#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Nucleolin Is Required for DNA Methylation State and the Expression of rRNA Gene Variants in


In eukaryotes, 45S rRNA genes are arranged in tandem arrays in copy numbers ranging from several hundred to several thousand in plants. Although it is clear that not all copies are transcribed under normal growth conditions, the molecular basis controlling the expression of specific sets of rRNA genes remains unclear. Here, we report four major rRNA gene variants in Arabidopsis thaliana. Interestingly, while transcription of one of these rRNA variants is induced, the others are either repressed or remain unaltered in A. thaliana plants with a disrupted nucleolin-like protein gene (Atnuc-L1). Remarkably, the most highly represented rRNA gene variant, which is inactive in WT plants, is reactivated in Atnuc-L1 mutants. We show that accumulated pre–rRNAs originate from RNA Pol I transcription and are processed accurately. Moreover, we show that disruption of the AtNUC-L1 gene induces loss of symmetrical DNA methylation without affecting histone epigenetic marks at rRNA genes. Collectively, these data reveal a novel mechanism for rRNA gene transcriptional regulation in which the nucleolin protein plays a major role in controlling active and repressed rRNA gene variants in Arabidopsis.


Vyšlo v časopise: Nucleolin Is Required for DNA Methylation State and the Expression of rRNA Gene Variants in. PLoS Genet 6(11): e32767. doi:10.1371/journal.pgen.1001225
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1001225

Souhrn

In eukaryotes, 45S rRNA genes are arranged in tandem arrays in copy numbers ranging from several hundred to several thousand in plants. Although it is clear that not all copies are transcribed under normal growth conditions, the molecular basis controlling the expression of specific sets of rRNA genes remains unclear. Here, we report four major rRNA gene variants in Arabidopsis thaliana. Interestingly, while transcription of one of these rRNA variants is induced, the others are either repressed or remain unaltered in A. thaliana plants with a disrupted nucleolin-like protein gene (Atnuc-L1). Remarkably, the most highly represented rRNA gene variant, which is inactive in WT plants, is reactivated in Atnuc-L1 mutants. We show that accumulated pre–rRNAs originate from RNA Pol I transcription and are processed accurately. Moreover, we show that disruption of the AtNUC-L1 gene induces loss of symmetrical DNA methylation without affecting histone epigenetic marks at rRNA genes. Collectively, these data reveal a novel mechanism for rRNA gene transcriptional regulation in which the nucleolin protein plays a major role in controlling active and repressed rRNA gene variants in Arabidopsis.


Zdroje

1. LamYW

Trinkle-MulcahyL

LamondAI

2005 The nucleolus. J Cell Sci 118 1335 1337

2. ShawP

DoonanJ

2005 The nucleolus. Playing by different rules? Cell Cycle 4 102 105. Epub 2005 Jan 2013

3. Saez-VasquezJ

MedinaFJ

2008 The plant nucleolus. Botanical Research: Incorporating Advances in Plant Pathology, Vol 47. San Diego Elsevier Academic Press Inc 1 46

4. GrummtI

2003 Life on a planet of its own: regulation of RNA polymerase I transcription in the nucleolus. Genes Dev 17 1691 1702

5. ReederRH

1992 Regulation of transcription by RNA polymerase I. Transcriptional Regulation: Cold Spring Harbor Laboratory Press

6. Saez-VasquezJ

EcheverriaM

2006 Polymerase I transcription.

GrasserKD

Regulation of transcription in plants Oxford, UK Blackwell 162 183

7. PikaardCS

ReederRH

1988 Sequence elements essential for function of the Xenopus laevis ribosomal DNA enhancers. Mol Cell Biol 8 4282 4288

8. PikaardCS

PapeLK

HendersonSL

RyanK

PaalmanMH

1990 Enhancers for RNA polymerase I in mouse ribosomal DNA. Mol Cell Biol 10 4816 4825

9. DoellingJH

GaudinoRJ

PikaardCS

1993 Functional analysis of Arabidopsis thaliana rRNA gene and spacer promoters in vivo and by transient expression. Proc Natl Acad Sci U S A 90 7528 7532

