Small RNAs Worm Up Transgenerational Epigenetics Research.

Alla Grishok

doi:10.3390/dna1020005

Abstract

DNA is central to the propagation and evolution of most living organisms due to the essential process of its self-replication. Yet it also encodes factors that permit epigenetic (not included in DNA sequence) flow of information from parents to their offspring and beyond. The known mechanisms of epigenetic inheritance include chemical modifications of DNA and chromatin, as well as regulatory RNAs. All these factors can modulate gene expression programs in the ensuing generations. The nematode Caenorhabditis elegans is recognized as a pioneer organism in transgenerational epigenetic inheritance research. Recent advances in C. elegans epigenetics include the discoveries of control mechanisms that limit the duration of RNA-based epigenetic inheritance, periodic DNA motifs that counteract epigenetic silencing establishment, new mechanistic insights into epigenetic inheritance carried by sperm, and the tantalizing examples of inheritance of sensory experiences. This review aims to highlight new findings in epigenetics research in C. elegans with the main focus on transgenerational epigenetic phenomena dependent on small RNAs.

Highlights

This review aims to highlight new findings in epigenetics research in C. elegans with the main focus on transgenerational epigenetic phenomena dependent on small RNAs
In the last 10–15 years, transgenerational epigenetic inheritance (TEI) phenomena have been described in the context of gene silencing induced by endogenous Piwi-interacting RNAs (Figure 2), and a broad term to describe long-lasting silencing has been introduced: RNA-induced epigenetic silencing (RNAe) [36,38,39]
The importance of small RNAs in transgenerational transgene silencing and in aberrant progressive silencing of endogenous genes, which underlies the mortal germline phenotype (Mrt) phenotype, is well documented

Summary

Introduction

Numerous discoveries in basic science were facilitated by the model organism Caenorhabditis elegans (reviewed in [1]) (Figure 1). The connection between the human diet and epigenetic adaptation to existing conditions via heritable RNA transmission in sperm (reviewed in [7]) underscores the importance of lessons learned from C. elegans This manuscript provides an overview of key findings that may interest a wide scientific audience, including the highlights from the Genetics Society of America 23rd. Other systems were made possible by technical advances in transgenic technology that allowed stable expression of transgenic arrays in the C. elegans germline [29] This allowed investigators to monitor germline GFP transgene silencing in the progeny of animals exposed to dsRNA, which was shown to last up to twenty generations with selection [30,31]. But not all [37], subsequent studies researching mechanisms of TEI in C. elegans utilized the oma-1 and/or germline GFP readouts

RNA-Based and Chromatin-Based Epigenetic Silencing and Their Connections

Permanent and Limited Forms of TEI and Their Genetic Control

Epigenetics of Holocentric Centromeres

DNA “Watermarks” Allowing Gene Expression in Silenced

Concluding Remarks