Forgetting in C. elegans Is Accelerated by Neuronal Communication via the TIR-1/JNK-1 Pathway

The control of memory retention is important for proper responses to constantly changing environments, but the regulatory mechanisms underlying forgetting have not been fully elucidated. Our genetic analyses in C. elegans revealed that mutants of the TIR-1/JNK-1 pathway exhibited prolonged retention of olfactory adaptation and salt chemotaxis learning. In olfactory adaptation, conditioning induces attenuation of odor-evoked Ca2+ responses in olfactory neurons, and this attenuation is prolonged in the TIR-1/JNK-1-pathway mutant animals. We also found that a pair of neurons in which the pathway functions is required for the acceleration of forgetting, but not for sensation or adaptation, in wild-type animals. In addition, the neurosecretion from these cells is important for the acceleration of forgetting. Therefore, we propose that these neurons accelerate forgetting through the TIR-1/JNK-1 pathway by sending signals that directly or indirectly stimulate forgetting.

Akitoshi Inoue, et al

Cell Reports, Volume 3, Issue 3, 808-819, 21 March 2013

10.1016/j.celrep.2013.02.019

piRNAs Can Trigger a Multigenerational Epigenetic Memory in the Germline of C. elegans

Transgenerational effects have wide-ranging implications for human health, biological adaptation, and evolution; however, their mechanisms and biology remain poorly understood. Here, we demonstrate that a germline nuclear small RNA/chromatin pathway can maintain stable inheritance for many generations when triggered by a piRNA-dependent foreign RNA response in C. elegans. Using forward genetic screens and candidate approaches, we find that a core set of nuclear RNAi and chromatin factors is required for multigenerational inheritance of environmental RNAi and piRNA silencing. These include a germline-specific nuclear Argonaute HRDE1/WAGO-9, a HP1 ortholog HPL-2, and two putative histone methyltransferases, SET-25 and SET-32. piRNAs can trigger highly stable long-term silencing lasting at least 20 generations. Once established, this long-term memory becomes independent of the piRNA trigger but remains dependent on the nuclear RNAi/chromatin pathway. Our data present a multigenerational epigenetic inheritance mechanism induced by piRNAs.

Alyson Ashe et al.

Cell. 2012 July 6; 150(1): 88–99.
doi: 10.1016/j.cell.2012.06.018

Neural development: Epigenetic regulation of asymmetry

The brains of many species demonstrate structural and functional bilateral asymmetry, yet the underlying molecular mechanisms are mostly unknown. In the Caenorhabditis elegans nervous system, the lineages arising from the two daughter cells of a particular blastomere known as ABarap produce a different cell on each side of the body: a motor neuron on the right and an epithelial cell on the left. Here, the authors show that the CAF-1 (chromatin assembly factor-1) protein complex, a histone chaperone that deposits histone H3 and H4 proteins onto replicating DNA, is required to establish this asymmetry, suggesting a role for epigenetic regulation in the generation of nervous system asymmetry.

Nature Reviews Neuroscience 13, 72 (February 2012) | doi:10.1038/nrn3183
IN BRIEF:Neural development: Epigenetic regulation of asymmetry
Katherine Whalley

Nakano, S. et al. 

Replication-coupled chromatin assembly generates a neuronal bilateral asymmetry in C. elegans. 

Cell 147, 1525–1536 (2011)

Epigenetics in C. elegans: Facts and challenges

Epigenetics is defined as the study of heritable changes in gene expression that are not accompanied by changes in the DNA sequence. Epigenetic mechanisms include histone post-translational modifications, histone variant incorporation, non-coding RNAs, and nucleosome remodeling and exchange. In addition, the functional compartmentalization of the nucleus also contributes to epigenetic regulation of gene expression. Studies on the molecular mechanisms underlying epigenetic phenomena and their biological function have relied on various model systems, including yeast, plants, flies, and cultured mammalian cells. Here we will expose the reader to the current understanding of epigenetic regulation in the roundworm C. elegans. We will review recent models of nuclear organization and its impact on gene expression, the biological role of enzymes modifying core histones, and the function of chromatin-associated factors, with special emphasis on Polycomb (PcG) and Trithorax (Trx-G) group proteins. We will discuss how the C. elegans model has provided novel insight into mechanisms of epigenetic regulation as well as suggest directions for future research.

Dirk Wenze et al.
genesis 49:647–661, 2011.