Similar Datasets
Project description:Abstract: Cytosine DNA methylation plays crucial roles in gene regulation, transposon silencing, and diverse developmental processes. While methylation patterns are known to differ between cell-types, tissues, and disease states, how these differences arise remains poorly understood. In plants, DNA methylation is established via the RNA-directed DNA methylation pathway (RdDM), wherein 24-nucleotide small interfering RNAs (siRNAs) guide methylation at cognate genomic loci1. RNA POLYMERASE-IV (Pol-IV), a plant-specific polymerase, initiates the biogenesis of these methylation-targeting RNAs, thus understanding how Pol-IV is regulated is critical in determining how specific patterns of DNA methylation are generated. Here we show roles for four Pol-IV-associated factors, CLASSY (CLSY) 1-42,3, in both locus-specific and global regulation of Pol-IV function. Individually, each CLSY protein controls siRNA production and Pol-IV chromatin association at unique set of loci. This translates into locus-specific DNA methylation losses and the release of silencing. In addition to locus-specific effects, several layers of redundancy were identified: The clsy1,2 and clsy3,4 mutants act synergistically, regulating thousands more siRNA loci than the single mutants. Furthermore, the clsy1,2- and clsy3,4-dependent loci are mutually exclusive and geographically distinct, revealing a striking division of labor amongst the CLSY family. Finally, the clsy quadruple mutant causes global siRNA losses, demonstrating that Pol-IV is completely dependent on the CLSY family. Investigation into the mechanisms underlying the CLSY specificity revealed connections between clsy1,2- and clsy3,4-dependent loci and either SAWADEE HOMEODOMAIN HOMOLOG 1 or DNA METHYLTRANSFERASE 1, demonstrating a reliance on different chromatin modifications, H3K9 or CG DNA methylation, respectively4,5. Together, these findings not only shed light on Pol-IV function, but also reveal an additional layer of complexity to the RdDM pathway that enables the locus-specific control of DNA methylation patterns. Given the parallels between methylation systems in plants and mammals1, these findings will be informative for analogous processes in a broad range of organisms.
2018-04-14 | GSE99689 | GEO
Project description: Not available
| S-EPMC6317521 | biostudies-literature
Project description:Abstract: Cytosine DNA methylation plays crucial roles in gene regulation, transposon silencing, and diverse developmental processes. While methylation patterns are known to differ between cell-types, tissues, and disease states, how these differences arise remains poorly understood. In plants, DNA methylation is established via the RNA-directed DNA methylation pathway (RdDM), wherein 24-nucleotide small interfering RNAs (siRNAs) guide methylation at cognate genomic loci1. RNA POLYMERASE-IV (Pol-IV), a plant-specific polymerase, initiates the biogenesis of these methylation-targeting RNAs, thus understanding how Pol-IV is regulated is critical in determining how specific patterns of DNA methylation are generated. Here we show roles for four Pol-IV-associated factors, CLASSY (CLSY) 1-42,3, in both locus-specific and global regulation of Pol-IV function. Individually, each CLSY protein controls siRNA production and Pol-IV chromatin association at unique set of loci. This translates into locus-specific DNA methylation losses and the release of silencing. In addition to locus-specific effects, several layers of redundancy were identified: The clsy1,2 and clsy3,4 mutants act synergistically, regulating thousands more siRNA loci than the single mutants. Furthermore, the clsy1,2- and clsy3,4-dependent loci are mutually exclusive and geographically distinct, revealing a striking division of labor amongst the CLSY family. Finally, the clsy quadruple mutant causes global siRNA losses, demonstrating that Pol-IV is completely dependent on the CLSY family. Investigation into the mechanisms underlying the CLSY specificity revealed connections between clsy1,2- and clsy3,4-dependent loci and either SAWADEE HOMEODOMAIN HOMOLOG 1 or DNA METHYLTRANSFERASE 1, demonstrating a reliance on different chromatin modifications, H3K9 or CG DNA methylation, respectively4,5. Together, these findings not only shed light on Pol-IV function, but also reveal an additional layer of complexity to the RdDM pathway that enables the locus-specific control of DNA methylation patterns. Given the parallels between methylation systems in plants and mammals1, these findings will be informative for analogous processes in a broad range of organisms.
