#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

A Comprehensive Map of Insulator Elements for the Genome


Insulators are DNA sequences that control the interactions among genomic regulatory elements and act as chromatin boundaries. A thorough understanding of their location and function is necessary to address the complexities of metazoan gene regulation. We studied by ChIP–chip the genome-wide binding sites of 6 insulator-associated proteins—dCTCF, CP190, BEAF-32, Su(Hw), Mod(mdg4), and GAF—to obtain the first comprehensive map of insulator elements in Drosophila embryos. We identify over 14,000 putative insulators, including all classically defined insulators. We find two major classes of insulators defined by dCTCF/CP190/BEAF-32 and Su(Hw), respectively. Distributional analyses of insulators revealed that particular sub-classes of insulator elements are excluded between cis-regulatory elements and their target promoters; divide differentially expressed, alternative, and divergent promoters; act as chromatin boundaries; are associated with chromosomal breakpoints among species; and are embedded within active chromatin domains. Together, these results provide a map demarcating the boundaries of gene regulatory units and a framework for understanding insulator function during the development and evolution of Drosophila.


Vyšlo v časopise: A Comprehensive Map of Insulator Elements for the Genome. PLoS Genet 6(1): e32767. doi:10.1371/journal.pgen.1000814
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1000814

Souhrn

Insulators are DNA sequences that control the interactions among genomic regulatory elements and act as chromatin boundaries. A thorough understanding of their location and function is necessary to address the complexities of metazoan gene regulation. We studied by ChIP–chip the genome-wide binding sites of 6 insulator-associated proteins—dCTCF, CP190, BEAF-32, Su(Hw), Mod(mdg4), and GAF—to obtain the first comprehensive map of insulator elements in Drosophila embryos. We identify over 14,000 putative insulators, including all classically defined insulators. We find two major classes of insulators defined by dCTCF/CP190/BEAF-32 and Su(Hw), respectively. Distributional analyses of insulators revealed that particular sub-classes of insulator elements are excluded between cis-regulatory elements and their target promoters; divide differentially expressed, alternative, and divergent promoters; act as chromatin boundaries; are associated with chromosomal breakpoints among species; and are embedded within active chromatin domains. Together, these results provide a map demarcating the boundaries of gene regulatory units and a framework for understanding insulator function during the development and evolution of Drosophila.


Zdroje

1. KellumR

SchedlP

1991 A position-effect assay for boundaries of higher order chromosomal domains. Cell 64 941 950

2. KellumR

SchedlP

1992 A group of scs elements function as domain boundaries in an enhancer-blocking assay. Mol Cell Biol 12 2424 2431

3. HoldridgeC

DorsettD

1991 Repression of hsp70 heat shock gene transcription by the suppressor of hairy-wing protein of Drosophila melanogaster. Mol Cell Biol 11 1894 1900

4. GeyerPK

CorcesVG

1992 DNA position-specific repression of transcription by a Drosophila zinc finger protein. Genes Dev 6 1865 1873

5. WallaceJA

FelsenfeldG

2007 We gather together: insulators and genome organization. Curr Opin Genet Dev 17 400 407

6. ChungJH

WhiteleyM

FelsenfeldG

1993 A 5′ element of the chicken beta-globin domain serves as an insulator in human erythroid cells and protects against position effect in Drosophila. Cell 74 505 514

7. BellAC

WestAG

FelsenfeldG

1999 The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell 98 387 396

8. MoonH

FilippovaG

LoukinovD

PugachevaE

ChenQ

2005 CTCF is conserved from Drosophila to humans and confers enhancer blocking of the Fab-8 insulator. EMBO Rep 6 165 170

9. CiavattaD

RogersS

MagnusonT

2007 Drosophila CTCF is required for Fab-8 enhancer blocking activity in S2 cells. J Mol Biol 373 233 239

10. HolohanEE

KwongC

AdryanB

BartkuhnM

HeroldM

2007 CTCF genomic binding sites in Drosophila and the organisation of the bithorax complex. PLoS Genet 3 e112 doi:10.1371/journal.pgen.0030112

