TRIM24 links a non-canonical histone signature to breast cancer

Recognition of modified histone species by distinct structural domains within 'reader' proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.     

Hydatellaceae are water lilies with gymnospermous tendencies

The flowering plant family Hydatellaceae was recently discovered to be allied to the ancient angiosperm lineage Nymphaeales (water lilies). Because of its critical phylogenetic position, members of the Hydatellaceae have the potential to provide insights into the origin and early diversification of angiosperms. Here I report that Hydatella expresses several rare embryological features that, in combination, are found only in members of the Nymphaeales. At maturity, the female gametophyte is four-celled, four-nucleate and will produce a diploid endosperm, as is characteristic of most early divergent angiosperm lineages. As with all members of the Nymphaeales, endosperm in Hydatella is minimally developed and perisperm is the major embryo-nourishing tissue within the seed. Remarkably, Hydatella exhibits a maternal seed-provisioning strategy that is unique among flowering plants, but common to all gymnosperms: pre-fertilization allocation of nutrients to the embryo-nourishing tissue. This exceptional case of pre-fertilization maternal provisioning of a seed in Hydatella may well be an apomorphic feature of Hydatellaceae alone but, given the newly discovered phylogenetic position of this family, potentially represents a plesiomorphic and transitional condition associated with the origin of flowering plants from gymnospermous ancestors.     

Semi-annual oscillations in Saturn's low-latitude stratospheric temperatures

Observations of oscillations of temperature and wind in planetary atmospheres provide a means of generalizing models for atmospheric dynamics in a diverse set of planets in the Solar System and elsewhere. An equatorial oscillation similar to one in the Earth's atmosphere has been discovered in Jupiter. Here we report the existence of similar oscillations in Saturn's atmosphere, from an analysis of over two decades of spatially resolved observations of its 7.8-microm methane and 12.2-microm ethane stratospheric emissions, where we compare zonal-mean stratospheric brightness temperatures at planetographic latitudes of 3.6 degrees and 15.5 degrees in both the northern and the southern hemispheres. These results support the interpretation of vertical and meridional variability of temperatures in Saturn's stratosphere as a manifestation of a wave phenomenon similar to that on the Earth and in Jupiter. The period of this oscillation is 14.8 +/- 1.2 terrestrial years, roughly half of Saturn's year, suggesting the influence of seasonal forcing, as is the case with the Earth's semi-annual oscillation.     

Preserving cell shape under environmental stress

Maintaining cell shape and tone is crucial for the function and survival of cells and tissues. Mechanotransduction relies on the transformation of minuscule mechanical forces into high-fidelity electrical responses. When mechanoreceptors are stimulated, mechanically sensitive cation channels open and produce an inward transduction current that depolarizes the cell. For this process to operate effectively, the transduction machinery has to retain integrity and remain unfailingly independent of environmental changes. This is particularly challenging for poikilothermic organisms, where changes in temperature in the environment may impact the function of mechanoreceptor neurons. Thus, we wondered how insects whose habitat might quickly vary over several tens of degrees of temperature manage to maintain highly effective mechanical senses. We screened for Drosophila mutants with defective mechanical responses at elevated ambient temperatures, and identified a gene, spam, whose role is to protect the mechanosensory organ from massive cellular deformation caused by heat-induced osmotic imbalance. Here we show that Spam protein forms an extracellular shield that guards mechanosensory neurons from environmental insult. Remarkably, heterologously expressed Spam protein also endowed other cells with superb defence against physically and chemically induced deformation. We studied the mechanical impact of Spam coating and show that spam-coated cells are up to ten times stiffer than uncoated controls. Together, these results help explain how poikilothermic organisms preserve the architecture of critical cells during environmental stress, and illustrate an elegant and simple solution to such challenge.     

Mitochondrial dysfunction and apoptosis in myopathic mice with collagen VI deficiency

Collagen VI is an extracellular matrix protein that forms a microfilamentous network in skeletal muscles and other organs. Inherited mutations in genes encoding collagen VI in humans cause two muscle diseases, Bethlem myopathy and Ullrich congenital muscular dystrophy. We previously generated collagen VI-deficient (Col6a1-/-) mice and showed that they have a muscle phenotype that strongly resembles Bethlem myopathy. The pathophysiological defects and mechanisms leading to the myopathic disorder were not known. Here we show that Col6a1-/- muscles have a loss of contractile strength associated with ultrastructural alterations of sarcoplasmic reticulum (SR) and mitochondria and spontaneous apoptosis. We found a latent mitochondrial dysfunction in myofibers of Col6a1-/- mice on incubation with the selective F1F(O)-ATPase inhibitor oligomycin, which caused mitochondrial depolarization, Ca2+ deregulation and increased apoptosis. These defects were reversible, as they could be normalized by plating Col6a1-/- myofibers on collagen VI or by addition of cyclosporin A (CsA), the inhibitor of mitochondrial permeability transition pore (PTP). Treatment of Col6a1-/- mice with CsA rescued the muscle ultrastructural defects and markedly decreased the number of apoptotic nuclei in vivo. These findings indicate that collagen VI myopathies have an unexpected mitochondrial pathogenesis that could be exploited for therapeutic intervention.     

Observation of rare-earth segregation in silicon nitride ceramics at subnanometre dimensions

Silicon nitride (Si3N4) ceramics are used in numerous applications because of their superior mechanical properties. Their intrinsically brittle nature is a critical issue, but can be overcome by introducing whisker-like microstructural features. However, the formation of such anisotropic grains is very sensitive to the type of cations used as the sintering additives. Understanding the origin of dopant effects, central to the design of high-performance Si3N4 ceramics, has been sought for many years. Here we show direct images of dopant atoms (La) within the nanometre-scale intergranular amorphous films typically found at grain boundaries, using aberration corrected Z-contrast scanning transmission electron microscopy. It is clearly shown that the La atoms preferentially segregate to the amorphous/crystal interfaces. First-principles calculations confirm the strong preference of La for the crystalline surfaces, which is essential for forming elongated grains and a toughened microstructure. Whereas principles of micrometre-scale structural design are currently used to improve the mechanical properties of ceramics, this work represents a step towards the atomic-level structural engineering required for the next generation of ceramics.