10. WanzenbockEM

SchoferC

SchweizerD

BachmairA

1997 Ribosomal transcription units integrated via T-DNA transformation associate with the nucleolus and do not require upstream repeat sequences for activity in Arabidopsis thaliana. Plant J 11 1007 1016

11. PreussS

PikaardCS

2007 rRNA gene silencing and nucleolar dominance: insights into a chromosome-scale epigenetic on/off switch. Biochim Biophys Acta 1769 383 392. Epub 2007 Mar 2012

12. ChenZJ

ComaiL

PikaardCS

1998 Gene dosage and stochastic effects determine the severity and direction of uniparental ribosomal RNA gene silencing (nucleolar dominance) in Arabidopsis allopolyploids. Proc Natl Acad Sci U S A 95 14891 14896

13. 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

14. ProbstAV

FagardM

ProuxF

MourrainP

BoutetS

2004 Arabidopsis histone deacetylase HDA6 is required for maintenance of transcriptional gene silencing and determines nuclear organization of rDNA repeats. Plant Cell 16 1021 1034. Epub 2004 Mar 1022

15. PreussSB

Costa-NunesP

TuckerS

PontesO

LawrenceRJ

2008 Multimegabase silencing in nucleolar dominance involves siRNA-directed DNA methylation and specific methylcytosine-binding proteins. Mol Cell 32 673 684

16. EarleyKW

PontvianneF

WierzbickiAT

BlevinsT

TuckerS

2010 Mechanisms of HDA6-mediated rRNA gene silencing: suppression of intergenic Pol II transcription and differential effects on maintenance versus siRNA-directed cytosine methylation. Genes Dev 24 1119 1132

17. BenderJ

2004 Chromatin-based silencing mechanisms. Curr Opin Plant Biol 7 521 526

18. PontvianneF

MatiaI

DouetJ

TourmenteS

MedinaFJ

2007 Characterization of AtNUC-L1 reveals a central role of nucleolin in nucleolus organization and silencing of AtNUC-L2 gene in Arabidopsis. Mol Biol Cell 18 369 379

19. GinistyH

SicardH

RogerB

BouvetP

1999 Structure and functions of nucleolin. J Cell Sci 112 761 772

20. RogerB

MoisandA

AmalricF

BouvetP

2002 Repression of RNA polymerase I transcription by nucleolin is independent of the RNA sequence that is transcribed. J Biol Chem 277 10209 10219. Epub 12001 Dec 10231

21. RogerB

MoisandA

AmalricF

BouvetP

2003 Nucleolin provides a link between RNA polymerase I transcription and pre-ribosome assembly. Chromosoma 111 399 407. Epub 2003 Feb 2011

22. YanagidaM

ShimamotoA

NishikawaK

FuruichiY

IsobeT

2001 Isolation and proteomic characterization of the major proteins of the nucleolin-binding ribonucleoprotein complexes. Proteomics 1 1390 1404

23. AngelovD

BondarenkoVA

AlmagroS

MenoniH

MongelardF

2006 Nucleolin is a histone chaperone with FACT-like activity and assists remodeling of nucleosomes. Embo J 25 1669 1679. Epub 2006 Apr 1666

24. UgrinovaI

MonierK

IvaldiC

ThiryM

StorckS

2007 Inactivation of nucleolin leads to nucleolar disruption, cell cycle arrest and defects in centrosome duplication. BMC Mol Biol 8 66

25. BogreL

JonakC

MinkM

MeskieneI

TraasJ

1996 Developmental and cell cycle regulation of alfalfa nucMs1, a plant homolog of the yeast Nsr1 and mammalian nucleolin. Plant Cell 8 417 428

