RNA-mediated epigenetic regulation of gene expression

Holoch, Daniel; Moazed, Danesh

doi:10.1038/nrg3863

Cited by 898 publications

(732 citation statements)

References 166 publications

(238 reference statements)

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“…Non-coding RNA-mediated transcriptional gene silencing and heterochromatin formation has been observed in many organisms [16][17][18]. In all cases, small interfering RNAs (siRNAs) were thought to provide the targeting specificity for the enzymes that catalyze repressive epigenetic modifications [16].…”

Section: Introductionmentioning

confidence: 99%

“…In all cases, small interfering RNAs (siRNAs) were thought to provide the targeting specificity for the enzymes that catalyze repressive epigenetic modifications [16]. RdDM represents a major RNA-mediated epigenetic silencing pathway in npg www.cell-research.com | Cell Research plants [19], and has been proposed to proceed through at least two sequential steps: 24-nt siRNA biogenesis and siRNA-guided de novo methylation.…”

Section: Introductionmentioning

confidence: 99%

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Dicer-independent RNA-directed DNA methylation in Arabidopsis

et al. 2015

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RNA-directed DNA methylation (RdDM) is an important de novo DNA methylation pathway in plants. Small interfering RNAs (siRNAs) generated by Dicers from RNA polymerase IV (Pol IV) transcripts are thought to guide sequence-specific DNA methylation. To gain insight into the mechanism of RdDM, we performed whole-genome bisulfite sequencing of a collection of Arabidopsis mutants, including plants deficient in Pol IV (nrpd1) or Dicer (dcl1/2/3/4) activity. Unexpectedly, of the RdDM target loci that required Pol IV and/or Pol V, only 16% were fully dependent on Dicer activity. DNA methylation was partly or completely independent of Dicer activity at the remaining Pol IV-and/ or Pol V-dependent loci, despite the loss of 24-nt siRNAs. Instead, DNA methylation levels correlated with the accumulation of Pol IV-dependent 25-50 nt RNAs at most loci in Dicer mutant plants. Our results suggest that RdDM in plants is largely guided by a previously unappreciated class of Dicer-independent non-coding RNAs, and that siRNAs are required to maintain DNA methylation at only a subset of loci.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dicer-independent RNA-directed DNA methylation in Arabidopsis

et al. 2015

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“…Tandem repeats are usually present as constitutive heterochromatic loci (31)(32)(33). This can be associated with the presence of CpG methylation, which can act as a repressive epigenetic mark in some contexts (34). Cytosine methylation makes the base susceptible to deamination, resulting in C-to-T transitions (35,36).…”

Section: Resultsmentioning

confidence: 99%

Genome and transcriptome of the regeneration-competent flatworm, Macrostomum lignano

Wasik

Gurtowski

Zhou

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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The free-living flatworm, Macrostomum lignano has an impressive regenerative capacity. Following injury, it can regenerate almost an entirely new organism because of the presence of an abundant somatic stem cell population, the neoblasts. This set of unique properties makes many flatworms attractive organisms for studying the evolution of pathways involved in tissue self-renewal, cellfate specification, and regeneration. The use of these organisms as models, however, is hampered by the lack of a well-assembled and annotated genome sequences, fundamental to modern genetic and molecular studies. Here we report the genomic sequence of M. lignano and an accompanying characterization of its transcriptome. The genome structure of M. lignano is remarkably complex, with ∼75% of its sequence being comprised of simple repeats and transposon sequences. This has made high-quality assembly from Illumina reads alone impossible (N50 = 222 bp). We therefore generated 130× coverage by long sequencing reads from the Pacific Biosciences platform to create a substantially improved assembly with an N50 of 64 Kbp. We complemented the reference genome with an assembled and annotated transcriptome, and used both of these datasets in combination to probe gene-expression patterns during regeneration, examining pathways important to stem cell function.F latworms belong to the superphylum Lophotrochozoa, a vast assembly of protostome invertebrates (1, 2) (Fig. 1A). The evolutionary relationships within this clade are poorly resolved and the specific position of flatworms is currently debated (3, 4). Flatworms have attracted scientific attention for centuries because of their astonishing regenerative capabilities (5, 6), as well as their ability to "degrow" in a controlled way when starved (7). As far back as the early 1900s, Thomas Morgan recognized the potential of flatworms and conducted a number of fascinating regeneration experiments on planarian flatworms before his focus shifted to Drosophila genetics (8).Macrostomum lignano is (Fig. 1B), a free-living, regenerating flatworm isolated from the coast of the Mediterranean Sea. M. lignano is an obligatorily cross-fertilizing simultaneous hermaphrodite (9) that belongs to Macrostomorpha, whereas the other often-studied freeliving flatworms and human parasitic flatworms all belong to clades that are potentially more derived (less ancestral) in comparison with Macrostomorpha (2) (Fig. 1C).Many flatworms can regenerate nearly their entire body or amputated organs. This regenerative capacity is thought to be attributable to the presence of somatic stem cells, termed neoblasts (10, 11). In Schmidtea mediterranea (planarian flatworm), even a single transplanted neoblast has the ability to rescue, regenerate, and change the genotype of a fatally irradiated worm (12). M. lignano can regenerate every tissue, with the exception of the head region containing the brain (13,14).Neoblasts in M. lignano ( Fig. 1 D and E), in contrast to most vertebrate somatic stem cells, are plentiful, making up about ...

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“…2). However, for some genes, transcriptional states established early in development can be maintained through mitotic divisions by epigenetic mechanisms 40 . Furthermore, epigenetic crosstalk 41,42 , for example a positive feedback loop between chromatin and small RNAs, can promote long-term epigenetic memory in some organisms 40 , but again this field remains highly understudied in corals.…”

Section: Box 1 | the Pace Of Genetic Adaptationmentioning

confidence: 99%