#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Convergent Transcription Induces Dynamic DNA Methylation at Loci


Cytosine methylation of DNA is an important epigenetic gene silencing mechanism in plants, fungi, and animals. In the filamentous fungus Neurospora crassa, nearly all known DNA methylations occur in transposon relics and repetitive sequences, and DNA methylation does not depend on the canonical RNAi pathway. disiRNAs are Dicer-independent small non-coding RNAs that arise from gene-rich part of the Neurospora genome. Here we describe a new type of DNA methylation that is associated with the disiRNA loci. Unlike the known DNA methylation in Neurospora, disiRNA loci DNA methylation (DLDM) is highly dynamic and is regulated by an on/off mechanism. Some disiRNA production appears to rely on pol II directed transcription. Importantly, DLDM is triggered by convergent transcription and enriched in promoter regions. Together, our results establish a new mechanism that triggers DNA methylation.


Vyšlo v časopise: Convergent Transcription Induces Dynamic DNA Methylation at Loci. PLoS Genet 9(9): e32767. doi:10.1371/journal.pgen.1003761
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003761

Souhrn

Cytosine methylation of DNA is an important epigenetic gene silencing mechanism in plants, fungi, and animals. In the filamentous fungus Neurospora crassa, nearly all known DNA methylations occur in transposon relics and repetitive sequences, and DNA methylation does not depend on the canonical RNAi pathway. disiRNAs are Dicer-independent small non-coding RNAs that arise from gene-rich part of the Neurospora genome. Here we describe a new type of DNA methylation that is associated with the disiRNA loci. Unlike the known DNA methylation in Neurospora, disiRNA loci DNA methylation (DLDM) is highly dynamic and is regulated by an on/off mechanism. Some disiRNA production appears to rely on pol II directed transcription. Importantly, DLDM is triggered by convergent transcription and enriched in promoter regions. Together, our results establish a new mechanism that triggers DNA methylation.


Zdroje

1. FreitagM, SelkerEU (2005) Controlling DNA methylation: many roads to one modification. Curr Opin Genet Dev 15: 191–199.

2. SuzukiMM, BirdA (2008) DNA methylation landscapes: provocative insights from epigenomics. Nat Rev Genet 9: 465–476.

3. WuSC, ZhangY (2010) Active DNA demethylation: many roads lead to Rome. Nat Rev Mol Cell Biol 11: 607–620.

4. VolpeTA, KidnerC, HallIM, TengG, GrewalSI, et al. (2002) Regulation of heterochromatic silencing and histone H3 lysine-9 methylation by RNAi. Science 297: 1833–1837.

5. BuhlerM, MoazedD (2007) Transcription and RNAi in heterochromatic gene silencing. Nat Struct Mol Biol 14: 1041–1048.

6. VerdelA, JiaS, GerberS, SugiyamaT, GygiS, et al. (2004) RNAi-mediated targeting of heterochromatin by the RITS complex. Science 303: 672–676.

7. HeXJ, ChenT, ZhuJK (2011) Regulation and function of DNA methylation in plants and animals. Cell Res 21: 442–465.

8. HaagJR, PikaardCS (2011) Multisubunit RNA polymerases IV and V: purveyors of non-coding RNA for plant gene silencing. Nat Rev Mol Cell Biol 12: 483–492.

9. AravinAA, SachidanandamR, Bourc'hisD, SchaeferC, PezicD, et al. (2008) A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell 31: 785–799.

10. Kuramochi-MiyagawaS, WatanabeT, GotohK, TotokiY, ToyodaA, et al. (2008) DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev 22: 908–917.

11. SelkerEU, FritzDY, SingerMJ (1993) Dense nonsymmetrical DNA methylation resulting from repeat-induced point mutation in Neurospora. Science 262: 1724–1728.

12. LewisZA, HondaS, KhlafallahTK, JeffressJK, FreitagM, et al. (2009) Relics of repeat-induced point mutation direct heterochromatin formation in Neurospora crassa. Genome Res 19: 427–437.

13. RountreeMR, SelkerEU (2010) DNA methylation and the formation of heterochromatin in Neurospora crassa. Heredity (Edinb) 105: 38–44.

14. CambareriEB, JensenBC, SchabtachE, SelkerEU (1989) Repeat-induced G-C to A-T mutations in Neurospora. Science 244: 1571–1575.

15. TamaruH, ZhangX, McMillenD, SinghPB, NakayamaJ, et al. (2003) Trimethylated lysine 9 of histone H3 is a mark for DNA methylation in Neurospora crassa. Nat Genet 34: 75–79.

16. TamaruH, SelkerEU (2001) A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414: 277–283.

17. KouzminovaE, SelkerEU (2001) dim-2 encodes a DNA methyltransferase responsible for all known cytosine methylation in Neurospora. EMBO J 20: 4309–4323.

18. FreitagM, HickeyPC, KhlafallahTK, ReadND, SelkerEU (2004) HP1 is essential for DNA methylation in neurospora. Mol Cell 13: 427–434.

19. HondaS, SelkerEU (2008) Direct interaction between DNA methyltransferase DIM-2 and HP1 is required for DNA methylation in Neurospora crassa. Molecular and cellular biology 28: 6044–6055.

20. FreitagM, LeeDW, KotheGO, PrattRJ, AramayoR, et al. (2004) DNA methylation is independent of RNA interference in Neurospora. Science 304: 1939.

