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1

Wendte, Jered M., Jeremy R. Haag, Olga M. Pontes, Jasleen Singh, Sara Metcalf, and Craig S. Pikaard. "The Pol IV largest subunit CTD quantitatively affects siRNA levels guiding RNA-directed DNA methylation." Nucleic Acids Research 47, no. 17 (2019): 9024–36. http://dx.doi.org/10.1093/nar/gkz615.

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Abstract In plants, nuclear multisubunit RNA polymerases IV and V are RNA Polymerase II-related enzymes that synthesize non-coding RNAs for RNA-directed DNA methylation (RdDM) and transcriptional gene silencing. Here, we tested the importance of the C-terminal domain (CTD) of Pol IV’s largest subunit given that the Pol II CTD mediates multiple aspects of Pol II transcription. We show that the CTD is dispensable for Pol IV catalytic activity and Pol IV termination-dependent activation of RNA-DEPENDENT RNA POLYMERASE 2, which partners with Pol IV to generate dsRNA precursors of the 24 nt siRNAs
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2

Zhong, Xuehua, Christopher J. Hale, Minh Nguyen, et al. "DOMAINS REARRANGED METHYLTRANSFERASE3 controls DNA methylation and regulates RNA polymerase V transcript abundance in Arabidopsis." Proceedings of the National Academy of Sciences 112, no. 3 (2015): 911–16. http://dx.doi.org/10.1073/pnas.1423603112.

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DNA methylation is a mechanism of epigenetic gene regulation and genome defense conserved in many eukaryotic organisms. In Arabidopsis, the DNA methyltransferase DOMAINS REARRANGED METHYLASE 2 (DRM2) controls RNA-directed DNA methylation in a pathway that also involves the plant-specific RNA Polymerase V (Pol V). Additionally, the Arabidopsis genome encodes an evolutionarily conserved but catalytically inactive DNA methyltransferase, DRM3. Here, we show that DRM3 has moderate effects on global DNA methylation and small RNA abundance and that DRM3 physically interacts with Pol V. In Arabidopsis
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3

Taochy, Christelle, Agnès Yu, Nicolas Bouché, et al. "Post-transcriptional gene silencing triggers dispensable DNA methylation in gene body in Arabidopsis." Nucleic Acids Research 47, no. 17 (2019): 9104–14. http://dx.doi.org/10.1093/nar/gkz636.

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Abstract Spontaneous post-transcriptional silencing of sense transgenes (S-PTGS) is established in each generation and is accompanied by DNA methylation, but the pathway of PTGS-dependent DNA methylation is unknown and so is its role. Here we show that CHH and CHG methylation coincides spatially and temporally with RDR6-dependent products derived from the central and 3′ regions of the coding sequence, and requires the components of the RNA-directed DNA methylation (RdDM) pathway NRPE1, DRD1 and DRM2, but not CLSY1, NRPD1, RDR2 or DCL3, suggesting that RDR6-dependent products, namely long dsRNA
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4

Rao, Xiaolan, Shengli Yang, Shiyou Lü, and Pingfang Yang. "DNA Methylation Dynamics in Response to Drought Stress in Crops." Plants 13, no. 14 (2024): 1977. http://dx.doi.org/10.3390/plants13141977.

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Drought is one of the most hazardous environmental factors due to its severe damage on plant growth, development and productivity. Plants have evolved complex regulatory networks and resistance strategies for adaptation to drought stress. As a conserved epigenetic regulation, DNA methylation dynamically alters gene expression and chromosome interactions in plants’ response to abiotic stresses. The development of omics technologies on genomics, epigenomics and transcriptomics has led to a rapid increase in research on epigenetic variation in non-model crop species. In this review, we summarize
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5

Lewsey, Mathew G., Thomas J. Hardcastle, Charles W. Melnyk, et al. "Mobile small RNAs regulate genome-wide DNA methylation." Proceedings of the National Academy of Sciences 113, no. 6 (2016): E801—E810. http://dx.doi.org/10.1073/pnas.1515072113.

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RNA silencing at the transcriptional and posttranscriptional levels regulates endogenous gene expression, controls invading transposable elements (TEs), and protects the cell against viruses. Key components of the mechanism are small RNAs (sRNAs) of 21–24 nt that guide the silencing machinery to their nucleic acid targets in a nucleotide sequence-specific manner. Transcriptional gene silencing is associated with 24-nt sRNAs and RNA-directed DNA methylation (RdDM) at cytosine residues in three DNA sequence contexts (CG, CHG, and CHH). We previously demonstrated that 24-nt sRNAs are mobile from
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6

Wang, Lili, Kezhi Zheng, Longjun Zeng, et al. "Reinforcement of CHH methylation through RNA-directed DNA methylation ensures sexual reproduction in rice." Plant Physiology 188, no. 2 (2021): 1189–209. http://dx.doi.org/10.1093/plphys/kiab531.

