BK123ub1. Using a domain in Rtf1 that stabilizes Bre1, we show that inappropriate Bre1 levels lead to defects in gene regulation. Collectively, these data uncover a novel quality control mechanism used by the cell to maintain proper Bre1 and H2BK123ub1 levels, thereby ensuring proper control of gene expression.
authors.affiliation: Curriculum in Genetics and Molecular Biology.
authors.forename: Glenn G
authors.initials: GG
authors.lastname: Wozniak
authors.affiliation: Curriculum in Genetics and Molecular Biology, Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA brian_strahl@med.unc.edu.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Strahl
mesh_terms: D002384:Catalysis; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000378:metabolism*; D055550:Protein Stability; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D035181:TATA-Box Binding Protein / Q000378:metabolism; D054875:Ubiquitination
chemical_list: C472168:Bre1 protein, S cerevisiae; D006657:Histones; C107273:RTF1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D035181:TATA-Box Binding Protein
keywords: chromatin; gene transcription; histones; ubiquitylation
references.citation: Nature. 2002 Jul 4;418(6893):104-8
references.pmid: 12077605
references.citation: Mol Cell. 2005 Feb 18;17(4):585-94
references.pmid: 15721261
references.citation: Science. 2000 Jan 21;287(5452):501-4
references.pmid: 10642555
references.citation: J Biol Chem. 2002 Sep 20;277(38):34655-7
references.pmid: 12167634
references.citation: Yeast. 2004 Aug;21(11):947-62
references.pmid: 15334558
references.citation: J Biol Chem. 2003 Sep 12;278(37):34739-42
references.pmid: 12876294
references.citation: Biochim Biophys Acta. 2014 Dec;1839(12):1353-61
references.pmid: 24631869
references.citation: Cell. 2007 Dec 14;131(6):1084-96
references.pmid: 18083099
references.citation: Cell. 2011 Sep 2;146(5):709-19
references.pmid: 21884933
references.citation: Nat Cell Biol. 2008 Nov;10(11):1365-71
references.pmid: 18849979
references.citation: Nature. 2002 Aug 1;418(6897):498
references.pmid: 12152067
references.citation: J Biol Chem. 2009 Jul 31;284(31):20582-92
references.pmid: 19531475
references.citation: Nat Struct Mol Biol. 2013 Mar;20(3):259-66
references.pmid: 23463310
references.citation: Cell. 2007 Feb 23;128(4):693-705
references.pmid: 17320507
references.citation: Nat Chem Biol. 2011 Feb;7(2):113-9
references.pmid: 21196936
references.citation: Genes Dev. 2004 Jan 15;18(2):184-95
references.pmid: 14752010
references.citation: J Biol Chem. 2010 Apr 9;285(15):11704-13
references.pmid: 20139424
references.citation: Nat Commun. 2014 Jun 09;5:3965
references.pmid: 24910128
references.citation: Genetics. 2012 Oct;192(2):371-84
references.pmid: 22851644
references.citation: Mol Cell. 2013 Mar 28;49(6):1121-33
references.pmid: 23453808
references.citation: Mol Cell. 2012 Dec 14;48(5):734-46
references.pmid: 23103252
references.citation: J Biol Chem. 2010 Dec 17;285(51):39855-65
references.pmid: 20952395
references.citation: Mol Cell. 2003 Jan;11(1):261-6
references.pmid: 12535538
references.citation: Genes Dev. 2003 Nov 1;17(21):2648-63
references.pmid: 14563679
references.citation: Mol Cell Biol. 2005 Jan;25(2):637-51
references.pmid: 15632065
references.citation: DNA Repair (Amst). 2009 Apr 5;8(4):470-82
references.pmid: 19230796
references.citation: Proc Natl Acad Sci U S A. 2012 Jul 3;109(27):10837-42
references.pmid: 22699496
references.citation: Biochim Biophys Acta. 2010 May-Jun;1799(5-6):379-88
references.pmid: 20060942
references.citation: Nature. 2008 Jun 5;453(7196):812-6
references.pmid: 18449190
references.citation: Biochemistry. 1997 Nov 25;36(47):14418-29
references.pmid: 9398160
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 29;106(39):16686-91
references.pmid: 19805358
references.citation: Cell. 2006 May 19;125(4):703-17
references.pmid: 16713563
references.citation: Epigenetics. 2010 Aug 16;5(6):460-8
references.pmid: 20523115
references.citation: Genes Dev. 2007 Aug 15;21(16):2018-29
references.pmid: 17675446
references.citation: J Biol Chem. 2002 Aug 9;277(32):28368-71
references.pmid: 12070136
references.citation: Mol Cell Biol. 2010 Jul;30(14):3635-45
references.pmid: 20498280
references.citation: J Biol Chem. 2003 Sep 5;278(36):33625-8
references.pmid: 12876293
references.citation: Mol Cell. 2008 Jul 11;31(1):57-66
references.pmid: 18614047
references.citation: Mol Cell. 2003 Jan;11(1):267-74
references.pmid: 12535539