2018-04-14 | GSE99692 | GEO
Project description:Abstract: Cytosine DNA methylation plays crucial roles in gene regulation, transposon silencing, and diverse developmental processes. While methylation patterns are known to differ between cell-types, tissues, and disease states, how these differences arise remains poorly understood. In plants, DNA methylation is established via the RNA-directed DNA methylation pathway (RdDM), wherein 24-nucleotide small interfering RNAs (siRNAs) guide methylation at cognate genomic loci1. RNA POLYMERASE-IV (Pol-IV), a plant-specific polymerase, initiates the biogenesis of these methylation-targeting RNAs, thus understanding how Pol-IV is regulated is critical in determining how specific patterns of DNA methylation are generated. Here we show roles for four Pol-IV-associated factors, CLASSY (CLSY) 1-42,3, in both locus-specific and global regulation of Pol-IV function. Individually, each CLSY protein controls siRNA production and Pol-IV chromatin association at unique set of loci. This translates into locus-specific DNA methylation losses and the release of silencing. In addition to locus-specific effects, several layers of redundancy were identified: The clsy1,2 and clsy3,4 mutants act synergistically, regulating thousands more siRNA loci than the single mutants. Furthermore, the clsy1,2- and clsy3,4-dependent loci are mutually exclusive and geographically distinct, revealing a striking division of labor amongst the CLSY family. Finally, the clsy quadruple mutant causes global siRNA losses, demonstrating that Pol-IV is completely dependent on the CLSY family. Investigation into the mechanisms underlying the CLSY specificity revealed connections between clsy1,2- and clsy3,4-dependent loci and either SAWADEE HOMEODOMAIN HOMOLOG 1 or DNA METHYLTRANSFERASE 1, demonstrating a reliance on different chromatin modifications, H3K9 or CG DNA methylation, respectively4,5. Together, these findings not only shed light on Pol-IV function, but also reveal an additional layer of complexity to the RdDM pathway that enables the locus-specific control of DNA methylation patterns. Given the parallels between methylation systems in plants and mammals1, these findings will be informative for analogous processes in a broad range of organisms.
2018-04-14 | GSE99691 | GEO
Project description:Abstract: Cytosine DNA methylation plays crucial roles in gene regulation, transposon silencing, and diverse developmental processes. While methylation patterns are known to differ between cell-types, tissues, and disease states, how these differences arise remains poorly understood. In plants, DNA methylation is established via the RNA-directed DNA methylation pathway (RdDM), wherein 24-nucleotide small interfering RNAs (siRNAs) guide methylation at cognate genomic loci1. RNA POLYMERASE-IV (Pol-IV), a plant-specific polymerase, initiates the biogenesis of these methylation-targeting RNAs, thus understanding how Pol-IV is regulated is critical in determining how specific patterns of DNA methylation are generated. Here we show roles for four Pol-IV-associated factors, CLASSY (CLSY) 1-42,3, in both locus-specific and global regulation of Pol-IV function. Individually, each CLSY protein controls siRNA production and Pol-IV chromatin association at unique set of loci. This translates into locus-specific DNA methylation losses and the release of silencing. In addition to locus-specific effects, several layers of redundancy were identified: The clsy1,2 and clsy3,4 mutants act synergistically, regulating thousands more siRNA loci than the single mutants. Furthermore, the clsy1,2- and clsy3,4-dependent loci are mutually exclusive and geographically distinct, revealing a striking division of labor amongst the CLSY family. Finally, the clsy quadruple mutant causes global siRNA losses, demonstrating that Pol-IV is completely dependent on the CLSY family. Investigation into the mechanisms underlying the CLSY specificity revealed connections between clsy1,2- and clsy3,4-dependent loci and either SAWADEE HOMEODOMAIN HOMOLOG 1 or DNA METHYLTRANSFERASE 1, demonstrating a reliance on different chromatin modifications, H3K9 or CG DNA methylation, respectively4,5. Together, these findings not only shed light on Pol-IV function, but also reveal an additional layer of complexity to the RdDM pathway that enables the locus-specific control of DNA methylation patterns. Given the parallels between methylation systems in plants and mammals1, these findings will be informative for analogous processes in a broad range of organisms.
2018-04-14 | GSE99693 | GEO
Project description:Locus-specific control of the de novo DNA methylation pathway
| PRJNA389306 | ENA
Project description: Not available
| S-EPMC8185639 | biostudies-literature
Project description:DNA methylation by de novo DNA methyltransferases 3A (DNMT3A) and 3B (DNMT3B) is essential for genome regulation and development. Dysregulation of this process is implicated in various diseases, notably cancer. However, the mechanisms underlying DNMT3 substrate recognition and enzymatic specificity remain elusive. Here we report a 2.65-Å crystal structure of the DNMT3A-DNMT3L-DNA complex where two DNMT3A monomers simultaneously attack two CpG dinucleotides, with the target sites separated by fourteen base pairs within the same DNA duplex. The DNMT3A-DNA interaction involves a target recognition domain (TRD), a catalytic loop and DNMT3A homodimeric interface. A TRD residue Arg836 makes crucial contact with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. Hematological cancer-associated somatic mutations at the substrate-binding sites decrease DNMT3A activity, induce CpG hypomethylation and promote transformation of hematopoietic cells. Together, our study reveals the mechanistic basis for DNMT3A-mediated DNA methylation and establishes its etiologic link to human disease.
2018-01-01 | GSE99391 | GEO
Project description: Not available
| S-EPMC3368507 | biostudies-literature
Project description: Not available
| S-EPMC5989421 | biostudies-literature