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Abstract DNA methylation is an important epigenetic mark that regulates the expression of genes and transposons. RNA-directed DNA methylation (RdDM) is the main molecular pathway responsible for de novo DNA methylation in plants. Although the mechanism of RdDM has been well studied in Arabidopsis (Arabidopsis thaliana), most mutations in RdDM genes cause no remarkable developmental defects in Arabidopsis. Here, we isolated and cloned Five Elements Mountain 1 (FEM1), which encodes RNA-dependent RNA polymerase 2 (OsRDR2) in rice (Oryza sativa). Mutation in OsRDR2 abolished the accumulation of 24
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7

Zheng, Kezhi, Lili Wang, Longjun Zeng, et al. "The effect of RNA polymerase V on 24-nt siRNA accumulation depends on DNA methylation contexts and histone modifications in rice." Proceedings of the National Academy of Sciences 118, no. 30 (2021): e2100709118. http://dx.doi.org/10.1073/pnas.2100709118.

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RNA-directed DNA methylation (RdDM) functions in de novo methylation in CG, CHG, and CHH contexts. Here, we performed map-based cloning of OsNRPE1, which encodes the largest subunit of RNA polymerase V (Pol V), a key regulator of gene silencing and reproductive development in rice. We found that rice Pol V is required for CHH methylation on RdDM loci by transcribing long noncoding RNAs. Pol V influences the accumulation of 24-nucleotide small interfering RNAs (24-nt siRNAs) in a locus-specific manner. Biosynthesis of 24-nt siRNAs on loci with high CHH methylation levels and low CG and CHG meth
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8

Baev, Vesselin, Mladen Naydenov, Elena Apostolova, et al. "Identification of RNA-dependent DNA-methylation regulated promoters in Arabidopsis." Plant Physiology and Biochemistry 48, no. 6 (2010): 393–400. http://dx.doi.org/10.1016/j.plaphy.2010.03.013.

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9

Wang, Lili, Dachao Xu, Longjun Zeng, and Donglei Yang. "The Rise and Fall of Billionaire siRNAs during Reproductive Development in Rice." Plants 11, no. 15 (2022): 1957. http://dx.doi.org/10.3390/plants11151957.

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RNA polymerase IV-dependent siRNAs, usually 24 nt in length, function in the RNA-directed DNA methylation that is responsible for de novo methylation in plants. We analyzed 24 nt siRNAs in inflorescences and found that among the 20,200 24 nt siRNA clusters, the top 0.81% highly expressed clusters accounted for more than 68% of the 24 nt siRNA reads in inflorescences. We named the highly expressed siRNAs as billionaire siRNAs (bill-siRNAs) and the less-expressed siRNAs as pauper siRNAs (pau-siRNAs). The bill-siRNAs in inflorescences are mainly derived from the ovary. Female gametes produced mor
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10

Weng, JingRong, JinXin Lin, YuMo Xie, et al. "Abstract 6006: RNA m6A methylation relay the oncogenic flow from DNA methylationto gene expression of ANKRD13B." Cancer Research 83, no. 7_Supplement (2023): 6006. http://dx.doi.org/10.1158/1538-7445.am2023-6006.

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Abstract Background: Colorectal cancer (CRC) is one of the most common causes of cancer-related death in the world. More comprehensive studies of key molecular alterations in CRC progression were urgent. DNA methylation promotes tumor progression. However, the mechanism of the ANKRD13 gene methylation that drives colorectal cancer evolution remains largely unknown. This was the first study focused on the role of ANKRD13 and the hypermethylated mechanisms in colorectal cancer. Methods: Chi-Square tests were utilized to the comparison of the baseline characteristics of patients with hypomethylat
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11

Guo, Wei, Dafang Wang, and Damon Lisch. "RNA-directed DNA methylation prevents rapid and heritable reversal of transposon silencing under heat stress in Zea mays." PLOS Genetics 17, no. 6 (2021): e1009326. http://dx.doi.org/10.1371/journal.pgen.1009326.

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In large complex plant genomes, RNA-directed DNA methylation (RdDM) ensures that epigenetic silencing is maintained at the boundary between genes and flanking transposable elements. In maize, RdDM is dependent on Mediator of Paramutation 1 (Mop1), a putative RNA dependent RNA polymerase. Here we show that although RdDM is essential for the maintenance of DNA methylation of a silenced MuDR transposon in maize, a loss of that methylation does not result in a restoration of activity. Instead, heritable maintenance of silencing is maintained by histone modifications. At one terminal inverted repea
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12

Goll, Mary Grace, Finn Kirpekar, Keith A. Maggert, et al. "Methylation of tRNAAsp by the DNA Methyltransferase Homolog Dnmt2." Science 311, no. 5759 (2006): 395–98. http://dx.doi.org/10.1126/science.1120976.

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The sequence and the structure of DNA methyltransferase-2 (Dnmt2) bear close affinities to authentic DNA cytosine methyltransferases. A combined genetic and biochemical approach revealed that human DNMT2 did not methylate DNA but instead methylated a small RNA; mass spectrometry showed that this RNA is aspartic acid transfer RNA (tRNAAsp) and that DNMT2 specifically methylated cytosine 38 in the anticodon loop. The function of DNMT2 is highly conserved, and human DNMT2 protein restored methylation in vitro to tRNAAsp from Dnmt2-deficient strains of mouse, Arabidopsis thaliana, and Drosophila m
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13

Sigman, Meredith J., Kaushik Panda, Rachel Kirchner, et al. "An siRNA-guided ARGONAUTE protein directs RNA polymerase V to initiate DNA methylation." Nature Plants 7, no. 11 (2021): 1461–74. http://dx.doi.org/10.1038/s41477-021-01008-7.

