-
Články
- Časopisy
- Kurzy
- Témy
- Kongresy
- Videa
- Podcasty
DNA Topoisomerase 1α Promotes Transcriptional Silencing of Transposable Elements through DNA Methylation and Histone Lysine 9 Dimethylation in
DNA topoisomerase is an enzyme that releases the torsional stress in DNA generated during DNA replication or transcription. Here, we uncovered an unexpected role of DNA topoisomerase 1α (TOP1α) in the maintenance of genome stability. Eukaryotic genomes are usually littered with transposable elements (TEs) and repeats, which pose threats to genome stability due to their tendency to move or recombine. Mechanisms are in place to silence these elements, such as RNA-directed DNA methylation (RdDM) and histone H3 lysine 9 dimethylation (H3K9me2) in plants. Two plant-specific RNA polymerases, Pol IV and Pol V, generate small and long noncoding RNAs, respectively, from TEs and repeats. These RNAs then recruit protein factors to deposit DNA methylation or H3K9me2 to silence the loci. In this study, we found that treatment of plants with camptothecin, a TOP1α inhibitor, or loss of function in TOP1α, led to the de-repression of RdDM target loci, which was accompanied by loss of H3K9me2 or DNA methylation. The role of TOP1α in RdDM could be attributed to its promotion of Pol V, but not Pol IV, transcription to generate long noncoding RNAs.
Vyšlo v časopise: DNA Topoisomerase 1α Promotes Transcriptional Silencing of Transposable Elements through DNA Methylation and Histone Lysine 9 Dimethylation in. PLoS Genet 10(7): e32767. doi:10.1371/journal.pgen.1004446
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004446Souhrn
DNA topoisomerase is an enzyme that releases the torsional stress in DNA generated during DNA replication or transcription. Here, we uncovered an unexpected role of DNA topoisomerase 1α (TOP1α) in the maintenance of genome stability. Eukaryotic genomes are usually littered with transposable elements (TEs) and repeats, which pose threats to genome stability due to their tendency to move or recombine. Mechanisms are in place to silence these elements, such as RNA-directed DNA methylation (RdDM) and histone H3 lysine 9 dimethylation (H3K9me2) in plants. Two plant-specific RNA polymerases, Pol IV and Pol V, generate small and long noncoding RNAs, respectively, from TEs and repeats. These RNAs then recruit protein factors to deposit DNA methylation or H3K9me2 to silence the loci. In this study, we found that treatment of plants with camptothecin, a TOP1α inhibitor, or loss of function in TOP1α, led to the de-repression of RdDM target loci, which was accompanied by loss of H3K9me2 or DNA methylation. The role of TOP1α in RdDM could be attributed to its promotion of Pol V, but not Pol IV, transcription to generate long noncoding RNAs.
Zdroje
1. BirdA (2007) Perceptions of epigenetics. Nature 447 : 396–398.
2. LawJA, JacobsenSE (2010) Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nature Rev Genet 11 : 204–220.
3. HerrAJ, JensenMB, DalmayT, BaulcombeDC (2005) RNA polymerase IV directs silencing of endogenous DNA. Science 308 : 118–120.
4. KannoT, HuettelB, MetteMF, AufsatzW, JaligotE, et al. (2005) Atypical RNA polymerase subunits required for RNA-directed DNA methylation. Nature Genetics 37 : 761–765.
5. OnoderaY, HaagJR, ReamT, Costa NunesP, PontesO, et al. (2005) Plant nuclear RNA polymerase IV mediates siRNA and DNA methylation-dependent heterochromatin formation. Cell 120 : 613–622.
6. PontierD, YahubyanG, VegaD, BulskiA, Saez-VasquezJ, et al. (2005) Reinforcement of silencing at transposons and highly repeated sequences requires the concerted action of two distinct RNA polymerases IV in Arabidopsis. Genes & Development 19 : 2030–2040.
7. ZilbermanD, CaoX, JacobsenSE (2003) ARGONAUTE4 control of locus-specific siRNA accumulation and DNA and histone methylation. Science 299 : 716–719.
8. 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.
