title: Chemical-genomic dissection of the CTD code.
abstract: Sequential modifications of the RNA polymerase II (Pol II) C-terminal domain (CTD) coordinate the stage-specific association and release of cellular machines during transcription. Here we examine the genome-wide distributions of the 'early' (phospho-Ser5 (Ser5-P)), 'mid' (Ser7-P) and 'late' (Ser2-P) CTD marks. We identify gene class-specific patterns and find widespread co-occurrence of the CTD marks. Contrary to its role in 3'-processing of noncoding RNA, the Ser7-P marks are placed early and retained until transcription termination at all Pol II-dependent genes. Chemical-genomic analysis reveals that the promoter-distal Ser7-P marks are not remnants of early phosphorylation but are placed anew by the CTD kinase Bur1. Consistent with the ability of Bur1 to facilitate transcription elongation and suppress cryptic transcription, high levels of Ser7-P are observed at highly transcribed genes. We propose that Ser7-P could facilitate elongation and suppress cryptic transcription.
authors.affiliation: Department of Biochemistry and The Genome Center, University of Wisconsin, Madison, Wisconsin, USA.
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Tietjen
authors.forename: David W
authors.initials: DW
authors.lastname: Zhang
authors.forename: Juan B
authors.initials: JB
authors.lastname: Rodríguez-Molina
authors.forename: Brent E
authors.initials: BE
authors.lastname: White
authors.forename: Md Sohail
authors.initials: MS
authors.lastname: Akhtar
authors.forename: Martin
authors.initials: M
authors.lastname: Heidemann
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Rob D
authors.initials: RD
authors.lastname: Chapman
authors.forename: Kevan
authors.initials: K
authors.lastname: Shokat
authors.forename: Sündüz
authors.initials: S
authors.lastname: Keles
authors.forename: Dirk
authors.initials: D
authors.lastname: Eick
authors.forename: Aseem Z
authors.initials: AZ
authors.lastname: Ansari
mesh_terms: D016678:Genome; D005810:Multigene Family; D016366:Open Reading Frames; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D022661:RNA, Untranslated; D013379:Substrate Specificity; D014158:Transcription, Genetic
chemical_list: D022661:RNA, Untranslated; D017346:Protein Serine-Threonine Kinases; D012319:RNA Polymerase II
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):6956-61
references.pmid: 19365074
references.citation: Mol Cell. 2009 Mar 27;33(6):752-62
references.pmid: 19328068
references.citation: Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2346-9
references.pmid: 15687503
references.citation: Science. 2007 Dec 14;318(5857):1735-6
references.pmid: 18079391
references.citation: EMBO J. 2007 Nov 14;26(22):4646-56
references.pmid: 17948059
references.citation: Cell Cycle. 2006 May;5(10):1066-8
references.pmid: 16721054
references.citation: Cell. 2002 Feb 22;108(4):501-12
references.pmid: 11909521
references.citation: Nat Struct Biol. 2003 Sep;10(9):679-80
references.pmid: 12942140
references.citation: EMBO J. 2005 Dec 7;24(23):4154-65
references.pmid: 16308568
references.citation: Cell. 2005 Nov 18;123(4):581-92
references.pmid: 16286007
references.citation: Gene Expr. 2000;9(1-2):3-13
references.pmid: 11097421
references.citation: Mol Cell Biol. 2003 Oct;23(19):7005-18
references.pmid: 12972617
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5812-7
references.pmid: 17392431
references.citation: Nature. 1993 May 27;363(6427):371-4
references.pmid: 8497323
references.citation: Curr Opin Cell Biol. 2008 Jun;20(3):334-40
references.pmid: 18513937
references.citation: Science. 2001 Aug 10;293(5532):1074-80
references.pmid: 11498575
