Insights from Keystone: advances in the understanding of epigenetic regulation of the genome

At the Keystone symposium in Breckenridge over 200 participants gathered to explore epigenetic control of genome function through various model systems and biological processes. Topics touched on were chromatin dynamics, epigenetic mechanisms and regulation and environmental and disease influences on epigenetic states. Here we report some highlights of the meeting.Bradley R Cairns (Huntsman Cancer Institute, Salt Lake City, USA) presented data showing that active DNA demethylation involves regulated coupling of deamination and base excision. Using a zebrafish demethylation assay system, he showed that activation-induced deaminase (AID) and methyl-CpG binding domain protein (MBD4) together cause genome-wide demethylation. Another factor that is involved in demethylation is Gadd45, which plays two roles: up-regulating transcription of the deaminase, as well as increasing interactions between AID and MBD4.Steven Henikoff (Fred Hutchinson Cancer Research Center, Seattle, USA) spoke on histone variants and chromatin dynamics. Centromeric H3 has functional conservation between Drosophila, Arabidopsis and Caenorhabditis elegans, with no real sequence conservation. Phylogeny analysis showed a clustering of the H3 core (Drosophila and human 100% identical) and CenH3s as outliers. He spoke on investigating what possible structural regions are responsible for the differences in conservation.Novel roles for core histone acetylation on H3K56 in longevity and tumorigenesis were described in a talk by Jessica K Tyler (University of Colorado Denver Health Sciences Center, USA). She summarized that the acetylation of H3K56 drives chromatin disassembly and reassembly at promoter regions, and chromatin assembly after DNA synthesis, and plays an important role in maintaining a normal life span in yeast.Geneviève Almouzni (Institut Curie, Paris, France) gave an interesting talk on the challenges of DNA replication and repair and the roles of chromatin assembly factors in these processes