#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

siRNA–Mediated Methylation of Telomeres


Chromosome termini form a specialized type of heterochromatin that is important for chromosome stability. The recent discovery of telomeric RNA transcripts in yeast and vertebrates raised the question of whether RNA–based mechanisms are involved in the formation of telomeric heterochromatin. In this study, we performed detailed analysis of chromatin structure and RNA transcription at chromosome termini in Arabidopsis. Arabidopsis telomeres display features of intermediate heterochromatin that does not extensively spread to subtelomeric regions which encode transcriptionally active genes. We also found telomeric repeat–containing transcripts arising from telomeres and centromeric loci, a portion of which are processed into small interfering RNAs. These telomeric siRNAs contribute to the maintenance of telomeric chromatin through promoting methylation of asymmetric cytosines in telomeric (CCCTAAA)n repeats. The formation of telomeric siRNAs and methylation of telomeres relies on the RNA–dependent DNA methylation pathway. The loss of telomeric DNA methylation in rdr2 mutants is accompanied by only a modest effect on histone heterochromatic marks, indicating that maintenance of telomeric heterochromatin in Arabidopsis is reinforced by several independent mechanisms. In conclusion, this study provides evidence for an siRNA–directed mechanism of chromatin maintenance at telomeres in Arabidopsis.


Vyšlo v časopise: siRNA–Mediated Methylation of Telomeres. PLoS Genet 6(6): e32767. doi:10.1371/journal.pgen.1000986
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1000986

Souhrn

Chromosome termini form a specialized type of heterochromatin that is important for chromosome stability. The recent discovery of telomeric RNA transcripts in yeast and vertebrates raised the question of whether RNA–based mechanisms are involved in the formation of telomeric heterochromatin. In this study, we performed detailed analysis of chromatin structure and RNA transcription at chromosome termini in Arabidopsis. Arabidopsis telomeres display features of intermediate heterochromatin that does not extensively spread to subtelomeric regions which encode transcriptionally active genes. We also found telomeric repeat–containing transcripts arising from telomeres and centromeric loci, a portion of which are processed into small interfering RNAs. These telomeric siRNAs contribute to the maintenance of telomeric chromatin through promoting methylation of asymmetric cytosines in telomeric (CCCTAAA)n repeats. The formation of telomeric siRNAs and methylation of telomeres relies on the RNA–dependent DNA methylation pathway. The loss of telomeric DNA methylation in rdr2 mutants is accompanied by only a modest effect on histone heterochromatic marks, indicating that maintenance of telomeric heterochromatin in Arabidopsis is reinforced by several independent mechanisms. In conclusion, this study provides evidence for an siRNA–directed mechanism of chromatin maintenance at telomeres in Arabidopsis.


Zdroje

1. BlascoMA

2007 The epigenetic regulation of mammalian telomeres. Nat Rev Genet 8 299 309

2. OttavianiA

GilsonE

MagdinierF

2008 Telomeric position effect: from the yeast paradigm to human pathologies? Biochimie 90 93 107

3. MichishitaE

McCordRA

BerberE

KioiM

Padilla-NashH

2008 SIRT6 is a histone H3 lysine 9 deacetylase that modulates telomeric chromatin. Nature 452 492 496

4. Garcia-CaoM

O'SullivanR

PetersAH

JenuweinT

BlascoMA

2004 Epigenetic regulation of telomere length in mammalian cells by the Suv39h1 and Suv39h2 histone methyltransferases. Nat Genet 36 94 99

5. GonzaloS

Garcia-CaoM

FragaMF

SchottaG

PetersAH

2005 Role of the RB1 family in stabilizing histone methylation at constitutive heterochromatin. Nat Cell Biol 7 420 428

6. JonesB

SuH

BhatA

LeiH

BajkoJ

2008 The histone H3K79 methyltransferase Dot1L is essential for mammalian development and heterochromatin structure. PLoS Genet 4 e1000190 doi:10.1371/journal.pgen.1000190

7. GonzaloS

JacoI

FragaMF

ChenT

LiE

2006 DNA methyltransferases control telomere length and telomere recombination in mammalian cells. Nat Cell Biol 8 416 424

8. ZaratieguiM

IrvineDV

MartienssenRA

2007 Noncoding RNAs and gene silencing. Cell 128 763 776

9. LukeB

PanzaA

RedonS

IglesiasN

LiZ

2008 The Rat1p 5′ to 3′ exonuclease degrades telomeric repeat-containing RNA and promotes telomere elongation in Saccharomyces cerevisiae. Mol Cell 32 465 477

