RNA meets chromatin

Abstract

In the universe of science, two worlds have recently collided-those of RNA and chromatin. The intersection of these two fields has been impending, but evidence for such a meaningful collision has only recently become apparent. In this review, we discuss the implications for noncoding RNAs and the formation of specialized chromatin domains in various epigenetic processes as diverse as dosage compensation, RNA interference-mediated heterochromatin assembly and gene silencing, and programmed DNA elimination. While mechanistic details as to how the RNA and chromatin worlds connect remain unclear, intriguing parallels exist in the overall design and machinery used in model organisms from all eukaryotic kingdoms. The role of potential RNA-binding chromatin-associated proteins will be discussed as one possible link between RNA and chromatin.Chromatin, the intimate association of histone proteins and DNA into repeating nucleosomal units, is the physiologically relevant structure of our genome. An increasing body of evidence suggests that variation can be introduced into the chromatin polymer by an elaborate set of mechanisms that fail to alter the DNA template itself. The inheritance of chromatin states such as "active" (euchromatic) or "silent" (heterochromatic) domains forms the foundation of epigenetics. Until recently, understanding how, if at all, noncoding RNAs fit into the chromatin world, by influencing either euchromatin or heterochromatin, remained a puzzle that most biologists had simply not considered. Although the underlying mechanisms linking RNA and chromatin remain unclear, understanding how these epigenetic states are established and maintained during the life of a cell or development of an organism is imperative.We favor the general view that a complete appreciation of epigenetic regulation is likely to require a careful examination of both RNA and chromatin fields. One goal of this review is to expose potential links between these two research areas, with a focus on transcriptional gene silencing in a wide range of experimental models.We conclude with a speculative model for how a group of heterochromatin-associated proteins may participate in linking RNA and chromatin.

Dicer-independent RNA-directed DNA methylation in Arabidopsis

“…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].…”

Dynamic and reversibility of heterochromatic gene silencing in human disease

“…Loss of imprinting of H19/IGF-2 locus in some childhood tumors is a typical example (reviewed in [90]). DNA hypomethylation is also responsible for reactivation of transposable elements and silenced viral sequences, via erratic insertion of DNA fragments into transcribed regions or through a siRNA pathway [9,92]. Moreover, a diet deficient in folate, a vitamin involved in AdoMet metabolism, is associated with DNA hypomethylation and hepatocarcinogenesis in murine (reviewed in [93]).…”

Satellite DNA in insects: a review

“…The transcripts of the tandemrepeat centromeric DNA of the fission yeast Schizosaccharomyces pombe have been found to be clearly involved in RNA interference (RNAi)-mediated heterochromatin assembly. Similarly, recent data on DNA elimination in the ciliated protozoans Tetrahymena and Paramecium appear to indicate that it occurs via an RNAi-like mechanism (reviewed by Bernstein and Allis, 2005). However, there are many aspects that remain unknown about these processes.…”