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.
Vyšlo v časopise:
Transcription Initiation Patterns Indicate Divergent Strategies for Gene Regulation at the Chromatin Level. PLoS Genet 7(1): e32767. doi:10.1371/journal.pgen.1001274
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1001274
Souhrn
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.
Zdroje
1. CarninciP
SandelinA
LenhardB
KatayamaS
ShimokawaK
2006 Genome-wide analysis of mammalian promoter architecture and evolution. Nat Genet 38 626 635
2. NiT
CorcoranDL
RachEA
SongS
SpanaEP
2010 A paired-end sequencing strategy to map the complex landscape of transcription initiation. Nat Methods 7 521 527
3. Juven-GershonT
KadonagaJT
2010 Regulation of gene expression via the core promoter and the basal transcriptional machinery. Dev Biol 339 225 229
4. OhlerU
WassarmanDA
2010 Promoting developmental transcription. Development 137 15 26
5. NechaevS
FargoDC
Dos SantosG
LiuL
GaoY
2009 Global Analysis of Short RNAs Reveals Widespread Promoter-Proximal Stalling and Arrest of Pol II in Drosophila. Science 327 335 338
6. MavrichTN
JiangC
IoshikhesIP
LiX
VentersBJ
2008 Nucleosome organization in the Drosophila genome. Nature 453 358 362
7. SchonesDE
CuiK
CuddapahS
RohTY
BarskiA
2008 Dynamic regulation of nucleosome positioning in the human genome. Cell 132 887 898
8. JinC
ZangC
WeiG
CuiK
PengW
2009 H3.3/H2A.Z double variant-containing nucleosomes mark ‘nucleosome-free regions’ of active promoters and other regulatory regions. Nat Genet 41 941 945
9. RaisnerRM
HartleyPD
MeneghiniMD
BaoMZ
LiuCL
2005 Histone variant H2A.Z marks the 5′ ends of both active and inactive genes in euchromatin. Cell 123 233 248
10. BarskiA
CuddapahS
CuiK
RohTY
SchonesDE
2007 High-resolution profiling of histone methylations in the human genome. Cell 129 823 837
11. TsukiyamaT
BeckerPB
WuC
1994 ATP-dependent nucleosome disruption at a heat-shock promoter mediated by binding of GAGA transcription factor. Nature 367 525 532
12. FuY
SinhaM
PetersonCL
WengZ
2008 The insulator binding protein CTCF positions 20 nucleosomes around its binding sites across the human genome. PLoS Genet 4 e1000138doi:10.1371/journal.pgen.1000138
13. IoshikhesIP
AlbertI
ZantonSJ
PughBF
2006 Nucleosome positions predicted through comparative genomics. Nat Genet 38 1210 1215
14. EngstromPG
Ho SuiSJ
DrivenesO
BeckerTS
LenhardB
2007 Genomic regulatory blocks underlie extensive microsynteny conservation in insects. Genome Res 17 1898 1908
15. GanapathiM
SrivastavaP
Das SutarSK
KumarK
DasguptaD
2005 Comparative analysis of chromatin landscape in regulatory regions of human housekeeping and tissue specific genes. BMC Bioinformatics 6 126
16. OhlerU
2006 Identification of core promoter modules in Drosophila and their application in accurate transcription start site prediction. Nucleic Acids Res 34 5943 5950
17. SaxonovS
BergP
BrutlagDL
2006 A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U S A 103 1412 1417
18. TilloD
KaplanN
MooreIK
Fondufe-MittendorfY
GossettAJ
2010 High nucleosome occupancy is encoded at human regulatory sequences. PLoS ONE 5 e9129doi:10.1371/journal.pone.0009129
19. PongerL
DuretL
MouchiroudD
2001 Determinants of CpG islands: expression in early embryo and isochore structure. Genome Res 11 1854 1860
20. Ramirez-CarrozziVR
BraasD
BhattDM
ChengCS
HongC
2009 A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling. Cell 138 114 128
21. TiroshI
BarkaiN
2008 Two strategies for gene regulation by promoter nucleosomes. Genome Res 18 1084 1091
22. NegreN
BrownCD
ShahPK
KheradpourP
MorrisonCA
2010 A comprehensive map of insulator elements for the Drosophila genome. PLoS Genet 6 e1000814doi:10.1371/journal.pgen.1000814
23. RachEA
YuanHY
MajorosWH
TomancakP
OhlerU
2009 Motif composition, conservation and condition-specificity of single and alternative transcription start sites in the Drosophila genome. Genome Biol 10 R73
24. DaveyC
PenningsS
AllanJ
1997 CpG methylation remodels chromatin structure in vitro. J Mol Biol 267 276 288
25. DaveyCS
PenningsS
ReillyC
MeehanRR
AllanJ
2004 A determining influence for CpG dinucleotides on nucleosome positioning in vitro. Nucleic Acids Res 32 4322 4331
26. KawajiH
SeverinJ
LizioM
WaterhouseA
KatayamaS
2009 The FANTOM web resource: from mammalian transcriptional landscape to its dynamic regulation. Genome Biol 10 R40
27. TolstorukovMY
KharchenkoPV
GoldmanJA
KingstonRE
ParkPJ
2009 Comparative analysis of H2A.Z nucleosome organization in the human and yeast genomes. Genome Res 19 967 977
28. BoyleAP
DavisS
ShulhaHP
MeltzerP
MarguliesEH
2008 High-resolution mapping and characterization of open chromatin across the genome. Cell 132 311 322
29. WangX
XuanZ
ZhaoX
LiY
ZhangMQ