21. DangY, YangQ, XueZ, LiuY (2011) RNA interference in fungi: pathways, functions, and applications. Eukaryot Cell 10: 1148–1155.

22. LeeHC, LiL, GuW, XueZ, CrosthwaiteSK, et al. (2010) Diverse Pathways Generate MicroRNA-like RNAs and Dicer-Independent Small Interfering RNAs in Fungi. Mol Cell 38: 803–814.

23. ZhaoY, ShenY, YangS, WangJ, HuQ, et al. (2010) Ubiquitin ligase components Cullin4 and DDB1 are essential for DNA methylation in Neurospora crassa. J Biol Chem 285: 4355–4365.

24. SelkerEU, StevensJN (1985) DNA methylation at asymmetric sites is associated with numerous transition mutations. Proc Natl Acad Sci U S A 82: 8114–8118.

25. MargolinBS, Garrett-EngelePW, StevensJN, FritzDY, Garrett-EngeleC, et al. (1998) A methylated Neurospora 5S rRNA pseudogene contains a transposable element inactivated by repeat-induced point mutation. Genetics 149: 1787–1797.

26. SingerMJ, MarcotteBA, SelkerEU (1995) DNA methylation associated with repeat-induced point mutation in Neurospora crassa. Mol Cell Biol 15: 5586–5597.

27. HondaS, SelkerEU (2008) Direct interaction between DNA methyltransferase DIM-2 and HP1 is required for DNA methylation in Neurospora crassa. Mol Cell Biol 28: 6044–6055.

28. KramerC, LorosJJ, DunlapJC, CrosthwaiteSK (2003) Role for antisense RNA in regulating circadian clock function in Neurospora crassa. Nature 421: 948–952.

29. HeintzenC, LiuY (2007) The Neurospora crassa circadian clock. Adv Genet 58: 25–66.

30. YangQ, LiL, XueZ, YeQ, ZhangL, et al. (2013) Transcription of the major neurospora crassa microRNA-like small RNAs relies on RNA polymerase III. PLoS Genet 9: e1003227.

31. MaitiM, LeeHC, LiuY (2007) QIP, a putative exonuclease, interacts with the Neurospora Argonaute protein and facilitates conversion of duplex siRNA into single strands. Genes Dev 21: 590–600.

32. SelkerEU, TountasNA, CrossSH, MargolinBS, MurphyJG, et al. (2003) The methylated component of the Neurospora crassa genome. Nature 422: 893–897.

33. SelkerEU (1990) Premeiotic instability of repeated sequences in Neurospora crassa. Annual review of genetics 24: 579–613.

34. FiczG, BrancoMR, SeisenbergerS, SantosF, KruegerF, et al. (2011) Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 473: 398–402.

35. BeldenWJ, LewisZA, SelkerEU, LorosJJ, DunlapJC (2011) CHD1 remodels chromatin and influences transient DNA methylation at the clock gene frequency. PLoS Genet 7: e1002166.

36. O'SullivanJM, Tan-WongSM, MorillonA, LeeB, ColesJ, et al. (2004) Gene loops juxtapose promoters and terminators in yeast. Nature genetics 36: 1014–1018.

37. AnsariA, HampseyM (2005) A role for the CPF 3′-end processing machinery in RNAP II-dependent gene looping. Genes & development 19: 2969–2978.

38. Tan-WongSM, ZauggJB, CamblongJ, XuZ, ZhangDW, et al. (2012) Gene loops enhance transcriptional directionality. Science 338: 671–675.

39. ChoudharyS, LeeHC, MaitiM, HeQ, ChengP, et al. (2007) A double-stranded-RNA response program important for RNA interference efficiency. Mol Cell Biol 27: 3995–4005.

40. HeQ, ChengP, YangY, WangL, GardnerKH, et al. (2002) White collar-1, a DNA binding transcription factor and a light sensor. Science 297: 840–843.

41. DavisRL, deSerresD (1970) Genetic and microbial research techniques for Neurospora crassa. Methods of Enzymology 27A: 79–143.

42. ChengP, YangY, LiuY (2001) Interlocked feedback loops contribute to the robustness of the Neurospora circadian clock. Proc Natl Acad Sci U S A 98: 7408–7413.

43. PomraningKR, SmithKM, FreitagM (2009) Genome-wide high throughput analysis of DNA methylation in eukaryotes. Methods 47: 142–150.

44. WeberM, DaviesJJ, WittigD, OakeleyEJ, HaaseM, et al. (2005) Chromosome-wide and promoter-specific analyses identify sites of differential DNA methylation in normal and transformed human cells. Nat Genet 37: 853–862.

45. GuoJ, ChengP, YuanH, LiuY (2009) The exosome regulates circadian gene expression in a posttranscriptional negative feedback loop. Cell 138: 1236–1246.

46. MarquesJT, KimK, WuPH, AlleyneTM, JafariN, et al. (2010) Loqs and R2D2 act sequentially in the siRNA pathway in Drosophila. Nat Struct Mol Biol 17: 24–30.

47. GitA, DvingeH, Salmon-DivonM, OsborneM, KutterC, et al. (2010) Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression. RNA 16: 991–1006.

48. ZhangL, ChiaJM, KumariS, SteinJC, LiuZ, et al. (2009) A genome-wide characterization of microRNA genes in maize. PLoS Genet 5: e1000716.

49. SteinLD, MungallC, ShuS, CaudyM, MangoneM, et al. (2002) The generic genome browser: a building block for a model organism system database. Genome Res 12: 1599–1610.

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2013 Číslo 9
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#