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AbstractIn mammals and plants, cytosine DNA methylation is essential for the epigenetic repression of transposable elements and foreign DNA. In plants, DNA methylation is guided by small interfering RNAs (siRNAs) in a self-reinforcing cycle termed RNA-directed DNA methylation (RdDM). RdDM requires the specialized RNA polymerase V (Pol V), and the key unanswered question is how Pol V is first recruited to new target sites without pre-existing DNA methylation. We find that Pol V follows and is dependent on the recruitment of an AGO4-clade ARGONAUTE protein, and any siRNA can guide the ARGONAUTE
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14

Deans, Natalie C., Joy-El R. B. Talbot, Mowei Li, et al. "Paramutation at the maize pl1 locus is associated with RdDM activity at distal tandem repeats." PLOS Genetics 20, no. 5 (2024): e1011296. http://dx.doi.org/10.1371/journal.pgen.1011296.

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Exceptions to Mendelian inheritance often highlight novel chromosomal behaviors. The maize Pl1-Rhoades allele conferring plant pigmentation can display inheritance patterns deviating from Mendelian expectations in a behavior known as paramutation. However, the chromosome features mediating such exceptions remain unknown. Here we show that small RNA production reflecting RNA polymerase IV function within a distal downstream set of five tandem repeats is coincident with meiotically-heritable repression of the Pl1-Rhoades transcription unit. A related pl1 haplotype with three, but not one with tw
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15

Mishra, Vibhor, Jasleen Singh, Feng Wang, et al. "Assembly of a dsRNA synthesizing complex: RNA-DEPENDENT RNA POLYMERASE 2 contacts the largest subunit of NUCLEAR RNA POLYMERASE IV." Proceedings of the National Academy of Sciences 118, no. 13 (2021): e2019276118. http://dx.doi.org/10.1073/pnas.2019276118.

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In plants, transcription of selfish genetic elements such as transposons and DNA viruses is suppressed by RNA-directed DNA methylation. This process is guided by 24-nt short-interfering RNAs (siRNAs) whose double-stranded precursors are synthesized by DNA-dependent NUCLEAR RNA POLYMERASE IV (Pol IV) and RNA-DEPENDENT RNA POLYMERASE 2 (RDR2). Pol IV and RDR2 coimmunoprecipitate, and their activities are tightly coupled, yet the basis for their association is unknown. Here, we show that an interval near the RDR2 active site contacts the Pol IV catalytic subunit, NRPD1, the largest of Pol IV’s 12
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16

Manavella, Pablo. "DNA Topoisomerase 1α Promotes Transcriptional Silencing of Transposable Elements through DNA Methylation and Histone Lysine 9 Dimethylation in Arabidopsis". PLoS Genetics 10, № 7 (2014): e1004446. https://doi.org/10.1371/journal.pgen.1004446.

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RNA-directed DNA methylation (RdDM) and histone H3K9 dimethylation (H3K9me2) are related transcriptional silencing mechanisms that target transposable elements (TEs) and repeats to maintain genome stability in plants. RdDM is mediated by small and long noncoding RNAs produced by the plant-specific RNA polymerases Pol IV and Pol V, respectively. Through a chemical genetics screen with a luciferase-based DNA methylation reporter, LUCL, we found that camptothecin, a compound with anti- cancer properties that targets DNA topoisomerase 1α (TOP1α) was able to de-repress LUCL by reducing
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17

Gupta, Khushboo, and Rohini Garg. "Unravelling Differential DNA Methylation Patterns in Genotype Dependent Manner under Salinity Stress Response in Chickpea." International Journal of Molecular Sciences 24, no. 3 (2023): 1863. http://dx.doi.org/10.3390/ijms24031863.

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DNA methylation is one of the epigenetic mechanisms that govern gene regulation in response to abiotic stress in plants. Here, we analyzed the role of epigenetic variations by exploring global DNA methylation and integrating it with differential gene expression in response to salinity stress in tolerant and sensitive chickpea genotypes. Genome-wide DNA methylation profiles showed higher CG methylation in the gene body regions and higher CHH methylation in the TE body regions. The analysis of differentially methylated regions (DMRs) suggested more hyper-methylation in response to stress in the
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18

Huang, Kun, Xiao-Xian Wu, Cheng-Li Fang, et al. "Pol IV and RDR2: A two-RNA-polymerase machine that produces double-stranded RNA." Science 374, no. 6575 (2021): 1579–86. http://dx.doi.org/10.1126/science.abj9184.