10. AzzalinCM

ReichenbachP

KhoriauliL

GiulottoE

LingnerJ

2007 Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318 798 801

11. SchoeftnerS

BlascoMA

2008 Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat Cell Biol 10 228 236

12. YehezkelS

SegevY

Viegas-PequignotE

SkoreckiK

SeligS

2008 Hypomethylation of subtelomeric regions in ICF syndrome is associated with abnormally short telomeres and enhanced transcription from telomeric regions. Hum Mol Genet 17 2776 2789

13. DengZ

NorseenJ

WiedmerA

RiethmanH

LiebermanPM

2009 TERRA RNA binding to TRF2 facilitates heterochromatin formation and ORC recruitment at telomeres. Mol Cell 35 403 413

14. MoazedD

2009 Small RNAs in transcriptional gene silencing and genome defence. Nature 457 413 420

15. PikaardCS

HaagJR

ReamT

WierzbickiAT

2008 Roles of RNA polymerase IV in gene silencing. Trends Plant Sci 13 390 397

16. MatzkeM

KannoT

DaxingerL

HuettelB

MatzkeAJ

2009 RNA-mediated chromatin-based silencing in plants. Curr Opin Cell Biol

17. 2000 Analysis of the genome sequence of the flowering plant Arabidopsis thaliana. Nature 408 796 815

18. HeacockM

SpanglerE

RihaK

PuizinaJ

ShippenDE

2004 Molecular analysis of telomere fusions in Arabidopsis: multiple pathways for chromosome end-joining. Embo J 23 2304 2313

19. CopenhaverGP

PikaardCS

1996 RFLP and physical mapping with an rDNA-specific endonuclease reveals that nucleolus organizer regions of Arabidopsis thaliana adjoin the telomeres on chromosomes 2 and 4. Plant J 9 259 272

20. KuoHF

OlsenKM

RichardsEJ

2006 Natural variation in a subtelomeric region of Arabidopsis: implications for the genomic dynamics of a chromosome end. Genetics 173 401 417

21. BernatavichuteYV

ZhangX

CokusS

PellegriniM

JacobsenSE

2008 Genome-wide association of histone H3 lysine nine methylation with CHG DNA methylation in Arabidopsis thaliana. PLoS ONE 3 e3156 doi:10.1371/journal.pone.0003156

22. HabuY

MathieuO

TariqM

ProbstAV

SmathajittC

2006 Epigenetic regulation of transcription in intermediate heterochromatin. EMBO Rep 7 1279 1284

23. MayBP

LippmanZB

FangY

SpectorDL

MartienssenRA

2005 Differential regulation of strand-specific transcripts from Arabidopsis centromeric satellite repeats. PLoS Genet 1 e79 doi:10.1371/journal.pgen.0010079

24. HuettelB

KannoT

DaxingerL

BucherE

van der WindenJ

2007 RNA-directed DNA methylation mediated by DRD1 and Pol IVb: a versatile pathway for transcriptional gene silencing in plants. Biochim Biophys Acta 1769 358 374

25. MosherRA

SchwachF

StudholmeD

BaulcombeDC

2008 PolIVb influences RNA-directed DNA methylation independently of its role in siRNA biogenesis. Proc Natl Acad Sci U S A 105 3145 3150

26. ZhangX

HendersonIR

LuC

GreenPJ

JacobsenSE

2007 Role of RNA polymerase IV in plant small RNA metabolism. Proc Natl Acad Sci U S A 104 4536 4541

27. HeXJ

HsuYF

ZhuS

WierzbickiAT

PontesO

2009 An effector of RNA-directed DNA methylation in arabidopsis is an ARGONAUTE 4- and RNA-binding protein. Cell 137 498 508

28. WierzbickiAT

ReamTS

HaagJR

PikaardCS

2009 RNA polymerase V transcription guides ARGONAUTE4 to chromatin. Nat Genet 41 630 634

29. MiS

CaiT

HuY

ChenY

HodgesE

2008 Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5′ terminal nucleotide. Cell 133 116 127

30. CokusSJ

FengS

ZhangX

ChenZ

MerrimanB

2008 Shotgun bisulphite sequencing of the Arabidopsis genome reveals DNA methylation patterning. Nature 452 215 219

31. PerrodS

GasserSM

2003 Long-range silencing and position effects at telomeres and centromeres: parallels and differences. Cell Mol Life Sci 60 2303 2318

32. PrydeFE

GorhamHC

LouisEJ

1997 Chromosome ends: all the same under their caps. Curr Opin Genet Dev 7 822 828

33. TommerupH

DousmanisA

de LangeT

1994 Unusual chromatin in human telomeres. Mol Cell Biol 14 5777 5785

34. FajkusJ

KovarikA

KralovicsR

BezdekM

1995 Organization of telomeric and subtelomeric chromatin in the higher plant Nicotiana tabacum. Mol Gen Genet 247 633 638

