#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

DNA Methyltransferases Are Required to Induce Heterochromatic Re-Replication in Arabidopsis


The relationship between epigenetic marks on chromatin and the regulation of DNA replication is poorly understood. Mutations of the H3K27 methyltransferase genes, ARABIDOPSIS TRITHORAX-RELATED PROTEIN5 (ATXR5) and ATXR6, result in re-replication (repeated origin firing within the same cell cycle). Here we show that mutations that reduce DNA methylation act to suppress the re-replication phenotype of atxr5 atxr6 mutants. This suggests that DNA methylation, a mark enriched at the same heterochromatic regions that re-replicate in atxr5/6 mutants, is required for aberrant re-replication. In contrast, RNA sequencing analyses suggest that ATXR5/6 and DNA methylation cooperatively transcriptionally silence transposable elements (TEs). Hence our results suggest a complex relationship between ATXR5/6 and DNA methylation in the regulation of DNA replication and transcription of TEs.


Vyšlo v časopise: DNA Methyltransferases Are Required to Induce Heterochromatic Re-Replication in Arabidopsis. PLoS Genet 8(7): e32767. doi:10.1371/journal.pgen.1002808
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002808

Souhrn

The relationship between epigenetic marks on chromatin and the regulation of DNA replication is poorly understood. Mutations of the H3K27 methyltransferase genes, ARABIDOPSIS TRITHORAX-RELATED PROTEIN5 (ATXR5) and ATXR6, result in re-replication (repeated origin firing within the same cell cycle). Here we show that mutations that reduce DNA methylation act to suppress the re-replication phenotype of atxr5 atxr6 mutants. This suggests that DNA methylation, a mark enriched at the same heterochromatic regions that re-replicate in atxr5/6 mutants, is required for aberrant re-replication. In contrast, RNA sequencing analyses suggest that ATXR5/6 and DNA methylation cooperatively transcriptionally silence transposable elements (TEs). Hence our results suggest a complex relationship between ATXR5/6 and DNA methylation in the regulation of DNA replication and transcription of TEs.


Zdroje

1. GreenBMFinnKJLiJJ 2010 Loss of DNA replication control is a potent inducer of gene amplification. Science 329 943 946

2. AriasEEWalterJC 2007 Strength in numbers: preventing rereplication via multiple mechanisms in eukaryotic cells. Genes Dev 21 497 518

3. LeeTJPascuzziPESettlageSBShultzRWTanurdzicM 2010 Arabidopsis thaliana chromosome 4 replicates in two phases that correlate with chromatin state. PLoS Genet 6 e1000982 doi:10.1371/journal.pgen.1000982

4. WhiteEJEmanuelssonOScalzoDRoyceTKosakS 2004 DNA replication-timing analysis of human chromosome 22 at high resolution and different developmental states. Proc Natl Acad Sci U S A 101 17771 17776

5. BirneyEStamatoyannopoulosJADuttaAGuigoRGingerasTR 2007 Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447 799 816

6. LawJAJacobsenSE 2010 Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet 11 204 220

7. JacobYStroudHLeblancCFengSZhuoL 2010 Regulation of heterochromatic DNA replication by histone H3 lysine 27 methyltransferases. Nature 466 987 991

8. BernatavichuteYVZhangXCokusSPellegriniMJacobsenSE 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

9. JacobYFengSLeBlancCABernatavichuteYVStroudH 2009 ATXR5 and ATXR6 are H3K27 monomethyltransferases required for chromatin structure and gene silencing. Nat Struct Mol Biol 16 763 768

10. MathieuOProbstAVPaszkowskiJ 2005 Distinct regulation of histone H3 methylation at lysines 27 and 9 by CpG methylation in Arabidopsis. Embo J 24 2783 2791

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

12. InagakiSMiura-KamioANakamuraYLuFCuiX 2010 Autocatalytic differentiation of epigenetic modifications within the Arabidopsis genome. Embo J 29 3496 3506

13. AmedeoPHabuYAfsarKMittelsten ScheidOPaszkowskiJ 2000 Disruption of the plant gene MOM releases transcriptional silencing of methylated genes. Nature 405 203 206

14. EbbsMLBenderJ 2006 Locus-specific control of DNA methylation by the Arabidopsis SUVH5 histone methyltransferase. Plant Cell 18 1166 1176

15. Ramirez-ParraEGutierrezC 2007 E2F regulates FASCIATA1, a chromatin assembly gene whose loss switches on the endocycle and activates gene expression by changing the epigenetic status. Plant Physiol 144 105 120

16. LangmeadBTrapnellCPopMSalzbergSL 2009 Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 10 R25

17. MortazaviAWilliamsBAMcCueKSchaefferLWoldB 2008 Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5 621 628

18. BenjaminiYHochbergY 1995 Controlling the False Discovery Rate: a Practical and Powerful Approach to Multiple Testing. Journal of the Royal Statistical Society Series B 57 12

19. ChenPYCokusSJPellegriniM 2010 BS Seeker: precise mapping for bisulfite sequencing. BMC Bioinformatics 11 203

20. ZhangXYazakiJSundaresanACokusSChanSW 2006 Genome-wide high-resolution mapping and functional analysis of DNA methylation in arabidopsis. Cell 126 1189 1201

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2012 Číslo 7
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#