#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Nucleolar Association and Transcriptional Inhibition through 5S rDNA in Mammals


Changes in the spatial positioning of genes within the mammalian nucleus have been associated with transcriptional differences and thus have been hypothesized as a mode of regulation. In particular, the localization of genes to the nuclear and nucleolar peripheries is associated with transcriptional repression. However, the mechanistic basis, including the pertinent cis- elements, for such associations remains largely unknown. Here, we provide evidence that demonstrates a 119 bp 5S rDNA can influence nucleolar association in mammals. We found that integration of transgenes with 5S rDNA significantly increases the association of the host region with the nucleolus, and their degree of association correlates strongly with repression of a linked reporter gene. We further show that this mechanism may be functional in endogenous contexts: pseudogenes derived from 5S rDNA show biased conservation of their internal transcription factor binding sites and, in some cases, are frequently associated with the nucleolus. These results demonstrate that 5S rDNA sequence can significantly contribute to the positioning of a locus and suggest a novel, endogenous mechanism for nuclear organization in mammals.


Vyšlo v časopise: Nucleolar Association and Transcriptional Inhibition through 5S rDNA in Mammals. PLoS Genet 8(1): e32767. doi:10.1371/journal.pgen.1002468
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002468

Souhrn

Changes in the spatial positioning of genes within the mammalian nucleus have been associated with transcriptional differences and thus have been hypothesized as a mode of regulation. In particular, the localization of genes to the nuclear and nucleolar peripheries is associated with transcriptional repression. However, the mechanistic basis, including the pertinent cis- elements, for such associations remains largely unknown. Here, we provide evidence that demonstrates a 119 bp 5S rDNA can influence nucleolar association in mammals. We found that integration of transgenes with 5S rDNA significantly increases the association of the host region with the nucleolus, and their degree of association correlates strongly with repression of a linked reporter gene. We further show that this mechanism may be functional in endogenous contexts: pseudogenes derived from 5S rDNA show biased conservation of their internal transcription factor binding sites and, in some cases, are frequently associated with the nucleolus. These results demonstrate that 5S rDNA sequence can significantly contribute to the positioning of a locus and suggest a novel, endogenous mechanism for nuclear organization in mammals.


Zdroje

1. MisteliT 2007 Beyond the Sequence: Cellular Organization of Genome Function. Cell 128 787 800

2. TakizawaTMeaburnKJMisteliT 2008 The meaning of gene positioning. Cell 135 9 13

3. HakimiMABocharDASchmiesingJADongYBarakOG 2002 A chromatin remodelling complex that loads cohesin onto human chromosomes. Nature 418 994 998

4. AllenTAVon KaenelSGoodrichJAKugelJF 2004 The SINE-encoded mouse B2 RNA represses mRNA transcription in response to heat shock. Nat Struct Mol Biol 11 816 821

5. LunyakVVPrefontaineGGNunezECramerTJuBG 2007 Developmentally regulated activation of a SINE B2 repeat as a domain boundary in organogenesis. Science 317 248 251

6. PalmerAADulawaSC 2010 Murine Warriors or Worriers: The Saga of Comt1, B2 SINE Elements, and the Future of Translational Genetics. Front Neurosci 4 177

7. ThompsonMHaeuslerRAGoodPDEngelkeDR 2003 Nucleolar clustering of dispersed tRNA genes. Science 302 1399 1401

8. NomaKCamHPMaraiaRJGrewalSI 2006 A role for TFIIIC transcription factor complex in genome organization. Cell 125 859 872

9. WangLHaeuslerRAGoodPDThompsonMNagarS 2005 Silencing near tRNA genes requires nucleolar localization. J Biol Chem 280 8637 8639

10. SextonTUmlaufDKurukutiSFraserP 2007 The role of transcription factories in large-scale structure and dynamics of interphase chromatin. Semin Cell Dev Biol 18 691 697

11. PomboAJacksonDAHollinsheadMWangZRoederRG 1999 Regional specialization in human nuclei: visualization of discrete sites of transcription by RNA polymerase III. Embo J 18 2241 2253

12. KlausAVMcCarreyJRFarkasAWardWS 2001 Changes in DNA loop domain structure during spermatogenesis and embryogenesis in the Syrian golden hamster. Biol Reprod 64 1297 1306