26. DidierDK

KleeHJ

1992 Identification of an Arabidopsis DNA-binding protein with homology to nucleolin. Plant Mol Biol 18 977 979

27. KojimaH

SuzukiT

KatoT

EnomotoKI

SatoS

2007 Sugar-inducible expression of the nucleolin-1 gene of Arabidopsis thaliana and its role in ribosome synthesis, growth and development. Plant J 6 6

28. PetrickaJJ

NelsonTM

2007 Arabidopsis nucleolin affects plant development and patterning. Plant Physiol 144 173 186. Epub 2007 Mar 2016

29. PontesO

LawrenceRJ

SilvaM

PreussS

Costa-NunesP

2007 Postembryonic establishment of megabase-scale gene silencing in nucleolar dominance. PLoS ONE 2 e1157 doi:10.1371/journal.pone.0001157

30. ComellaP

PontvianneF

LahmyS

VignolsF

BarbezierN

2008 Characterization of a ribonuclease III-like protein required for cleavage of the pre-rRNA in the 3′ETS in Arabidopsis. Nucleic Acids Res 36 1163 1175

31. KufelJ

DichtlB

TollerveyD

1999 Yeast Rnt1p is required for cleavage of the pre-ribosomal RNA in the 3′ ETS but not the 5′ ETS. Rna 5 909 917

32. BarnecheF

SteinmetzF

EcheverriaM

2000 Fibrillarin genes encode both a conserved nucleolar protein and a novel small nucleolar RNA involved in ribosomal RNA methylation in Arabidopsis thaliana. J Biol Chem 275 27212 27220

33. FrenchSL

OsheimYN

CiociF

NomuraM

BeyerAL

2003 In exponentially growing Saccharomyces cerevisiae cells, rRNA synthesis is determined by the summed RNA polymerase I loading rate rather than by the number of active genes. Mol Cell Biol 23 1558 1568

34. SanijE

PoortingaG

SharkeyK

HungS

HollowayTP

2008 UBF levels determine the number of active ribosomal RNA genes in mammals. J Cell Biol 183 1259 1274

35. 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

36. CopenhaverGP

PikaardCS

1996 Two-dimensional RFLP analyses reveal megabase-sized clusters of rRNA gene variants in Arabidopsis thaliana, suggesting local spreading of variants as the mode for gene homogenization during concerted evolution. Plant J 9 273 282

37. LawrenceRJ

PikaardCS

2004 Chromatin turn ons and turn offs of ribosomal RNA genes. Cell Cycle 3 880 883. Epub 2004 Jul 2021

38. TariqM

PaszkowskiJ

2004 DNA and histone methylation in plants. Trends Genet 20 244 251

39. PontesO

LiCF

NunesPC

HaagJ

ReamT

2006 The Arabidopsis chromatin-modifying nuclear siRNA pathway involves a nucleolar RNA processing center. Cell 126 79 92

40. ChenZJ

PikaardCS

1997 Transcriptional analysis of nucleolar dominance in polyploid plants: biased expression/silencing of progenitor rRNA genes is developmentally regulated in Brassica. Proc Natl Acad Sci U S A 94 3442 3447

41. KomarovaNY

GrabeT

HuigenDJ

HemlebenV

VolkovRA

2004 Organization, differential expression and methylation of rDNA in artificial Solanum allopolyploids. Plant Mol Biol 56 439 463

42. MayerC

SchmitzKM

LiJ

GrummtI

SantoroR

2006 Intergenic transcripts regulate the epigenetic state of rRNA genes. Mol Cell 22 351 361

43. SantoroR

LiJ

GrummtI

2002 The nucleolar remodeling complex NoRC mediates heterochromatin formation and silencing of ribosomal gene transcription. Nat Genet 32 393 396. Epub 2002 Oct 2007