35. SykorovaE

FajkusJ

ItoM

FukuiK

2001 Transition between two forms of heterochromatin at plant subtelomeres. Chromosome Res 9 309 323

36. LippmanZ

MayB

YordanC

SingerT

MartienssenR

2003 Distinct mechanisms determine transposon inheritance and methylation via small interfering RNA and histone modification. PLoS Biol 1 e67 doi:10.1371/journal.pbio.0000067

37. BenettiR

SchoeftnerS

MunozP

BlascoMA

2008 Role of TRF2 in the assembly of telomeric chromatin. Cell Cycle 7 3461 3468

38. HorardB

GilsonE

2008 Telomeric RNA enters the game. Nat Cell Biol 10 113 115

39. LukeB

LingnerJ

2009 TERRA: telomeric repeat-containing RNA. Embo J 28 2503 2510

40. TremousaygueD

ManevskiA

BardetC

LescureN

LescureB

1999 Plant interstitial telomere motifs participate in the control of gene expression in root meristems. Plant J 20 553 561

41. ZellingerB

RihaK

2007 Composition of plant telomeres. Biochim Biophys Acta 1769 399 409

42. DaxingerL

KannoT

BucherE

van der WindenJ

NaumannU

2009 A stepwise pathway for biogenesis of 24-nt secondary siRNAs and spreading of DNA methylation. Embo J 28 48 57

43. DejardinJ

KingstonRE

2009 Purification of proteins associated with specific genomic Loci. Cell 136 175 186

44. ListerR

PelizzolaM

DowenRH

HawkinsRD

HonG

2009 Human DNA methylomes at base resolution show widespread epigenomic differences. Nature

45. GrafiG

Ben-MeirH

AviviY

MosheM

DahanY

2007 Histone methylation controls telomerase-independent telomere lengthening in cells undergoing dedifferentiation. Dev Biol 306 838 846

46. KanohJ

SadaieM

UranoT

IshikawaF

2005 Telomere binding protein Taz1 establishes Swi6 heterochromatin independently of RNAi at telomeres. Curr Biol 15 1808 1819

47. HoCY

MurnaneJP

YeungAK

NgHK

LoAW

2008 Telomeres acquire distinct heterochromatin characteristics during siRNA-induced RNA interference in mouse cells. Curr Biol 18 183 187

48. CaoF

LiX

HiewS

BradyH

LiuY

2009 Dicer independent small RNAs associate with telomeric heterochromatin. Rna 15 1274 1281

49. RihaK

FajkusJ

SirokyJ

VyskotB

1998 Developmental control of telomere lengths and telomerase activity in plants. Plant Cell 10 1691 1698

50. HetzlJ

FoersterAM

RaidlG

Mittelsten ScheidO

2007 CyMATE: a new tool for methylation analysis of plant genomic DNA after bisulphite sequencing. Plant J 51 526 536

51. LawrenceRJ

EarleyK

PontesO

SilvaM

ChenZJ

2004 A concerted DNA methylation/histone methylation switch regulates rRNA gene dosage control and nucleolar dominance. Mol Cell 13 599 609

52. LiR

LiYR

KristiansenK

WangJ

2008 SOAP: short oligonucleotide aligment program. Bioinformatics 24 713

53. AkimchevaS

ZellingerB

RihaK

2008 Genome stability in Arabidopsis cells exhibiting alternative lengthening of telomeres. Cytogenet Genome Res 122 388 395

54. RihaK

McKnightTD

GriffingLR

ShippenDE

2001 Living with genome instability: plant responses to telomere dysfunction. Science 291 1797 1800

55. FitzgeraldMS

RihaK

GaoF

RenS

McKnightTD

1999 Disruption of the telomerase catalytic subunit gene from Arabidopsis inactivates telomerase and leads to a slow loss of telomeric DNA. Proc Natl Acad Sci U S A 96 14813 14818

56. ZellingerB

AkimchevaS

PuizinaJ

SchiratoM

RihaK

2007 Ku suppresses formation of telomeric circles and alternative telomere lengthening in Arabidopsis. Mol Cell 27 163 169

57. RihaK

WatsonJM

ParkeyJ

ShippenDE

2002 Telomere length deregulation and enhanced sensitivity to genotoxic stress in Arabidopsis mutants deficient in Ku70. Embo J 21 2819 2826

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2010 Číslo 6
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Aktuální možnosti diagnostiky a léčby litiáz
nový kurz
Autori: MUDr. Tomáš Ürge, PhD.

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#