13. HairAVassetzkyY 2007 Determination of the chromatin domain structure in arrayed repeat regions: organization of the somatic 5S RNA domain during embryogenesis in Xenopus laevis. J Cell Biochem 102 1140 1148

14. HaeuslerRAEngelkeDR 2006 Spatial organization of transcription by RNA polymerase III. Nucleic Acids Research 34 4826 4836

15. NemethAConesaASantoyo-LopezJMedinaIMontanerD 2010 Initial genomics of the human nucleolus. PLoS Genet 6 e1000889 doi:10.1371/journal.pgen.1000889

16. van KoningsbruggenSGierlinskiMSchofieldPMartinDBartonGJ 2010 High-resolution whole-genome sequencing reveals that specific chromatin domains from most human chromosomes associate with nucleoli. Mol Biol Cell 21 3735 3748

17. MaNMatsunagaSTakataHOno-ManiwaRUchiyamaS 2007 Nucleolin functions in nucleolus formation and chromosome congression. J Cell Sci 120 2091 2105

18. SantosFPetersAHOtteAPReikWDeanW 2005 Dynamic chromatin modifications characterise the first cell cycle in mouse embryos. Dev Biol 280 225 236

19. ProbstAVSantosFReikWAlmouzniGDeanW 2007 Structural differences in centromeric heterochromatin are spatially reconciled on fertilisation in the mouse zygote. Chromosoma 116 403 415

20. WongLHBrettingham-MooreKHChanLQuachJMAndersonMA 2007 Centromere RNA is a key component for the assembly of nucleoproteins at the nucleolus and centromere. Genome Res 17 1146 1160

21. ZhangLFHuynhKDLeeJT 2007 Perinucleolar targeting of the inactive X during S phase: evidence for a role in the maintenance of silencing. Cell 129 693 706

22. PandeyRRMondalTMohammadFEnrothSRedrupL 2008 Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell 32 232 246

23. MohammadFPandeyRRNaganoTChakalovaLMondalT 2008 Kcnq1ot1/Lit1 noncoding RNA mediates transcriptional silencing by targeting to the perinucleolar region. Mol Cell Biol 28 3713 3728

24. EllisNGoodfellowPN 1989 The mammalian pseudoautosomal region. Trends Genet 5 406 410

25. GuelenLPagieLBrassetEMeulemanWFazaMB 2008 Domain organization of human chromosomes revealed by mapping of nuclear lamina interactions. Nature 453 948 951

26. FinlanLESproulDThomsonIBoyleSKerrE 2008 Recruitment to the nuclear periphery can alter expression of genes in human cells. PLoS Genet 4 e1000039 doi:10.1371/journal.pgen.1000039

27. ReddyKLZulloJMBertolinoESinghH 2008 Transcriptional repression mediated by repositioning of genes to the nuclear lamina. Nature 452 243 247

28. KaiserTEIntineRVDundrM 2008 De novo formation of a subnuclear body. Science 322 1713 1717

29. OhlssonRLobanenkovVKlenovaE 2010 Does CTCF mediate between nuclear organization and gene expression? Bioessays 32 37 50

30. YusufzaiTMTagamiHNakataniYFelsenfeldG 2004 CTCF tethers an insulator to subnuclear sites, suggesting shared insulator mechanisms across species. Mol Cell 13 291 298

31. MoqtaderiZWangJRahaDWhiteRJSnyderM 2010 Genomic binding profiles of functionally distinct RNA polymerase III transcription complexes in human cells. Nat Struct Mol Biol 17 635 640

32. OlerAJAllaRKRobertsDNWongAHollenhorstPC 2010 Human RNA polymerase III transcriptomes and relationships to Pol II promoter chromatin and enhancer-binding factors. Nat Struct Mol Biol 17 620 628

33. Dumay-OdelotHDurrieu-GaillardSDa SilvaDRoederRGTeichmannM 2010 Cell growth- and differentiation-dependent regulation of RNA polymerase III transcription. Cell Cycle 9 3687 3699

34. PillaiMMVenkataramanGMKosakSTorok-StorbB 2008 Integration site analysis in transgenic mice by thermal asummetric interlaced (TAIL)-PCR: segregating multiple integrant founder lines and determining zygosity. Transgenic Research 17 749 754

35. BultmanSJGebuhrTCMagnusonT 2005 A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in beta-globin expression and erythroid development. Genes Dev 19 2849 2861

36. ZukerM 2003 Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Research 31 3406 3415

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2012 Číslo 1
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz
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#