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A tunnel between RNA polymerases Eukaryotes encode five multiple-subunit, DNA-dependent RNA polymerases, of which Pol I, Pol II, and Pol III function as single units to produce cellular single-stranded RNA. The plant-specific Pol IV forms a complex with RDR2 (an RNA-dependent RNA polymerase) to produce double-stranded precursors of small interfering RNA essential for genomic DNA methylation. Huang et al . determined the cryo–electron microscopy structures of the Pol IV-RDR2 complex. The structures show that Pol IV and RDR2 connect their active centers through an inner RNA transfer channel and
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19

Jackel, Jamie N., Jessica M. Storer, Tami Coursey, and David M. Bisaro. "Arabidopsis RNA Polymerases IV and V Are Required To Establish H3K9 Methylation, but Not Cytosine Methylation, on Geminivirus Chromatin." Journal of Virology 90, no. 16 (2016): 7529–40. http://dx.doi.org/10.1128/jvi.00656-16.

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ABSTRACTIn plants, RNA-directed DNA methylation (RdDM) employs small RNAs to target enzymes that methylate cytosine residues. Cytosine methylation and dimethylation of histone 3 lysine 9 (H3K9me2) are often linked. Together they condition an epigenetic defense that results in chromatin compaction and transcriptional silencing of transposons and viral chromatin. Canonical RdDM (Pol IV-RdDM), involving RNA polymerases IV and V (Pol IV and Pol V), was believed to be necessary to establish cytosine methylation, which in turn could recruit H3K9 methyltransferases. However, recent studies have revea
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20

Costa-Nunes, Pedro, Olga Pontes, Sasha B. Preuss, and Craig S. Pikaard. "Extra views on RNA-dependent DNA methylation and MBD6-dependent heterochromatin formation in nucleolar dominance." Nucleus 1, no. 3 (2010): 254–59. http://dx.doi.org/10.4161/nucl.11741.

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21

Costa-Nunes, Pedro, Olga Pontes, Sasha B. Preuss, and Craig S. Pikaard. "Extra views on RNA-dependent DNA methylation and MBD6-dependent heterochromatin formation in nucleolar dominance." Nucleus 1, no. 3 (2010): 254–59. http://dx.doi.org/10.4161/nucl.1.3.11741.

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22

Melnik, Bodo C., Ralf Weiskirchen, Wolfgang Stremmel, Swen Malte John, and Gerd Schmitz. "Risk of Fat Mass- and Obesity-Associated Gene-Dependent Obesogenic Programming by Formula Feeding Compared to Breastfeeding." Nutrients 16, no. 15 (2024): 2451. http://dx.doi.org/10.3390/nu16152451.

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It is the purpose of this review to compare differences in postnatal epigenetic programming at the level of DNA and RNA methylation and later obesity risk between infants receiving artificial formula feeding (FF) in contrast to natural breastfeeding (BF). FF bears the risk of aberrant epigenetic programming at the level of DNA methylation and enhances the expression of the RNA demethylase fat mass- and obesity-associated gene (FTO), pointing to further deviations in the RNA methylome. Based on a literature search through Web of Science, Google Scholar, and PubMed databases concerning the dieta
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Davletgildeeva, Anastasiia T., та Nikita A. Kuznetsov. "Dealkylation of Macromolecules by Eukaryotic α-Ketoglutarate-Dependent Dioxygenases from the AlkB-like Family". Current Issues in Molecular Biology 46, № 9 (2024): 10462–91. http://dx.doi.org/10.3390/cimb46090622.

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Alkylating modifications induced by either exogenous chemical agents or endogenous metabolites are some of the main types of damage to DNA, RNA, and proteins in the cell. Although research in recent decades has been almost entirely devoted to the repair of alkyl and in particular methyl DNA damage, more and more data lately suggest that the methylation of RNA bases plays an equally important role in normal functioning and in the development of diseases. Among the most prominent participants in the repair of methylation-induced DNA and RNA damage are human homologs of Escherichia coli AlkB, non
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Wang, Qi, Jie Xu, Xuemei Pu, et al. "Maize DNA Methylation in Response to Drought Stress Is Involved in Target Gene Expression and Alternative Splicing." International Journal of Molecular Sciences 22, no. 15 (2021): 8285. http://dx.doi.org/10.3390/ijms22158285.

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DNA methylation is important for plant growth, development, and stress response. To understand DNA methylation dynamics in maize roots under water stress (WS), we reanalyzed DNA methylation sequencing data to profile DNA methylation and the gene expression landscape of two inbred lines with different drought sensitivities, as well as two of their derived recombination inbred lines (RILs). Combined with genotyping-by-sequencing, we found that the inheritance pattern of DNA methylation between RILs and parental lines was sequence-dependent. Increased DNA methylation levels were observed under WS
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25

Mann, Jeffrey R., and Deidre M. Mattiske. "RNA interference in mammalian DNA methylation1This review is part of Special Issue entitled Asilomar Chromatin and has undergone the Journal’s usual peer review process." Biochemistry and Cell Biology 90, no. 1 (2012): 70–77. http://dx.doi.org/10.1139/o11-050.