11. MohanM

BartkuhnM

HeroldM

PhilippenA

HeinlN

2007 The Drosophila insulator proteins CTCF and CP190 link enhancer blocking to body patterning. EMBO J 26 4203 4214

12. GolovninA

BiryukovaI

RomanovaO

SilichevaM

ParshikovA

2003 An endogenous Su(Hw) insulator separates the yellow gene from the Achaete-scute gene complex in Drosophila. Development 130 3249 3258

13. ParnellTJ

VieringMM

SkjesolA

HelouC

KuhnEJ

2003 An endogenous suppressor of hairy-wing insulator separates regulatory domains in Drosophila. Proc Natl Acad Sci U S A 100 13436 13441

14. AdryanB

WoerfelG

Birch-MachinI

GaoS

QuickM

2007 Genomic mapping of Suppressor of Hairy-wing binding sites in Drosophila. Genome Biol 8 R167

15. GauseM

MorcilloP

DorsettD

2001 Insulation of enhancer-promoter communication by a gypsy transposon insert in the Drosophila cut gene: cooperation between suppressor of hairy-wing and modifier of mdg4 proteins. Mol Cell Biol 21 4807 4817

16. GhoshD

GerasimovaTI

CorcesVG

2001 Interactions between the Su(Hw) and Mod(mdg4) proteins required for gypsy insulator function. EMBO J 20 2518 2527

17. PaiCY

LeiEP

GhoshD

CorcesVG

2004 The centrosomal protein CP190 is a component of the gypsy chromatin insulator. Mol Cell 16 737 748

18. ZhaoK

HartCM

LaemmliUK

1995 Visualization of chromosomal domains with boundary element-associated factor BEAF-32. Cell 81 879 889

19. GasznerM

VazquezJ

SchedlP

1999 The Zw5 protein, a component of the scs chromatin domain boundary, is able to block enhancer-promoter interaction. Genes Dev 13 2098 2107

20. OhtsukiS

LevineM

1998 GAGA mediates the enhancer blocking activity of the eve promoter in the Drosophila embryo. Genes Dev 12 3325 3330

21. BelozerovVE

MajumderP

ShenP

CaiHN

2003 A novel boundary element may facilitate independent gene regulation in the Antennapedia complex of Drosophila. EMBO J 22 3113 3121

22. SchweinsbergS

HagstromK

GohlD

SchedlP

KumarRP

2004 The enhancer-blocking activity of the Fab-7 boundary from the Drosophila bithorax complex requires GAGA-factor-binding sites. Genetics 168 1371 1384

23. RosemanRR

PirrottaV

GeyerPK

1993 The su(Hw) protein insulates expression of the Drosophila melanogaster white gene from chromosomal position-effects. EMBO J 12 435 442

24. KahnTG

SchwartzYB

DellinoGI

PirrottaV

2006 Polycomb complexes and the propagation of the methylation mark at the Drosophila ubx gene. J Biol Chem 281 29064 29075

25. MallinDR

MyungJS

PattonJS

GeyerPK

1998 Polycomb group repression is blocked by the Drosophila suppressor of Hairy-wing [su(Hw)] insulator. Genetics 148 331 339

26. SigristCJ

PirrottaV

1997 Chromatin insulator elements block the silencing of a target gene by the Drosophila polycomb response element (PRE) but allow trans interactions between PREs on different chromosomes. Genetics 147 209 221

27. CuddapahS

JothiR

SchonesDE

RohTY

CuiK

2009 Global analysis of the insulator binding protein CTCF in chromatin barrier regions reveals demarcation of active and repressive domains. Genome Res 19 24 32

28. EmberlyE

BlattesR

SchuettengruberB

HennionM

JiangN

2008 BEAF regulates cell-cycle genes through the controlled deposition of H3K9 methylation marks into its conserved dual-core binding sites. PLoS Biol 6 e327 doi:10.1371/journal.pbio.0060327