9. WierzbickiAT, ReamTS, HaagJR, PikaardCS (2009) RNA polymerase V transcription guides ARGONAUTE4 to chromatin. Nature Genetics 41 : 630–634.
10. ZemachA, KimMY, HsiehPH, Coleman-DerrD, Eshed-WilliamsL, et al. (2013) The Arabidopsis nucleosome remodeler DDM1 allows DNA methyltransferases to access H1-containing heterochromatin. Cell 153 : 193–205.
11. EbbsML, BarteeL, BenderJ (2005) H3 lysine 9 methylation is maintained on a transcribed inverted repeat by combined action of SUVH6 and SUVH4 methyltransferases. Molecular and cellular biology 25 : 10507–10515.
12. EbbsML, BenderJ (2006) Locus-specific control of DNA methylation by the Arabidopsis SUVH5 histone methyltransferase. The Plant cell 18 : 1166–1176.
13. JacksonJP, LindrothAM, CaoX, JacobsenSE (2002) Control of CpNpG DNA methylation by the KRYPTONITE histone H3 methyltransferase. Nature 416 : 556–560.
14. DuJ, ZhongX, BernatavichuteYV, StroudH, FengS, et al. (2012) Dual binding of chromomethylase domains to H3K9me2-containing nucleosomes directs DNA methylation in plants. Cell 151 : 167–180.
15. EnkeRA, DongZ, BenderJ (2011) Small RNAs prevent transcription-coupled loss of histone H3 lysine 9 methylation in Arabidopsis thaliana. PLoS genetics 7: e1002350.
16. StroudH, DoT, DuJ, ZhongX, FengS, et al. (2014) Non-CG methylation patterns shape the epigenetic landscape in Arabidopsis. Nature structural & molecular biology 21 : 64–72.
17. ChampouxJJ (2001) DNA topoisomerases: structure, function, and mechanism. Annual Review of Biochemistry 70 : 369–413.
18. VosSM, TretterEM, SchmidtBH, BergerJM (2011) All tangled up: how cells direct, manage and exploit topoisomerase function. Nature Rev Mol Cell Biol 12 : 827–841.
19. TakahashiT, MatsuharaS, AbeM, KomedaY (2002) Disruption of a DNA topoisomerase I gene affects morphogenesis in Arabidopsis. The Plant Cell 14 : 2085–2093.
20. DinhTT, O'LearyM, WonSY, LiS, ArroyoL, et al. (2013) Generation of a luciferase-based reporter for CHH and CG DNA methylation in Arabidopsis thaliana. Silence 4 : 1.
21. JaxelC, CapranicoG, KerriganD, KohnKW, PommierY (1991) Effect of local DNA sequence on topoisomerase I cleavage in the presence or absence of camptothecin. J Biol Chem 266 : 20418–20423.
22. StakerBL, HjerrildK, FeeseMD, BehnkeCA, BurginABJr, et al. (2002) The mechanism of topoisomerase I poisoning by a camptothecin analog. PNAS 99 : 15387–15392.
23. ManavellaPA, HagmannJ, OttF, LaubingerS, FranzM, et al. (2012) Fast-forward genetics identifies plant CPL phosphatases as regulators of miRNA processing factor HYL1. Cell 151 : 859–870.
24. IrizarryRA, Ladd-AcostaC, CarvalhoB, WuH, BrandenburgSA, et al. (2008) Comprehensive high-throughput arrays for relative methylation (CHARM). Genome Res 18 : 780–790.
25. LiQY, ZuYG, ShiRZ, YaoLP (2006) Review camptothecin: current perspectives. Current Medicinal Chemistry 13 : 2021–2039.
26. GrafP, DolzblaszA, WurschumT, LenhardM, PfreundtU, et al. (2010) MGOUN1 encodes an Arabidopsis type IB DNA topoisomerase required in stem cell regulation and to maintain developmentally regulated gene silencing. The Plant cell 22 : 716–728.
27. StroudH, GreenbergMV, FengS, BernatavichuteYV, JacobsenSE (2013) Comprehensive analysis of silencing mutants reveals complex regulation of the Arabidopsis methylome. Cell 152 : 352–364.
