Imprinting on distal chromosome 7 in the placenta involves repressive histone methylation independent of DNA methylation

Imprinted genes are expressed from only one of the parental chromosomes and are marked epigenetically by DNA methylation and histone modifications. The imprinting center 2 (IC2) on mouse distal chromosome 7 is flanked by several paternally repressed genes, with the more distant ones imprinted exclusively in the placenta. We found that most of these genes lack parent-specific DNA methylation, and genetic ablation of methylation does not lead to loss of their imprinting in the trophoblast (placenta). The silent paternal alleles of the genes are marked in the trophoblast by repressive histone modifications (dimethylation at Lys9 of histone H3 and trimethylation at Lys27 of histone H3), which are disrupted when IC2 is deleted, leading to reactivation of the paternal alleles. Thus, repressive histone methylation is recruited by IC2 (potentially through a noncoding antisense RNA) to the paternal chromosome in a region of at least 700 kb and maintains imprinting in this cluster in the placenta, independently of DNA methylation. We propose that an evolutionarily older imprinting mechanism limited to extraembryonic tissues was based on histone modifications, and that this mechanism was subsequently made more stable for use in embryonic lineages by the recruitment of DNA methylation.     

Vernalization requires epigenetic silencing of FLC by histone methylation

To ensure flowering in favourable conditions, many plants flower only after an extended period of cold, namely winter. In Arabidopsis, the acceleration of flowering by prolonged cold, a process called vernalization, involves downregulation of the protein FLC, which would otherwise prevent flowering. This lowered FLC expression is maintained through subsequent development by the activity of VERNALIZATION (VRN) genes. VRN1 encodes a DNA-binding protein whereas VRN2 encodes a homologue of one of the Polycomb group proteins, which maintain the silencing of genes during animal development. Here we show that vernalization causes changes in histone methylation in discrete domains within the FLC locus, increasing dimethylation of lysines 9 and 27 on histone H3. Such modifications identify silenced chromatin states in Drosophila and human cells. Dimethylation of H3 K27 was lost only in vrn2 mutants, but dimethylation of H3 K9 was absent from both vrn1 and vrn2, consistent with VRN1 functioning downstream of VRN2. The epigenetic memory of winter is thus mediated by a 'histone code' that specifies a silent chromatin state conserved between animals and plants.     

Genome sequence of Silicibacter pomeroyi reveals adaptations to the marine environment

Since the recognition of prokaryotes as essential components of the oceanic food web, bacterioplankton have been acknowledged as catalysts of most major biogeochemical processes in the sea. Studying heterotrophic bacterioplankton has been challenging, however, as most major clades have never been cultured or have only been grown to low densities in sea water. Here we describe the genome sequence of Silicibacter pomeroyi, a member of the marine Roseobacter clade (Fig. 1), the relatives of which comprise approximately 10-20% of coastal and oceanic mixed-layer bacterioplankton. This first genome sequence from any major heterotrophic clade consists of a chromosome (4,109,442 base pairs) and megaplasmid (491,611 base pairs). Genome analysis indicates that this organism relies upon a lithoheterotrophic strategy that uses inorganic compounds (carbon monoxide and sulphide) to supplement heterotrophy. Silicibacter pomeroyi also has genes advantageous for associations with plankton and suspended particles, including genes for uptake of algal-derived compounds, use of metabolites from reducing microzones, rapid growth and cell-density-dependent regulation. This bacterium has a physiology distinct from that of marine oligotrophs, adding a new strategy to the recognized repertoire for coping with a nutrient-poor ocean.     

Similar meltwater contributions to glacial sea level changes from Antarctic and northern ice sheets

The period between 75,000 and 20,000 years ago was characterized by high variability in climate and sea level. Southern Ocean records of ice-rafted debris suggest a significant contribution to the sea level changes from melt water of Antarctic origin, in addition to likely contributions from northern ice sheets, but the relative volumes of melt water from northern and southern sources have yet to be established. Here we simulate the first-order impact of a range of relative meltwater releases from the two polar regions on the distribution of marine oxygen isotopes, using an intermediate complexity model. By comparing our simulations with oxygen isotope data from sediment cores, we infer that the contributions from Antarctica and the northern ice sheets to the documented sea level rises between 65,000 and 35,000 years ago were approximately equal, each accounting for a rise of about 15 m. The reductions in Antarctic ice volume implied by our analysis are comparable to that inferred previously for the Antarctic contribution to meltwater pulse 1A (refs 16, 17), which occurred about 14,200 years ago, during the last deglaciation.     

Ras regulates assembly of mitogenic signalling complexes through the effector protein IMP

The signal transduction cascade comprising Raf, mitogen-activated protein (MAP) kinase kinase (MEK) and MAP kinase is a Ras effector pathway that mediates diverse cellular responses to environmental cues and contributes to Ras-dependent oncogenic transformation. Here we report that the Ras effector protein Impedes Mitogenic signal Propagation (IMP) modulates sensitivity of the MAP kinase cascade to stimulus-dependent activation by limiting functional assembly of the core enzymatic components through the inactivation of KSR, a scaffold/adaptor protein that couples activated Raf to its substrate MEK. IMP is a Ras-responsive E3 ubiquitin ligase that, on activation of Ras, is modified by auto-polyubiquitination, which releases the inhibition of Raf-MEK complex formation. Thus, Ras activates the MAP kinase cascade through simultaneous dual effector interactions: induction of Raf kinase activity and derepression of Raf-MEK complex formation. IMP depletion results in increased stimulus-dependent MEK activation without alterations in the timing or duration of the response. These observations suggest that IMP functions as a threshold modulator, controlling sensitivity of the cascade to stimulus and providing a mechanism to allow adaptive behaviour of the cascade in chronic or complex signalling environments.     

A correlation between the cosmic microwave background and large-scale structure in the Universe

Observations of distant supernovae and the fluctuations in the cosmic microwave background (CMB) indicate that the expansion of the Universe may be accelerating under the action of a 'cosmological constant' or some other form of 'dark energy'. This dark energy now appears to dominate the Universe and not only alters its expansion rate, but also affects the evolution of fluctuations in the density of matter, slowing down the gravitational collapse of material (into, for example, clusters of galaxies) in recent times. Additional fluctuations in the temperature of CMB photons are induced as they pass through large-scale structures and these fluctuations are necessarily correlated with the distribution of relatively nearby matter. Here we report the detection of correlations between recent CMB data and two probes of large-scale structure: the X-ray background and the distribution of radio galaxies. These correlations are consistent with those predicted by dark energy, indicating that we are seeing the imprint of dark energy on the growth of structure in the Universe.     

Designing materials for biology and medicine

Biomaterials have played an enormous role in the success of medical devices and drug delivery systems. We discuss here new challenges and directions in biomaterials research. These include synthetic replacements for biological tissues, designing materials for specific medical applications, and materials for new applications such as diagnostics and array technologies.