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RNAi and Dicer-dependent siRNAs are required for constitutive heterochromatin formation in fission yeast and for establishing DNA methylation at repetitive elements in plants. In the mammalian male germ line, DICER1-independent piRNAs are required for the full establishment of DNA methylation of dispersed repetitive transposable elements. However, in other mammalian cell types, no clear picture has yet emerged of the role of RNAi in establishing heterochromatin and DNA methylation. In mouse embryonic stem cells, which remain viable on loss of DICER1 and ablation of RNAi, while no firm evidence
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26

D'Alessio, Ana C., Ian C. G. Weaver, and Moshe Szyf. "Acetylation-Induced Transcription Is Required for Active DNA Demethylation in Methylation-Silenced Genes." Molecular and Cellular Biology 27, no. 21 (2007): 7462–74. http://dx.doi.org/10.1128/mcb.01120-07.

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ABSTRACTA hallmark of vertebrate genes is that actively transcribed genes are hypomethylated in critical regulatory sequences. However, the mechanisms that link gene transcription and DNA hypomethylation are unclear. Using a trichostatin A (TSA)-induced replication-independent demethylation assay with HEK 293 cells, we show that RNA transcription is required for DNA demethylation. Histone acetylation precedes but is not sufficient to trigger DNA demethylation. Following histone acetylation, RNA polymerase II (RNAP II) interacts with the methylated promoter. Inhibition of RNAP II transcription
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27

Santoro, Raffaella, and Ingrid Grummt. "Epigenetic Mechanism of rRNA Gene Silencing: Temporal Order of NoRC-Mediated Histone Modification, Chromatin Remodeling, and DNA Methylation." Molecular and Cellular Biology 25, no. 7 (2005): 2539–46. http://dx.doi.org/10.1128/mcb.25.7.2539-2546.2005.

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ABSTRACT Epigenetic control mechanisms silence about half of the rRNA genes in eukaryotes. Previous studies have demonstrated that recruitment of NoRC, a SNF2h-containing remodeling complex, silences rRNA gene transcription. NoRC mediates histone H4 deacetylation, histone H3-Lys9 dimethylation, and de novo DNA methylation, thus establishing heterochromatic features at the rRNA gene promoter. Here we show that inhibition of any of these activities alleviates NoRC-dependent silencing, indicating that these processes are intimately linked. We have studied the temporal order of epigenetic events a
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28

Lyko, Frank. "RNA Methylation and Its Role in the Hematopoietic System." Blood 130, Suppl_1 (2017): SCI—52—SCI—52. http://dx.doi.org/10.1182/blood.v130.suppl_1.sci-52.sci-52.

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Abstract RNA methylation represents a novel expansion of traditional epigenetic concepts. RNAs can be methylated at adenine and at cytosine residues, and both modifications have distinct regulatory potential. Our work focuses on the DNMT2 enzyme, which is a member of the animal (cytosine-5) DNA methyltransferase family and has long been considered to function as a DNA methyltransferase. However, a DNA methyltransferase activity could not be confirmed conclusively and more recent work clearly demonstrates that DNMT2 is a tRNA methyltransferase. This unexpected substrate is interpreted to reflec
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29

Onodera, Yasuyuki, Jeremy R. Haag, Thomas Ream, Pedro Costa Nunes, Olga Pontes, and Craig S. Pikaard. "Plant Nuclear RNA Polymerase IV Mediates siRNA and DNA Methylation-Dependent Heterochromatin Formation." Cell 120, no. 5 (2005): 613–22. http://dx.doi.org/10.1016/j.cell.2005.02.007.

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30

Li, Qing, Jonathan I. Gent, Greg Zynda, et al. "RNA-directed DNA methylation enforces boundaries between heterochromatin and euchromatin in the maize genome." Proceedings of the National Academy of Sciences 112, no. 47 (2015): 14728–33. http://dx.doi.org/10.1073/pnas.1514680112.

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The maize genome is relatively large (∼2.3 Gb) and has a complex organization of interspersed genes and transposable elements, which necessitates frequent boundaries between different types of chromatin. The examination of maize genes and conserved noncoding sequences revealed that many of these are flanked by regions of elevated asymmetric CHH (where H is A, C, or T) methylation (termed mCHH islands). These mCHH islands are quite short (∼100 bp), are enriched near active genes, and often occur at the edge of the transposon that is located nearest to genes. The analysis of DNA methylation in o
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31

Dev, Rachana Roshan, Rakesh Ganji, Satya Prakash Singh, Sundarasamy Mahalingam, Sharmistha Banerjee, and Sanjeev Khosla. "Cytosine methylation by DNMT2 facilitates stability and survival of HIV-1 RNA in the host cell during infection." Biochemical Journal 474, no. 12 (2017): 2009–26. http://dx.doi.org/10.1042/bcj20170258.

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The enigmatic methyltransferase, DNMT2 (DNA methyltransferase 2), structurally resembles a DNA methyltransferase, but has been shown to be a tRNA methyltransferase targeting cytosine within a specific CpG in different tRNA molecules. We had previously shown that, during environmental stress conditions, DNMT2 is re-localized from the nucleus to the cytoplasmic stress granules (SGs) and is associated with RNA-processing proteins. In the present study, we show that DNMT2 binds and methylates various mRNA species in a sequence-independent manner and gets re-localized to SGs in a phosphorylation-de
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32

Grover, Jeffrey W., Diane Burgess, Timmy Kendall, et al. "Abundant expression of maternal siRNAs is a conserved feature of seed development." Proceedings of the National Academy of Sciences 117, no. 26 (2020): 15305–15. http://dx.doi.org/10.1073/pnas.2001332117.