29. JothiR

CuddapahS

BarskiA

CuiK

ZhaoK

2008 Genome-wide identification of in vivo protein-DNA binding sites from ChIP-Seq data. Nucleic Acids Res 36 5221 5231

30. BartkuhnM

StraubT

HeroldM

HerrmannM

RathkeC

2009 Active promoters and insulators are marked by the centrosomal protein 190. EMBO J

31. KimTH

AbdullaevZK

SmithAD

ChingKA

LoukinovDI

2007 Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome. Cell 128 1231 1245

32. SpanaC

HarrisonDA

CorcesVG

1988 The Drosophila melanogaster suppressor of Hairy-wing protein binds to specific sequences of the gypsy retrotransposon. Genes Dev 2 1414 1423

33. PollardD

2008 Bergman 2004 matrices.

34. HeintzmanND

HonGC

HawkinsRD

KheradpourP

StarkA

2009 Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature

35. BusheyAM

RamosE

CorcesVG

2009 Three subclasses of a Drosophila insulator show distinct and cell type-specific genomic distributions. Genes Dev 23 1338 1350

36. BernsteinBE

MikkelsenTS

XieX

KamalM

HuebertDJ

2006 A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell 125 315 326

37. MikkelsenTS

KuM

JaffeDB

IssacB

LiebermanE

2007 Genome-wide maps of chromatin state in pluripotent and lineage-committed cells. Nature 448 553 560

38. PanG

TianS

NieJ

YangC

RuottiV

2007 Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells. Cell Stem Cell 1 299 312

39. ZhaoXD

HanX

ChewJL

LiuJ

ChiuKP

2007 Whole-genome mapping of histone H3 Lys4 and 27 trimethylations reveals distinct genomic compartments in human embryonic stem cells. Cell Stem Cell 1 286 298

40. MacArthurS

LiXY

LiJ

BrownJB

ChuHC

2009 Developmental roles of 21 Drosophila transcription factors are determined by quantitative differences in binding to an overlapping set of thousands of genomic regions. Genome Biol 10 R80

41. CaoR

ZhangY

2004 The functions of E(Z)/EZH2-mediated methylation of lysine 27 in histone H3. Curr Opin Genet Dev 14 155 164

42. SchwartzYB

KahnTG

NixDA

LiXY

BourgonR

2006 Genome-wide analysis of Polycomb targets in Drosophila melanogaster. Nat Genet 38 700 705

43. SchuettengruberB

GanapathiM

LeblancB

PortosoM

JaschekR

2009 Functional anatomy of polycomb and trithorax chromatin landscapes in Drosophila embryos. PLoS Biol 7 e13 doi:10.1371/journal.pbio.1000013

44. TolhuisB

de WitE

MuijrersI

TeunissenH

TalhoutW

2006 Genome-wide profiling of PRC1 and PRC2 Polycomb chromatin binding in Drosophila melanogaster. Nat Genet 38 694 699

45. NegreN

HennetinJ

SunLV

LavrovS

BellisM

2006 Chromosomal distribution of PcG proteins during Drosophila development. PLoS Biol 4 e170 doi:10.1371/journal.pbio.0040170

46. HalliganDL

KeightleyPD

2006 Ubiquitous selective constraints in the Drosophila genome revealed by a genome-wide interspecies comparison. Genome Res 16 875 884

47. BhutkarA

SchaefferSW

RussoSM

XuM

SmithTF

2008 Chromosomal rearrangement inferred from comparisons of 12 Drosophila genomes. Genetics 179 1657 1680

48. EngstromPG

Ho SuiSJ

DrivenesO

BeckerTS

LenhardB

2007 Genomic regulatory blocks underlie extensive microsynteny conservation in insects. Genome Res 17 1898 1908

49. DionMF

KaplanT

KimM

BuratowskiS

FriedmanN

2007 Dynamics of replication-independent histone turnover in budding yeast. Science 315 1405 1408

50. MitoY

HenikoffJG

HenikoffS

2005 Genome-scale profiling of histone H3.3 replacement patterns. Nat Genet 37 1090 1097

51. HenikoffS

HenikoffJG

SakaiA

LoebGB

AhmadK

2009 Genome-wide profiling of salt fractions maps physical properties of chromatin. Genome Res 19 460 469

52. 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

53. JiangN

EmberlyE

CuvierO

HartCM

2009 Genome-wide mapping of boundary element-associated factor (BEAF) binding sites in Drosophila melanogaster links BEAF to transcription. Mol Cell Biol 29 3556 3568