44. ErardMS

BelenguerP

Caizergues-FerrerM

PantaloniA

AmalricF

1988 A major nucleolar protein, nucleolin, induces chromatin decondensation by binding to histone H1. Eur J Biochem 175 525 530

45. KharratA

DerancourtJ

DoreeM

AmalricF

ErardM

1991 Synergistic effect of histone H1 and nucleolin on chromatin condensation in mitosis: role of a phosphorylated heteromer. Biochemistry 30 10329 10336

46. KermekchievM

WorkmanJL

PikaardCS

1997 Nucleosome binding by the polymerase I transactivator upstream binding factor displaces linker histone H1. Mol Cell Biol 17 5833 5842

47. StefanovskyV

LangloisF

Gagnon-KuglerT

RothblumLI

MossT

2006 Growth factor signaling regulates elongation of RNA polymerase I transcription in mammals via UBF phosphorylation and r-chromatin remodeling. Mol Cell 21 629 639

48. GerbiSA

BorovjaginAV

LangeTS

2003 The nucleolus: a site of ribonucleoprotein maturation. Curr Opin Cell Biol 15 318 325

49. PontesO

LawrenceRJ

NevesN

SilvaM

LeeJH

2003 Natural variation in nucleolar dominance reveals the relationship between nucleolus organizer chromatin topology and rRNA gene transcription in Arabidopsis. Proc Natl Acad Sci U S A 100 11418 11423. Epub 12003 Sep 11422

50. KakutaniT

MunakataK

RichardsEJ

HirochikaH

1999 Meiotically and mitotically stable inheritance of DNA hypomethylation induced by ddm1 mutation of Arabidopsis thaliana. Genetics 151 831 838

51. KankelMW

RamseyDE

StokesTL

FlowersSK

HaagJR

2003 Arabidopsis MET1 cytosine methyltransferase mutants. Genetics 163 1109 1122

52. VongsA

KakutaniT

MartienssenRA

RichardsEJ

1993 Arabidopsis thaliana DNA methylation mutants. Science 260 1926 1928

53. 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

54. Saez-VasquezJ

Caparros-RuizD

BarnecheF

EcheverriaM

2004 A plant snoRNP complex containing snoRNAs, fibrillarin, and nucleolin-like proteins is competent for both rRNA gene binding and pre-rRNA processing in vitro. Mol Cell Biol 24 7284 7297

55. SamahaH

DelormeV

PontvianneF

CookeR

DelalandeF

2009 Identification of protein factors and U3 snoRNAs from a Brassica oleracea RNP complex involved in the processing of pre-rRNA. Plant J

56. MongelardF

BouvetP

2007 Nucleolin: a multiFACeTed protein. Trends Cell Biol 17 80 86

57. ChodavarapuRK

FengS

BernatavichuteYV

ChenPY

StroudH

2010 Relationship between nucleosome positioning and DNA methylation. Nature

58. SegalE

WidomJ

2009 What controls nucleosome positions? Trends Genet 25 335 343

59. MathieuO

ReindersJ

CaikovskiM

SmathajittC

PaszkowskiJ

2007 Transgenerational stability of the Arabidopsis epigenome is coordinated by CG methylation. Cell 130 851 862

60. WooHR

DittmerTA

RichardsEJ

2008 Three SRA-domain methylcytosine-binding proteins cooperate to maintain global CpG methylation and epigenetic silencing in Arabidopsis. PLoS Genet 4 e1000156 doi:10.1371/journal.pgen.1000156

61. GruendlerP

UnfriedI

PointnerR

SchweizerD

1989 Nucleotide sequence of the 25S-18S ribosomal gene spacer from Arabidopsis thaliana. Nucleic Acids Res 17 6395 6396

62. WierzbickiAT

HaagJR

PikaardCS

2008 Noncoding transcription by RNA polymerase Pol IVb/Pol V mediates transcriptional silencing of overlapping and adjacent genes. Cell 135 635 648

63. 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

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2010 Číslo 11
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#