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Small RNAs are abundant in plant reproductive tissues, especially 24-nucleotide (nt) small interfering RNAs (siRNAs). Most 24-nt siRNAs are dependent on RNA Pol IV and RNA-DEPENDENT RNA POLYMERASE 2 (RDR2) and establish DNA methylation at thousands of genomic loci in a process called RNA-directed DNA methylation (RdDM). InBrassica rapa, RdDM is required in the maternal sporophyte for successful seed development. Here, we demonstrate that a small number of siRNA loci account for over 90% of siRNA expression duringB. rapaseed development. These loci exhibit unique characteristics with regard to
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Jintaridth, Pornrutsami, and Apiwat Mutirangura. "Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences." Physiological Genomics 41, no. 2 (2010): 194–200. http://dx.doi.org/10.1152/physiolgenomics.00146.2009.

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Interspersed repetitive sequences (IRSs) are a major contributor to genome size and may contribute to cellular functions. IRSs are subdivided according to size and functionally related structures into short interspersed elements, long interspersed elements (LINEs), DNA transposons, and LTR-retrotransposons. Many IRSs may produce RNA and regulate genes by a variety of mechanisms. The majority of DNA methylation occurs in IRSs and is believed to suppress IRS activities. Global hypomethylation, or the loss of genome-wide methylation, is a common epigenetic event not only in senescent cells but al
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Zhuang, Qinwei Kim-Wee, Jose Hector Galvez, Qian Xiao, et al. "Sex Chromosomes and Sex Phenotype Contribute to Biased DNA Methylation in Mouse Liver." Cells 9, no. 6 (2020): 1436. http://dx.doi.org/10.3390/cells9061436.

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Sex biases in the genome-wide distribution of DNA methylation and gene expression levels are some of the manifestations of sexual dimorphism in mammals. To advance our understanding of the mechanisms that contribute to sex biases in DNA methylation and gene expression, we conducted whole genome bisulfite sequencing (WGBS) as well as RNA-seq on liver samples from mice with different combinations of sex phenotype and sex-chromosome complement. We compared groups of animals with different sex phenotypes, but the same genetic sexes, and vice versa, same sex phenotypes, but different sex-chromosome
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Vuu, Yen My, Chris-Tiann Roberts, and Mojgan Rastegar. "MeCP2 Is an Epigenetic Factor That Links DNA Methylation with Brain Metabolism." International Journal of Molecular Sciences 24, no. 4 (2023): 4218. http://dx.doi.org/10.3390/ijms24044218.

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DNA methylation, one of the most well-studied epigenetic modifications, is involved in a wide spectrum of biological processes. Epigenetic mechanisms control cellular morphology and function. Such regulatory mechanisms involve histone modifications, chromatin remodeling, DNA methylation, non-coding regulatory RNA molecules, and RNA modifications. One of the most well-studied epigenetic modifications is DNA methylation that plays key roles in development, health, and disease. Our brain is probably the most complex part of our body, with a high level of DNA methylation. A key protein that binds
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Pang, You-Yuan, Rita Jui-Hsien Lu, and Pao-Yang Chen. "Behavioral Epigenetics: Perspectives Based on Experience-Dependent Epigenetic Inheritance." Epigenomes 3, no. 3 (2019): 18. http://dx.doi.org/10.3390/epigenomes3030018.

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Epigenetic regulation plays an important role in gene regulation, and epigenetic markers such as DNA methylation and histone modifications are generally described as switches that regulate gene expression. Behavioral epigenetics is defined as the study of how epigenetic alterations induced by experience and environmental stress may affect animal behavior. It studies epigenetic alterations due to environmental enrichment. Generally, molecular processes underlying epigenetic regulation in behavioral epigenetics include DNA methylation, post-translational histone modifications, noncoding RNA acti
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Ferrafiat, Laura, David Pflieger, Jasleen Singh, et al. "The NRPD1 N-terminus contains a Pol IV-specific motif that is critical for genome surveillance in Arabidopsis." Nucleic Acids Research 47, no. 17 (2019): 9037–52. http://dx.doi.org/10.1093/nar/gkz618.

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Abstract RNA-guided surveillance systems constrain the activity of transposable elements (TEs) in host genomes. In plants, RNA polymerase IV (Pol IV) transcribes TEs into primary transcripts from which RDR2 synthesizes double-stranded RNA precursors for small interfering RNAs (siRNAs) that guide TE methylation and silencing. How the core subunits of Pol IV, homologs of RNA polymerase II subunits, diverged to support siRNA biogenesis in a TE-rich, repressive chromatin context is not well understood. Here we studied the N-terminus of Pol IV’s largest subunit, NRPD1. Arabidopsis lines harboring m
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Liang, Jing, Aishwarya Gondane, and Harri M. Itkonen. "Abstract 6412: Inactivation of CDK12 remodels the transcription machinery and promotes epigenetic plasticity." Cancer Research 85, no. 8_Supplement_1 (2025): 6412. https://doi.org/10.1158/1538-7445.am2025-6412.