54. BartkuhnM

StraubT

HeroldM

HerrmannM

RathkeC

2009 Active promoters and insulators are marked by the centrosomal protein 190. EMBO J 28 877 888

55. MaedaRK

KarchF

2003 Ensuring enhancer fidelity. Nat Genet 34 360 361

56. LeeCK

ShibataY

RaoB

StrahlBD

LiebJD

2004 Evidence for nucleosome depletion at active regulatory regions genome-wide. Nat Genet 36 900 905

57. GeyerPK

1997 The role of insulator elements in defining domains of gene expression. Curr Opin Genet Dev 7 242 248

58. ChopraVS

CandeJ

HongJW

LevineM

2009 Stalled Hox promoters as chromosomal boundaries. Genes Dev 23 1505 1509

59. NegreN

LavrovS

HennetinJ

BellisM

CavalliG

2006 Mapping the distribution of chromatin proteins by ChIP on chip. Methods Enzymol 410 316 341

60. WhitfieldWG

ChaplinMA

OegemaK

ParryH

GloverDM

1995 The 190 kDa centrosome-associated protein of Drosophila melanogaster contains four zinc finger motifs and binds to specific sites on polytene chromosomes. J Cell Sci 108 (Pt 11) 3377 3387

61. GerasimovaTI

CorcesVG

1998 Polycomb and trithorax group proteins mediate the function of a chromatin insulator. Cell 92 511 521

62. GerasimovaTI

GdulaDA

GerasimovDV

SimonovaO

CorcesVG

1995 A Drosophila protein that imparts directionality on a chromatin insulator is an enhancer of position-effect variegation. Cell 82 587 597

63. ParnellTJ

KuhnEJ

GilmoreBL

HelouC

WoldMS

2006 Identification of genomic sites that bind the Drosophila suppressor of Hairy-wing insulator protein. Mol Cell Biol 26 5983 5993

64. TsukiyamaT

WuC

1996 Purification of GAGA factor of Drosophila and its role in nucleosome disruption. Methods Enzymol 274 291 299

65. JohnsonWE

LiW

MeyerCA

GottardoR

CarrollJS

2006 Model-based analysis of tiling-arrays for ChIP-chip. Proc Natl Acad Sci U S A 103 12457 12462

66. BaileyTL

ElkanC

1994 Fitting a mixture model by expectation maximization to discover motifs in biopolymers. Proc Int Conf Intell Syst Mol Biol 2 28 36

67. HughesJD

EstepPW

TavazoieS

ChurchGM

2000 Computational identification of cis-regulatory elements associated with groups of functionally related genes in Saccharomyces cerevisiae. J Mol Biol 296 1205 1214

68. LiuXS

BrutlagDL

LiuJS

2002 An algorithm for finding protein-DNA binding sites with applications to chromatin-immunoprecipitation microarray experiments. Nat Biotechnol 20 835 839

69. KheradpourP

StarkA

RoyS

KellisM

2007 Reliable prediction of regulator targets using 12 Drosophila genomes. Genome Res 17 1919 1931

70. TouzetH

VarreJS

2007 Efficient and accurate P-value computation for Position Weight Matrices. Algorithms Mol Biol 2 15

71. HalfonMS

GalloSM

BergmanCM

2008 REDfly 2.0: an integrated database of cis-regulatory modules and transcription factor binding sites in Drosophila. Nucleic Acids Res 36 D594 598

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2010 Číslo 1
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#