Equal Parts of Plants, Fungi, and Metazoa

The field of epigenetics addresses the control mechanisms superimposed on primary DNA sequences. When the Epigenetics Gordon Research Conference was first proposed in 1994, the importance of epigenetic effects in gene regulation was only beginning to be appreciated. The first conference, organized by Timothy Bestor and myself, was held at the Holderness School in Plymouth, New Hampshire, in 1995.

Three people working on epigenetic effects on gene expression–Robert Martienssen, Amar Klar, and Bestor–contacted me in 1994 asking if I would be willing to help organize a Gordon Conference on epigenetics. There had previously been only one open meeting on this subject–a Keystone Symposium, organized by Shirley Tilghman and held in October 1993, which em-phasized genomic imprinting in mice and humans. A few small meetings brought together people working on different systems who shared an interest in epigenetics. We all felt that the time was ripe for a regular, open meeting and that the format of GRC would be perfect. The GRC proposal that Tim and I wrote was approved, with enthusiastic support from Nina Fedoroff, Joachim Messing, Martienssen, and Richard Jorgensen, who were all working with plants; Jasper Rine, Eric Selker, and Jean-Luc Rossignol, who were working with fungi; and Tilghman, Davor Solter, and Steven Henikoff, who were working with animals.

Ninety people attended the first meeting; there were twenty-nine speakers, and about fifty posters were presented. We met our goal of bringing together scientists who had related interests but little opportunity to interact by including equal numbers of scientists who studied plants, fungi, and metazoa. The participants were very enthusiastic about the meeting and voted to hold another one in 1997. The participants also voted that there would be two cochairs per conference, each of whom worked with a different organism, to continue broad representation at future meetings.

For the past ten years organizers of the Epigenetics Gordon Conference have kept with the themes established at the first meeting: successfully bringing together sci-entists studying epigenetics in diverse organisms like mammals, plants, fungi, insects, protozoa, and prokaryotes; focusing the meeting on genetic and developmental consequences of epigenetic effects; exploring molecular similarities among seemingly diverse phenomena; and encouraging the presentation of findings that would be deemed “weird” at most other meetings. It is clear that many seemingly diverse phenomena in different species share common underlying mechanisms. At the 2005 meeting speakers were instructed by the organizers, Chao-Ting Wu and Judith Bender, to push the envelope and speculate with no holds barred about the implications of their research, resulting in the most stimulating, thought-provoking Epigenetics GRC to date.

Looking back at the program for the first conference is illuminating. Major emphasis was placed on gene silencing in plants, animals, and humans. Conferees were des-cribing the phenomenology and looking for common themes but at that point had little understanding on a molecular level. In the years since, the molecular mechanisms underlying the phenomenological topics have begun to emerge, and other conference topics reveal more mechanistic understandings.

Changes in the field are revealed by examining what was not on the radar screen ten years ago. A dramatic example is the discovery that RNAi (RNA interference) in the nematode worm Caenorhabditis elegans and quelling (gene silencing in fungi) in molds of the genus Neurospora are mechanistically equivalent to post-transcriptional gene silencing and co-suppression in plants. RNA-mediated silencing featured prominently in subsequent meetings. Another example is that in 1995 we knew about histone modifications, but the major focus was on histone acetylation and deacetylation. Research on histone methylation, which received little attention in the early years, has exploded.

The Epigenetics GRC draws on many fields. Jean Finnegan, the 1997 cochair, relayed to me a memory of a dinner at the first conference where Klar, whose area of expertise was yeast genetics, asked everyone at the table, as well as the puzzled wait staff, whether they and their family members were left- or right-handed. Fascination with the genetic control of handedness has matured over the years, and at the 2005 meeting Klar presented the hypothesis that segregation of differentially marked DNA strands could contribute to handedness and certain human diseases.

Rob Martienssen, who cochaired the 2001 meeting, told me about how Rich Jorgensen made an offhand remark in his talk at the same conference that post-transcriptional gene silencing in plants seemed to occur on polysomes (polyribosomes, or several ribosomes configured to simultaneously translate the same messenger RNA). Rob wondered whether the argonaute proteins might be involved in gene silencing. That evening Andy Fire gave a talk on RNAi in C. elegans. Just prior to that, Craig Mello had called to tell him the identity of rde1, a gene required for RNAi, so Andy wrote it on a slide that he showed in his talk. It was argonaute! Rob had been working with the ago1 (argonaute) gene in plants for some time, and more recently in Schizosaccharomyces pombe (fission yeast). He grabbed Andy to show him pictures of plants and yeast: it was a moment Rob will not forget.

The Epigenetics GRC is a truly multidisciplinary conference. Epigenetics has be-come a field unto itself by the gathering at this meeting of scientists who have been able to compare and contrast their epigenetics research for a variety of organisms.