Transcription initiation patterns indicate divergent strategies for gene regulation at the chromatin level.
The application of deep sequencing to map 5' capped transcripts has confirmed the existence of at least two distinct promoter classes in metazoans: "focused" promoters with transcription start sites (TSSs) that occur in a narrowly defined genomic span and "dispersed" promoters with TSSs that are spread over a larger window. Previous studies have explored the presence of genomic features, such as CpG islands and sequence motifs, in these promoter classes, but virtually no studies have directly investigated the relationship with chromatin features. Here, we show that promoter classes are significantly differentiated by nucleosome organization and chromatin structure. Dispersed promoters display higher associations with well-positioned nucleosomes downstream of the TSS and a more clearly defined nucleosome free region upstream, while focused promoters have a less organized nucleosome structure, yet higher presence of RNA polymerase II. These differences extend to histone variants (H2A.Z) and marks (H3K4 methylation), as well as insulator binding (such as CTCF), independent of the expression levels of affected genes. Notably, differences are conserved across mammals and flies, and they provide for a clearer separation of promoter architectures than the presence and absence of CpG islands or the occurrence of stalled RNA polymerase. Computational models support the stronger contribution of chromatin features to the definition of dispersed promoters compared to focused start sites. Our results show that promoter classes defined from 5' capped transcripts not only reflect differences in the initiation process at the core promoter but also are indicative of divergent transcriptional programs established within gene-proximal nucleosome organization.
Program in Computational Biology and Bioinformatics, Duke University, Durham, North Carolina, United States of America.
Elizabeth A
EA
Rach
Deborah R
DR
Winter
Ashlee M
AM
Benjamin
David L
DL
Corcoran
Ting
T
Ni
Jun
J
Zhu
Uwe
U
Ohler
D000818:Animals; D002843:Chromatin; D018899:CpG Islands; D004331:Drosophila melanogaster / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D011401:Promoter Regions, Genetic; D014158:Transcription, Genetic
D002843:Chromatin
Dev Biol. 2010 Mar 15;339(2):225-9
19682982
PLoS Genet. 2008 Jul 25;4(7):e1000138
18654629
Nature. 2009 Mar 19;458(7236):362-6
19092803
Nat Methods. 2010 Jul;7(7):521-7
20495556
Genome Biol. 2009;10(7):R73
19589141
Genome Biol. 2009;10(4):R40
19374775
Biochem Cell Biol. 2006 Aug;84(4):559-67
16936828
Nat Genet. 2008 Jul;40(7):897-903
18552846
Nature. 1994 Feb 10;367(6463):525-32
8107823
Nucleic Acids Res. 2008 Jan;36(Database issue):D588-93
18160408
Nat Genet. 2009 Aug;41(8):941-5
19633671
Cell. 2010 Apr 30;141(3):432-45
20434984
Mol Cell. 2009 Oct 23;36(2):245-54
19854133
Cold Spring Harb Symp Quant Biol. 1998;63:347-56
10384299
Genome Res. 2007 Dec;17(12):1898-908
17989259
Genome Res. 2001 Nov;11(11):1854-60
11691850
Proc Natl Acad Sci U S A. 2008 Jun 3;105(22):7762-7
18505835
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3740-5
11891299
Nature. 2007 Mar 29;446(7135):572-6
17392789
Nature. 2009 Sep 10;461(7261):193-8
19741699
J Mol Biol. 1997 Mar 28;267(2):276-88
9096225
EMBO J. 1999 Feb 1;18(3):698-708
9927429
Genome Biol. 2006;7(7):R53
16827941
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1412-7
16432200
Science. 2007 Mar 9;315(5817):1408-11
17347439
EMBO J. 2002 Apr 2;21(7):1775-81
11927561
Nature. 2009 Jun 18;459(7249):927-30
19536255
Nat Genet. 2006 Jun;38(6):626-35
16645617
Nucleic Acids Res. 2004 Aug 13;32(14):4322-31
15310836
Annu Rev Cell Dev Biol. 2005;21:133-53
16212490
PLoS Genet. 2010 Jan 15;6(1):e1000814
20084099
Nat Genet. 2007 Dec;39(12):1512-6
17994019
Nucleic Acids Res. 2006;34(20):5943-50
17068082
Nucleic Acids Res. 2010 Jan;38(Database issue):D105-10
19906716
Cell. 2007 May 18;129(4):823-37
17512414
Dev Biol. 2009 Apr 15;328(2):518-28
19210964
BMC Bioinformatics. 2005 May 26;6:126
15918906
Nat Struct Mol Biol. 2009 Aug;16(8):847-52
19620965
Cell. 2008 Mar 7;132(5):887-98
18329373
Genome Res. 2009 Jun;19(6):967-77
19246569
Nature. 2002 Nov 28;420(6914):439-45
12459787
Genome Res. 2008 Jul;18(7):1084-91
18448704
Science. 2010 Jan 15;327(5963):335-8
20007866
Cell. 2007 Feb 23;128(4):669-81
17320505
Genome Res. 2009 Apr;19(4):644-56
19141595
BMC Genomics. 2010 Apr 21;11:257
20409305
J Mol Biol. 1987 Jul 20;196(2):261-82
3656447
J Biol. 2009;8(11):95
20017897
Nat Genet. 2006 Oct;38(10):1210-5
16964265
Genes Dev. 2010 Sep 15;24(18):2013-8
20801935
Cell. 2005 Oct 21;123(2):233-48
16239142
Cell. 2009 Jul 10;138(1):114-28
19596239
Nature. 2008 May 15;453(7193):358-62
18408708
PLoS One. 2010 Feb 09;5(2):e9129
20161746
Mol Cell Biol. 2007 Mar;27(5):1631-48
17210645
Development. 2010 Jan;137(1):15-26
20023156
Cell. 2008 Jan 25;132(2):311-22
18243105
Nat Genet. 2006 Oct;38(10):1151-8
16951679
Genome Res. 2009 Feb;19(2):266-75
18997002