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Abstract Background: Prostate cancer (PC) is the most common cancer in men, and inactivation of cyclin-dependent kinase 12 (CDK12) characterizes a subset of PCs but it is not understood how cells adapt to decline in the activity of this major transcription elongation kinase. CDK12 phosphorylates RNA polymerase II (RNA Pol II) to promote transcription elongation and cancer cells in general have high levels of transcription. It is therefore unexpected that the loss of CDK12 activity would confer a proliferative advantage. Methods and Results: We used PC patient data to probe if inactivation of t
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39

Bond, Donna M., and David C. Baulcombe. "Epigenetic transitions leading to heritable, RNA-mediated de novo silencing in Arabidopsis thaliana." Proceedings of the National Academy of Sciences 112, no. 3 (2015): 917–22. http://dx.doi.org/10.1073/pnas.1413053112.

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In plants, RNA-directed DNA methylation (RdDM), a mechanism where epigenetic modifiers are guided to target loci by small RNAs, plays a major role in silencing of transposable elements (TEs) to maintain genome integrity. So far, two RdDM pathways have been identified: RNA Polymerase IV (PolIV)-RdDM and RNA-dependent RNA Polymerase 6 (RDR6)-RdDM. PolIV-RdDM involves a self-reinforcing feedback mechanism that maintains TE silencing, but cannot explain how epigenetic silencing is first initiated. A function of RDR6-RdDM is to reestablish epigenetic silencing of active TEs, but it is unknown if th
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Jabre, Ibtissam, Saurabh Chaudhary, Cornelia M. Wilson, Dorothee Staiger, and Naeem Syed. "Stochastic Variation in DNA Methylation Modulates Nucleosome Occupancy and Alternative Splicing in Arabidopsis thaliana." Plants 11, no. 9 (2022): 1105. http://dx.doi.org/10.3390/plants11091105.

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Plants use complex gene regulatory mechanisms to overcome diverse environmental challenges. For instance, cold stress induces rapid and massive transcriptome changes via alternative splicing (AS) to confer cold tolerance in plants. In mammals, mounting evidence suggests chromatin structure can regulate co-transcriptional AS. Recent evidence also supports co-transcriptional regulation of AS in plants, but how dynamic changes in DNA methylation and the chromatin structure influence the AS process upon cold stress remains poorly understood. In this study, we used the DNA methylation inhibitor 5-A
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Thieme, Michael, Sophie Lanciano, Sandrine Balzergue, Nicolas Daccord, Marie Mirouze, and Etienne Bucher. "Inhibition of RNA polymerase II allows controlled mobilisation of retrotransposons for plant breeding." Genome Biology 18, no. 1 (2017): 134. https://doi.org/10.1186/s13059-017-1265-4.

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<strong>Background: </strong>Retrotransposons play a central role in plant evolution and could be a powerful endogenous source of genetic and epigenetic variability for crop breeding. To ensure genome integrity several silencing mechanisms have evolved to repress retrotransposon mobility. Even though retrotransposons fully depend on transcriptional activity of the host RNA polymerase II (Pol II) for their mobility, it was so far unclear whether Pol II is directly involved in repressing their activity.<strong>Results: </strong>Here we show that plants defective in Pol II activity lose DNA methy
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42

Coluccio, Andrea, Gabriela Ecco, Julien Duc, Sandra Offner, Priscilla Turelli, and Didier Trono. "Individual retrotransposon integrants are differentially controlled by KZFP/KAP1-dependent histone methylation, DNA methylation and TET-mediated hydroxymethylation in naïve embryonic stem cells." Epigenetics & Chromatin 11, no. 1 (2018): 7. https://doi.org/10.1186/s13072-018-0177-1.

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<strong>Background: </strong>The KZFP/KAP1 (KRAB zinc finger proteins/KRAB-associated protein 1) system plays a central role in repressing transposable elements (TEs) and maintaining parent-of-origin DNA methylation at imprinting control regions (ICRs) during the wave of genome-wide reprogramming that precedes implantation. In naïve murine embryonic stem cells (mESCs), the genome is maintained highly hypomethylated by a combination of TET-mediated active demethylation and lack of de novo methylation, yet KAP1 is tethered by sequence-specific KZFPs to ICRs and TEs where it recruits histone and
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Liu, Jun, Ge Bai, Cuijun Zhang, et al. "An atypical component of RNA-directed DNA methylation machinery has both DNA methylation-dependent and -independent roles in locus-specific transcriptional gene silencing." Cell Research 21, no. 12 (2011): 1691–700. http://dx.doi.org/10.1038/cr.2011.173.

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Jiang, Aiwen, Yangyang Ma, Xue Zhang, et al. "The Defects of Epigenetic Reprogramming in Dox-Dependent Porcine-iPSCs." International Journal of Molecular Sciences 23, no. 19 (2022): 11941. http://dx.doi.org/10.3390/ijms231911941.