28. BeckerC, HagmannJ, MullerJ, KoenigD, StegleO, et al. (2011) Spontaneous epigenetic variation in the Arabidopsis thaliana methylome. Nature 480 : 245–249.
29. SchmitzRJ, SchultzMD, LewseyMG, O'MalleyRC, UrichMA, et al. (2011) Transgenerational epigenetic instability is a source of novel methylation variants. Science 334 : 369–373.
30. WierzbickiAT, CocklinR, MayampurathA, ListerR, RowleyMJ, et al. (2012) Spatial and functional relationships among Pol V-associated loci, Pol IV-dependent siRNAs, and cytosine methylation in the Arabidopsis epigenome. Genes & development 26 : 1825–1836.
31. 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.
32. LippmanZ, GendrelAV, BlackM, VaughnMW, DedhiaN, et al. (2004) Role of transposable elements in heterochromatin and epigenetic control. Nature 430 : 471–476.
33. TranRK, ZilbermanD, de BustosC, DittRF, HenikoffJG, et al. (2005) Chromatin and siRNA pathways cooperate to maintain DNA methylation of small transposable elements in Arabidopsis. Genome Biology 6: R90.
34. ZhengB, WangZ, LiS, YuB, LiuJY, et al. (2009) Intergenic transcription by RNA polymerase II coordinates Pol IV and Pol V in siRNA-directed transcriptional gene silencing in Arabidopsis. Genes & Development 23 : 2850–2860.
35. LiCF, PontesO, El-ShamiM, HendersonIR, BernatavichuteYV, et al. (2006) An ARGONAUTE4-containing nuclear processing center colocalized with Cajal bodies in Arabidopsis thaliana. Cell 126 : 93–106.
36. WonSY, LiS, ZhengB, ZhaoY, LiD, et al. (2012) Development of a luciferase-based reporter of transcriptional gene silencing that enables bidirectional mutant screening in Arabidopsis thaliana. Silence 3 : 6.
37. LiuLF, WangJC (1987) Supercoiling of the DNA template during transcription. PNAS 84 : 7024–7027.
38. Durand-DubiefM, PerssonJ, NormanU, HartsuikerE, EkwallK (2010) Topoisomerase I regulates open chromatin and controls gene expression in vivo. EMBO J 29 : 2126–2134.
39. Durand-DubiefM, SvenssonJP, PerssonJ, EkwallK (2011) Topoisomerases, chromatin and transcription termination. Transcription 2 : 66–70.
40. PikaardCS, HaagJR, PontesOM, BlevinsT, CocklinR (2013) A transcription fork model for Pol IV and Pol V-dependent RNA-directed DNA methylation. Cold Spring Harbor Symposia on Quantitative Biology 77 : 205–212.
41. MaeshimaK, LaemmliUK (2003) A two-step scaffolding model for mitotic chromosome assembly. Developmental Cell 4 : 467–480.
42. TadesseS, MascarenhasJ, KostersB, HasilikA, GraumannPL (2005) Genetic interaction of the SMC complex with topoisomerase IV in Bacillus subtilis. Microbiology 151 : 3729–3737.
43. KannoT, BucherE, DaxingerL, HuettelB, BohmdorferG, et al. (2008) A structural-maintenance-of-chromosomes hinge domain-containing protein is required for RNA-directed DNA methylation. Nature Genetics 40 : 670–675.
44. HuangHS, AllenJA, MabbAM, KingIF, MiriyalaJ, et al. (2012) Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature 481 : 185–189.
45. ChenPY, CokusSJ, PellegriniM (2010) BS Seeker: precise mapping for bisulfite sequencing. BMC Bioinformatics 11 : 203.
