The freshwater cnidarian Hydra was first described in 17021 and has been the object of study for 300 years. Experimental studies of Hydra between 1736 and 1744 culminated in the discovery of asexual reproduction of an animal by budding, the first description of regeneration in an animal, and successful transplantation of tissue between animals2. Today, Hydra is an important model for studies of axial patterning3, stem cell biology4 and regeneration5. Here we report the genome of Hydra magnipapillata and compare it to the genomes of the anthozoan Nematostella vectensis6 and other animals. The Hydra genome has been shaped by bursts of transposable element expansion, horizontal gene transfer, trans-splicing, and simplification of gene structure and gene content that parallel simplification of the Hydra life cycle. We also report the sequence of the genome of a novel bacterium stably associated with H. magnipapillata. Comparisons of the Hydra genome to the genomes of other animals shed light on the evolution of epithelia, contractile tissues, developmentally regulated transcription factors, the Spemann–Mangold organizer, pluripotency genes and the neuromuscular junction.

10. These authors contributed equally to the work.11. These authors contributed equally to the work. AbstractThe metazoan hypoxic response is regulated by the oxygen-dependent posttranslational hydroxylation of the -subunits of the hypoxia inducible factor (HIF)system. This identification has raised the question of whether other proteinhydroxylases are involved in the regulation of gene expression. Here we demonstrate that the splicing factor protein U2AF65 undergoes post-translational lysyl-5-hydroxylation as catalysed by the Fe(II) and 2-oxoglutarate dependent dioxygenaseJumonji domain-containing protein 6 (Jmjd6). Jmjd6 is a nuclear protein that has an important role in vertebrate development and is a close human homologue of the hypoxia inducible factor asparaginyl-hydroxylase. Jmjd6 is shown to regulate alternative RNA splicing of endogenous and reporter genes. The ability of Jmjd6 to influence the splicing pattern of all endogenous genes investigated supports a specific role for Jmjd6 in regulating RNA splicing. Main textMetazoan cells respond to limiting oxygen by activation of the hypoxia inducible factor (HIF) system(1). The HIF subunits are regulated by Fe(II) and 2-oxoglutarate

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These results demonstrate that the p53 response is constitutively regulated in normal cells by Mdm2 and that disruption of the interaction alone is sufficient to stabilise the p53 protein and activate the p53 response. Our mini protein approach provides a powerful new method to activate p53 without causing DNA damage. More broadly, it establishes a powerful general method for determining the biological consequences of the specific disruption of protein-protein interactions in cells.

Mdm2 and MDMX are two structurally related p53-binding proteins which show the highest level of sequence similarity in the N-terminal p53-binding domains. Apart from its ability to inhibit p53 mediated transcription, a feature it shares with mdm2, very little is known about the physiological functions of MDMX. It is clearly distinct from mdm2 since its expression appears not to be regulated by p53 and it cannot compensate for lack of mdm2 in early development. We present data on the structural similarity between the p53 binding pockets of mdm2 and MDMX using p53-and phage-selected peptides. From the results we conclude that our recently devised innovative approach to reverse the mdm2-mediated inhibition of p53's transactivation function in vivo would probably target MDMX as well. Strategies for selectively targeting mdm2 and MDMX are suggested and a possible mechanism for regulating the p53-mdm2/MDMX interactions by protein phosphorylation is discussed.