Chemical-genomic dissection of the CTD code.
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.
Tietjen
Joshua R
JR
Department of Biochemistry and The Genome Center, University of Wisconsin, Madison, Wisconsin, USA.
Zhang
David W
DW
Rodríguez-Molina
Juan B
JB
White
Brent E
BE
Akhtar
Md Sohail
MS
Heidemann
Martin
M
Li
Xin
X
Chapman
Rob D
RD
Shokat
Kevan
K
Keles
Sündüz
S
Eick
Dirk
D
Ansari
Aseem Z
AZ
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
D022661:RNA, Untranslated; D017346:Protein Serine-Threonine Kinases; D012319:RNA Polymerase II
Proc Natl Acad Sci U S A. 2009 Apr 28;106(17):6956-61
19365074
Mol Cell. 2009 Mar 27;33(6):752-62
19328068
Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2346-9
15687503
Science. 2007 Dec 14;318(5857):1735-6
18079391
EMBO J. 2007 Nov 14;26(22):4646-56
17948059
Cell Cycle. 2006 May;5(10):1066-8
16721054
Cell. 2002 Feb 22;108(4):501-12
11909521
Nat Struct Biol. 2003 Sep;10(9):679-80
12942140
EMBO J. 2005 Dec 7;24(23):4154-65
16308568
Cell. 2005 Nov 18;123(4):581-92
16286007
Gene Expr. 2000;9(1-2):3-13
11097421
Mol Cell Biol. 2003 Oct;23(19):7005-18
12972617
Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):5812-7
17392431
Nature. 1993 May 27;363(6427):371-4
8497323
Curr Opin Cell Biol. 2008 Jun;20(3):334-40
18513937
Science. 2001 Aug 10;293(5532):1074-80
11498575
J Biol Chem. 1999 Sep 24;274(39):27823-8
10488128
Genes Dev. 2000 Oct 1;14(19):2435-40
11018011
Mol Cell Biol. 2009 Sep;29(17):4852-63
19581288
Nature. 2009 Feb 19;457(7232):1033-7
19169243
Mol Cell. 2009 Oct 23;36(2):178-91
19854129
Mol Cell. 2003 Mar;11(3):709-19
12667453
Chem Biol. 2005 Jun;12(6):621-37
15975507
Mol Cell. 2005 Oct 28;20(2):225-36
16246725
Mol Cell. 2006 Sep 15;23(6):853-64
16973437
Yeast. 2000 Jan 15;16(1):57-64
10620775
Mol Cell. 2009 Nov 25;36(4):541-6
19941815
Mol Cell. 2002 May;9(5):1101-11
12049745
Annu Rev Biochem. 2000;69:729-49
10966474
Nature. 2009 Feb 19;457(7232):1038-42
19169244
Mol Cell. 2006 Sep 15;23(6):841-51
16973436
Nat Genet. 2007 Oct;39(10):1235-44
17873876
Annu Rev Genet. 2000;34:77-137
11092823
Mol Cell Biol. 2004 Feb;24(4):1721-35
14749387
Mol Cell. 2004 May 7;14(3):387-94
15125841
Nature. 2001 Sep 20;413(6853):327-31
11565036
Genes Dev. 2006 Nov 1;20(21):2922-36
17079683
Science. 2007 Dec 14;318(5857):1780-2
18079404
Mol Cell. 2004 Jan 16;13(1):67-76
14731395
Science. 2007 Dec 14;318(5857):1777-9
18079403
Genes Dev. 2004 Oct 15;18(20):2437-68
15489290
Mol Cell. 2009 Mar 27;33(6):738-51
19328067
Mol Cell. 2006 Dec 8;24(5):735-746
17157256
Genome Res. 2009 Mar;19(3):360-71
19124666
Cell. 1998 Nov 25;95(5):717-28
9845373
Genes Dev. 2006 Mar 1;20(5):601-12
16510875
EMBO J. 2009 Feb 4;28(3):205-12
19131970
Mol Cell Biol. 2003 Jun;23(12):4207-18
12773564
Mol Cell. 2009 Apr 24;34(2):168-78
19394294
Genes Dev. 2000 Oct 1;14(19):2452-60
11018013
Mol Cell. 2009 May 15;34(3):387-93
19450536
Mol Cell Biol. 2009 Oct;29(20):5455-64
19667075
Cell. 2005 Oct 21;123(2):265-76
16239144
Mol Biol Cell. 2005 Jun;16(6):2734-45
15829570
J Biol Chem. 2007 May 11;282(19):14113-20
17376774
J Biol Chem. 2009 Sep 25;284(39):26421-6
19679665
Mol Cell. 2006 Dec 8;24(5):723-734
17157255
RNA. 2004 Oct;10(10):1489-98
15383674
Nature. 2004 Sep 2;431(7004):99-104
15343339
Trends Genet. 2008 Jun;24(6):280-8
18457900
Genes Dev. 2001 Dec 15;15(24):3319-29
11751637