Štítky
Genetika Reprodukčná medicína
Článek Comparative Phylogenomics Uncovers the Impact of Symbiotic Associations on Host Genome EvolutionČlánek Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder PopulationČlánek Common Transcriptional Mechanisms for Visual Photoreceptor Cell Differentiation among PancrustaceansČlánek Integrative Genomics Reveals Novel Molecular Pathways and Gene Networks for Coronary Artery DiseaseČlánek An ARID Domain-Containing Protein within Nuclear Bodies Is Required for Sperm Cell Formation inČlánek Knock-In Reporter Mice Demonstrate that DNA Repair by Non-homologous End Joining Declines with Age
Článok vyšiel v časopisePLOS Genetics
Najčítanejšie tento týždeň
2014 Číslo 7- Gynekologové a odborníci na reprodukční medicínu se sejdou na prvním virtuálním summitu
- Je „freeze-all“ pro všechny? Odborníci na fertilitu diskutovali na virtuálním summitu
-
Všetky články tohto čísla
- Cuba: Exploring the History of Admixture and the Genetic Basis of Pigmentation Using Autosomal and Uniparental Markers
- Clonal Architecture of Secondary Acute Myeloid Leukemia Defined by Single-Cell Sequencing
- Mechanisms of Functional Variants That Impair Regulated Bicarbonate Permeation and Increase Risk for Pancreatitis but Not for Cystic Fibrosis
- Nucleosomes Shape DNA Polymorphism and Divergence
- Functional Diversification of Hsp40: Distinct J-Protein Functional Requirements for Two Prions Allow for Chaperone-Dependent Prion Selection
- Comparative Phylogenomics Uncovers the Impact of Symbiotic Associations on Host Genome Evolution
- Activation of the Immune System by Combinations of Common Alleles
- Age-Associated Sperm DNA Methylation Alterations: Possible Implications in Offspring Disease Susceptibility
- Muscle-Specific SIRT1 Gain-of-Function Increases Slow-Twitch Fibers and Ameliorates Pathophysiology in a Mouse Model of Duchenne Muscular Dystrophy
- MDRL lncRNA Regulates the Processing of miR-484 Primary Transcript by Targeting miR-361
- Hypersensitivity of Primordial Germ Cells to Compromised Replication-Associated DNA Repair Involves ATM-p53-p21 Signaling
- Intrapopulation Genome Size Variation in Reflects Life History Variation and Plasticity
- SlmA Antagonism of FtsZ Assembly Employs a Two-pronged Mechanism like MinCD
- Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population
- Determinative Developmental Cell Lineages Are Robust to Cell Deaths
- DELLA Protein Degradation Is Controlled by a Type-One Protein Phosphatase, TOPP4
- Wnt Signaling Interacts with Bmp and Edn1 to Regulate Dorsal-Ventral Patterning and Growth of the Craniofacial Skeleton
- Common Transcriptional Mechanisms for Visual Photoreceptor Cell Differentiation among Pancrustaceans
- UVB Induces a Genome-Wide Acting Negative Regulatory Mechanism That Operates at the Level of Transcription Initiation in Human Cells
- The Nesprin Family Member ANC-1 Regulates Synapse Formation and Axon Termination by Functioning in a Pathway with RPM-1 and β-Catenin
- Combinatorial Interactions Are Required for the Efficient Recruitment of Pho Repressive Complex (PhoRC) to Polycomb Response Elements
- Recombination in the Human Pseudoautosomal Region PAR1
- Microsatellite Interruptions Stabilize Primate Genomes and Exist as Population-Specific Single Nucleotide Polymorphisms within Individual Human Genomes
- An Intronic microRNA Links Rb/E2F and EGFR Signaling
- An Essential Nonredundant Role for Mycobacterial DnaK in Native Protein Folding
- Integrative Genomics Reveals Novel Molecular Pathways and Gene Networks for Coronary Artery Disease
- The Genomic Landscape of the Ewing Sarcoma Family of Tumors Reveals Recurrent Mutation
- Evolution and Genetic Architecture of Chromatin Accessibility and Function in Yeast
- An ARID Domain-Containing Protein within Nuclear Bodies Is Required for Sperm Cell Formation in
- Stage-Dependent and Locus-Specific Role of Histone Demethylase Jumonji D3 (JMJD3) in the Embryonic Stages of Lung Development