references.citation: J Biol Chem. 1999 Sep 24;274(39):27823-8
references.pmid: 10488128
references.citation: Genes Dev. 2000 Oct 1;14(19):2435-40
references.pmid: 11018011
references.citation: Mol Cell Biol. 2009 Sep;29(17):4852-63
references.pmid: 19581288
references.citation: Nature. 2009 Feb 19;457(7232):1033-7
references.pmid: 19169243
references.citation: Mol Cell. 2009 Oct 23;36(2):178-91
references.pmid: 19854129
references.citation: Mol Cell. 2003 Mar;11(3):709-19
references.pmid: 12667453
references.citation: Chem Biol. 2005 Jun;12(6):621-37
references.pmid: 15975507
references.citation: Mol Cell. 2005 Oct 28;20(2):225-36
references.pmid: 16246725
references.citation: Mol Cell. 2006 Sep 15;23(6):853-64
references.pmid: 16973437
references.citation: Yeast. 2000 Jan 15;16(1):57-64
references.pmid: 10620775
references.citation: Mol Cell. 2009 Nov 25;36(4):541-6
references.pmid: 19941815
references.citation: Mol Cell. 2002 May;9(5):1101-11
references.pmid: 12049745
references.citation: Annu Rev Biochem. 2000;69:729-49
references.pmid: 10966474
references.citation: Nature. 2009 Feb 19;457(7232):1038-42
references.pmid: 19169244
references.citation: Mol Cell. 2006 Sep 15;23(6):841-51
references.pmid: 16973436
references.citation: Nat Genet. 2007 Oct;39(10):1235-44
references.pmid: 17873876
references.citation: Annu Rev Genet. 2000;34:77-137
references.pmid: 11092823
references.citation: Mol Cell Biol. 2004 Feb;24(4):1721-35
references.pmid: 14749387
references.citation: Mol Cell. 2004 May 7;14(3):387-94
references.pmid: 15125841
references.citation: Nature. 2001 Sep 20;413(6853):327-31
references.pmid: 11565036
references.citation: Genes Dev. 2006 Nov 1;20(21):2922-36
references.pmid: 17079683
references.citation: Science. 2007 Dec 14;318(5857):1780-2
references.pmid: 18079404
references.citation: Mol Cell. 2004 Jan 16;13(1):67-76
references.pmid: 14731395
references.citation: Science. 2007 Dec 14;318(5857):1777-9
references.pmid: 18079403
references.citation: Genes Dev. 2004 Oct 15;18(20):2437-68
references.pmid: 15489290
references.citation: Mol Cell. 2009 Mar 27;33(6):738-51
references.pmid: 19328067
references.citation: Mol Cell. 2006 Dec 8;24(5):735-746
references.pmid: 17157256
references.citation: Genome Res. 2009 Mar;19(3):360-71
references.pmid: 19124666
references.citation: Cell. 1998 Nov 25;95(5):717-28
references.pmid: 9845373
references.citation: Genes Dev. 2006 Mar 1;20(5):601-12
references.pmid: 16510875
references.citation: EMBO J. 2009 Feb 4;28(3):205-12
references.pmid: 19131970
references.citation: Mol Cell Biol. 2003 Jun;23(12):4207-18
references.pmid: 12773564
references.citation: Mol Cell. 2009 Apr 24;34(2):168-78
references.pmid: 19394294
references.citation: Genes Dev. 2000 Oct 1;14(19):2452-60
references.pmid: 11018013
references.citation: Mol Cell. 2009 May 15;34(3):387-93
references.pmid: 19450536
references.citation: Mol Cell Biol. 2009 Oct;29(20):5455-64
references.pmid: 19667075
references.citation: Cell. 2005 Oct 21;123(2):265-76
references.pmid: 16239144
references.citation: Mol Biol Cell. 2005 Jun;16(6):2734-45
references.pmid: 15829570
references.citation: J Biol Chem. 2007 May 11;282(19):14113-20
references.pmid: 17376774
references.citation: J Biol Chem. 2009 Sep 25;284(39):26421-6
references.pmid: 19679665
references.citation: Mol Cell. 2006 Dec 8;24(5):723-734
references.pmid: 17157255
references.citation: RNA. 2004 Oct;10(10):1489-98
references.pmid: 15383674
references.citation: Nature. 2004 Sep 2;431(7004):99-104
references.pmid: 15343339
references.citation: Trends Genet. 2008 Jun;24(6):280-8
references.pmid: 18457900
references.citation: Genes Dev. 2001 Dec 15;15(24):3319-29
references.pmid: 11751637