2009 High-resolution human core-promoter prediction with CoreBoost_HM. Genome Res 19 266 275
30. TakaiD
JonesPA
2002 Comprehensive analysis of CpG islands in human chromosomes 21 and 22. Proc Natl Acad Sci U S A 99 3740 3745
31. WangZ
ZangC
RosenfeldJA
SchonesDE
BarskiA
2008 Combinatorial patterns of histone acetylations and methylations in the human genome. Nat Genet 40 897 903
32. SpiesN
NielsenCB
PadgettRA
BurgeCB
2009 Biased chromatin signatures around polyadenylation sites and exons. Mol Cell 36 245 254
33. MegrawM
PereiraF
JensenST
OhlerU
HatzigeorgiouAG
2009 A transcription factor affinity-based code for mammalian transcription initiation. Genome Res 19 644 656
34. KaplanN
MooreIK
Fondufe-MittendorfY
GossettAJ
TilloD
2009 The DNA-encoded nucleosome organization of a eukaryotic genome. Nature 458 362 366
35. AlbertI
MavrichTN
TomshoLP
QiJ
ZantonSJ
2007 Translational and rotational settings of H2A.Z nucleosomes across the Saccharomyces cerevisiae genome. Nature 446 572 576
36. ParryTJ
TheisenJW
HsuJY
WangYL
CorcoranDL
2010 The TCT motif, a key component of an RNA polymerase II transcription system for the translational machinery. Genes Dev 24 2013 2018
37. FitzGeraldPC
SturgillD
ShyakhtenkoA
OliverB
VinsonC
2006 Comparative genomics of Drosophila and human core promoters. Genome Biol 7 R53
38. ZeitlingerJ
StarkA
KellisM
HongJW
NechaevS
2007 RNA polymerase stalling at developmental control genes in the Drosophila melanogaster embryo. Nat Genet 39 1512 1516
39. RahlPB
LinCY
SeilaAC
FlynnRA
McCuineS
2010 c-Myc regulates transcriptional pause release. Cell 141 432 445
40. SmithST
WickramasingheP
OlsonA
LoukinovD
LinL
2009 Genome wide ChIP-chip analyses reveal important roles for CTCF in Drosophila genome organization. Dev Biol 328 518 528
41. ChernukhinI
ShamsuddinS
KangSY
BergstromR
KwonYW
2007 CTCF interacts with and recruits the largest subunit of RNA polymerase II to CTCF target sites genome-wide. Mol Cell Biol 27 1631 1648
42. CelnikerSE
DillonLA
GersteinMB
GunsalusKC
HenikoffS
2009 Unlocking the secrets of the genome. Nature 459 927 930
43. MahmoudiT
KatsaniKR
VerrijzerCP
2002 GAGA can mediate enhancer function in trans by linking two separate DNA molecules. Embo J 21 1775 1781
44. LisJ
1998 Promoter-associated pausing in promoter architecture and postinitiation transcriptional regulation. Cold Spring Harb Symp Quant Biol 63 347 356
45. KratzA
ArnerE
SaitoR
KubosakiA
KawaiJ
2010 Core promoter structure and genomic context reflect histone 3 lysine 9 acetylation patterns. BMC Genomics 11 257
46. AdkinsNL
HagermanTA
GeorgelP
2006 GAGA protein: a multi-faceted transcription factor. Biochem Cell Biol 84 559 567
47. KatsaniKR
HajibagheriMA
VerrijzerCP
1999 Co-operative DNA binding by GAGA transcription factor requires the conserved BTB/POZ domain and reorganizes promoter topology. Embo J 18 698 708
48. HendrixDA
HongJW
ZeitlingerJ
RokhsarDS
LevineMS
2008 Promoter elements associated with RNA Pol II stalling in the Drosophila embryo. Proc Natl Acad Sci U S A 105 7762 7767
49. CairnsBR
2009 The logic of chromatin architecture and remodelling at promoters. Nature 461 193 198
50. ZhangY
MoqtaderiZ
RattnerBP
EuskirchenG
SnyderM
2009 Intrinsic histone-DNA interactions are not the major determinant of nucleosome positions in vivo. Nat Struct Mol Biol 16 847 852
51. HenikoffS
AhmadK
2005 Assembly of variant histones into chromatin. Annu Rev Cell Dev Biol 21 133 153
52. MitoY
HenikoffJG
HenikoffS
2007 Histone replacement marks the boundaries of cis-regulatory domains. Science 315 1408 1411
53. TiroshI
BarkaiN
VerstrepenKJ
2009 Promoter architecture and the evolvability of gene expression. J Biol 8 95
54. BernsteinBE
MeissnerA
LanderES
2007 The mammalian epigenome. Cell 128 669 681
55. WilsonRJ
GoodmanJL
StreletsVB
Flybase Consortium 2008 FlyBase: integration and improvements to query tools. Nucleic Acids Research 36 D588 D592
56. ManakJR
DikeS
SementchenkoV
KapranovP
BiemarF
2006 Biological function of unannotated transcription during the early development of Drosophila melanogaster. Nat Genet 38 1151 1158
57. Gardiner-GardenM
FrommerM
1987 CpG islands in vertebrate genomes. J Mol Biol 196 261 282
58. Portales-CasamarE
ThongjueaS
KwonAT
ArenillasD
ZhaoX
2010 JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles. Nucleic Acids Res 38 D105 110
59. KohK
KimS-J
BoydS
2007 An interior-point method for large-scale L1-regularized ligistric regression. J Mach Learn Res 8 1519 1555
60. HochheimerA
ZhouS
ZhengS
HolmesMC
TjianR
2002 TRF2 associates with DREF and directs promoter-selective gene expression in Drosophila. Nature 420 439 445
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Genetika Reprodukčná medicínaČlánok vyšiel v časopise
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