- Genome Wide Association Identifies Common Variants at the Locus Influencing Plasma Cortisol and Corticosteroid Binding Globulin
- Regulation of Feto-Maternal Barrier by Matriptase- and PAR-2-Mediated Signaling Is Required for Placental Morphogenesis and Mouse Embryonic Survival
- Apomictic and Sexual Germline Development Differ with Respect to Cell Cycle, Transcriptional, Hormonal and Epigenetic Regulation
- Functional EF-Hands in Neuronal Calcium Sensor GCAP2 Determine Its Phosphorylation State and Subcellular Distribution , and Are Essential for Photoreceptor Cell Integrity
- Comparison of Methods to Account for Relatedness in Genome-Wide Association Studies with Family-Based Data
- Knock-In Reporter Mice Demonstrate that DNA Repair by Non-homologous End Joining Declines with Age
- Cis and Trans Effects of Human Genomic Variants on Gene Expression
- 8.2% of the Human Genome Is Constrained: Variation in Rates of Turnover across Functional Element Classes in the Human Lineage
- Novel Approach Identifies SNPs in and with Evidence for Parent-of-Origin Effect on Body Mass Index
- Hypoxia Adaptations in the Grey Wolf () from Qinghai-Tibet Plateau
- A Loss of Function Screen of Identified Genome-Wide Association Study Loci Reveals New Genes Controlling Hematopoiesis
- Unraveling Genetic Modifiers in the Mouse Model of Absence Epilepsy
- DNA Topoisomerase 1α Promotes Transcriptional Silencing of Transposable Elements through DNA Methylation and Histone Lysine 9 Dimethylation in
- The Coding and Noncoding Architecture of the Genome
- A Novel Locus Is Associated with Large Artery Atherosclerotic Stroke Using a Genome-Wide Age-at-Onset Informed Approach
- Brg1 Loss Attenuates Aberrant Wnt-Signalling and Prevents Wnt-Dependent Tumourigenesis in the Murine Small Intestine
- The PTK7-Related Transmembrane Proteins Off-track and Off-track 2 Are Co-receptors for Wnt2 Required for Male Fertility
- The Co-factor of LIM Domains (CLIM/LDB/NLI) Maintains Basal Mammary Epithelial Stem Cells and Promotes Breast Tumorigenesis
- Essential Genetic Interactors of Required for Spatial Sequestration and Asymmetrical Inheritance of Protein Aggregates
- Meiosis-Specific Cohesin Component, Is Essential for Maintaining Centromere Chromatid Cohesion, and Required for DNA Repair and Synapsis between Homologous Chromosomes
- Silencing Is Noisy: Population and Cell Level Noise in Telomere-Adjacent Genes Is Dependent on Telomere Position and Sir2
- The Two Cis-Acting Sites, and , Contribute to the Longitudinal Organisation of Chromosome I
- A Broadly Conserved G-Protein-Coupled Receptor Kinase Phosphorylation Mechanism Controls Smoothened Activity
- Requirements for Acute Burn and Chronic Surgical Wound Infection
- LIN-42, the PERIOD homolog, Negatively Regulates MicroRNA Transcription
- WAPL Is Essential for the Prophase Removal of Cohesin during Meiosis
- Expression in Planarian Neoblasts after Injury Controls Anterior Pole Regeneration
- Sox11 Is Required to Maintain Proper Levels of Hedgehog Signaling during Vertebrate Ocular Morphogenesis
- Accumulation of a Threonine Biosynthetic Intermediate Attenuates General Amino Acid Control by Accelerating Degradation of Gcn4 via Pho85 and Cdk8
- PLOS Genetics
- Archív čísel
- Aktuálne číslo
- Informácie o časopise
Najčítanejšie v tomto čísle- Wnt Signaling Interacts with Bmp and Edn1 to Regulate Dorsal-Ventral Patterning and Growth of the Craniofacial Skeleton
- Novel Approach Identifies SNPs in and with Evidence for Parent-of-Origin Effect on Body Mass Index
- Hypoxia Adaptations in the Grey Wolf () from Qinghai-Tibet Plateau
- DNA Topoisomerase 1α Promotes Transcriptional Silencing of Transposable Elements through DNA Methylation and Histone Lysine 9 Dimethylation in
Prihlásenie#ADS_BOTTOM_SCRIPTS#Zabudnuté hesloZadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
- Časopisy