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Porcine-induced pluripotent stem cells (piPSCs) are of great significance to animal breeding and human medicine; however, an important problem is that the maintenance of piPSCs mainly depends on exogenous expression of pluripotent transcription factors (TFs), and germline transmission-competent piPSCs have not yet been successfully established. In this study, we explore the defect of epigenetic reprogramming during piPSCs formation, including chromatin accessibility, DNA methylation, and imprinted gene expression, with high-throughput sequencing (ATAC-seq, WGBS, RNA-seq, and Re-seq) methods. W
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Vaistij, Fabián E., Louise Jones, and David C. Baulcombe. "Spreading of RNA Targeting and DNA Methylation in RNA Silencing Requires Transcription of the Target Gene and a Putative RNA-Dependent RNA Polymerase." Plant Cell 14, no. 4 (2002): 857–67. http://dx.doi.org/10.1105/tpc.010480.

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Wallecha, Anu, Vincent Munster, Jason Correnti, Teresa Chan, and Marjan van der Woude. "Dam- and OxyR-Dependent Phase Variation of agn43: Essential Elements and Evidence for a New Role of DNA Methylation." Journal of Bacteriology 184, no. 12 (2002): 3338–47. http://dx.doi.org/10.1128/jb.184.12.3338-3347.2002.

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ABSTRACT Phase variation of the outer membrane protein Ag43 in E. coli requires deoxyadenosine methylase (Dam) and OxyR. Previously, it was shown that OxyR is required for repression of the Ag43-encoding gene, agn43, and that Dam-dependent methylation of three GATC target sequences in the regulatory region abrogates OxyR binding. Here we report further characterization of agn43 transcription and its regulation. Transcription was initiated from a σ70-dependent promoter at the G residue of the upstream GATC sequence. Template DNA and RNA polymerase were sufficient to obtain transcription in vitr
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47

Du, Xuan. "The cellular RNA‐dependent RNA polymerases in plants." New Phytologist, August 13, 2024. http://dx.doi.org/10.1111/nph.20046.

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SummaryRNA‐dependent RNA Polymerases (RdRPs) synthesize double‐stranded RNA (dsRNA) from a single‐stranded RNA (ssRNA) template. In plants, dsRNAs produced by RdRPs can be further processed into small interfering RNA (siRNAs) with different lengths, ranging from 21 to 24 nucleotides (nt). These siRNAs play a pivotal role in various biological processes, including antiviral responses, transposable elements silencing, DNA methylation, and the regulation of plant reproduction and development. Recent research has reported significant progress in uncovering the molecular mechanisms of plant RNA‐DEP
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Lu, MA, Hatlen Andrea, J. Kelly Laura, et al. "ANGIOSPERMS ARE UNIQUE AMONGST LAND PLANT LINEAGES IN THE OCCURRENCE OF KEY GENES IN THE RNA DEPENDENT DNA METHYLATION (RDDM) PATHWAY." September 2, 2015. https://doi.org/10.1093/gbe/evv171.

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The RNA-directed DNA methylation pathway (RdDM) can be divided into three phases: (i) small interfering RNA biogenesis, (ii) <em>de novo </em>methylation and (iii) chromatin modification. To determine the degree of conservation of this pathway we searched for key genes amongst land plants. We used OrthoMCL and the OrthoMCL Viridiplantae database to analyse proteomes of species in bryophytes, lycophytes, monilophytes, gymnosperms and angiosperms. We also analysed small RNA size categories and, in two gymnosperms, cytosine methylation in ribosomal DNA. Six proteins were restricted to angiosperms
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Van Vu, Ba, Quyet Nguyen, Yuki Kondo-Takeoka, et al. "Copy number-dependent DNA methylation of the Pyricularia oryzae MAGGY retrotransposon is triggered by DNA damage." Communications Biology 4, no. 1 (2021). http://dx.doi.org/10.1038/s42003-021-01836-5.

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AbstractTransposable elements are common targets for transcriptional and post-transcriptional gene silencing in eukaryotic genomes. However, the molecular mechanisms responsible for sensing such repeated sequences in the genome remain largely unknown. Here, we show that machinery of homologous recombination (HR) and RNA silencing play cooperative roles in copy number-dependent de novo DNA methylation of the retrotransposon MAGGY in the fungusPyricularia oryzae. Genetic and physical interaction studies revealed thatRecAdomain-containing proteins, includingP. oryzaehomologs ofRad51, Rad55, andRa
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Fukudome, Akihito, Jasleen Singh, Vibhor Mishra, et al. "Structure and RNA template requirements of Arabidopsis RNA-DEPENDENT RNA POLYMERASE 2." Proceedings of the National Academy of Sciences 118, no. 51 (2021). http://dx.doi.org/10.1073/pnas.2115899118.

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Significance RDR2 is critical for siRNA-directed DNA methylation in Arabidopsis , functioning in physical association with DNA-dependent Pol IV to synthesize the second strands of double-stranded siRNA precursors. Base-pairing between the DNA template strand transcribed by Pol IV and the nontemplate DNA strand is needed to induce Pol IV arrest and Pol IV/RDR2 transcriptional coupling, but how this occurs is unknown. We report the structure of RDR2 and experimental evidence for how RDR2 engages its RNA templates and initiates transcription. RDR2 engages the ends of RNAs displaced from RNA/DNA h
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