Comprehensive analysis of the chromatin landscape in Drosophila melanogaster

Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which have an impact on cell differentiation, gene regulation and other key cellular processes. Here we present a genome-wide chromatin landscape for Drosophila melanogaster based on eighteen histone modifications, summarized by nine prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNase I hypersensitivity, GRO-Seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function.     

CENP-B preserves genome integrity at replication forks paused by retrotransposon LTR

Centromere-binding protein B (CENP-B) is a widely conserved DNA binding factor associated with heterochromatin and centromeric satellite repeats. In fission yeast, CENP-B homologues have been shown to silence long terminal repeat (LTR) retrotransposons by recruiting histone deacetylases. However, CENP-B factors also have unexplained roles in DNA replication. Here we show that a molecular function of CENP-B is to promote replication-fork progression through the LTR. Mutants have increased genomic instability caused by replication-fork blockage that depends on the DNA binding factor switch-activating protein 1 (Sap1), which is directly recruited by the LTR. The loss of Sap1-dependent barrier activity allows the unhindered progression of the replication fork, but results in rearrangements deleterious to the retrotransposon. We conclude that retrotransposons influence replication polarity through recruitment of Sap1 and transposition near replication-fork blocks, whereas CENP-B counteracts this activity and promotes fork stability. Our results may account for the role of LTR in fragile sites, and for the association of CENP-B with pericentromeric heterochromatin and tandem satellite repeats.     

Quantum gates and memory using microwave-dressed states

Trapped atomic ions have been used successfully to demonstrate basic elements of universal quantum information processing. Nevertheless, scaling up such methods to achieve large-scale, universal quantum information processing (or more specialized quantum simulations) remains challenging. The use of easily controllable and stable microwave sources, rather than complex laser systems, could remove obstacles to scalability. However, the microwave approach has drawbacks: it involves the use of magnetic-field-sensitive states, which shorten coherence times considerably, and requires large, stable magnetic field gradients. Here we show how to overcome both problems by using stationary atomic quantum states as qubits that are induced by microwave fields (that is, by dressing magnetic-field-sensitive states with microwave fields). This permits fast quantum logic, even in the presence of a small (effective) Lamb-Dicke parameter (and, therefore, moderate magnetic field gradients). We experimentally demonstrate the basic building blocks of this scheme, showing that the dressed states are long lived and that coherence times are increased by more than two orders of magnitude relative to those of bare magnetic-field-sensitive states. This improves the prospects of microwave-driven ion trap quantum information processing, and offers a route to extending coherence times in all systems that suffer from magnetic noise, such as neutral atoms, nitrogen-vacancy centres, quantum dots or circuit quantum electrodynamic systems.     

Microwave quantum logic gates for trapped ions

Control over physical systems at the quantum level is important in fields as diverse as metrology, information processing, simulation and chemistry. For trapped atomic ions, the quantized motional and internal degrees of freedom can be coherently manipulated with laser light. Similar control is difficult to achieve with radio-frequency or microwave radiation: the essential coupling between internal degrees of freedom and motion requires significant field changes over the extent of the atoms' motion, but such changes are negligible at these frequencies for freely propagating fields. An exception is in the near field of microwave currents in structures smaller than the free-space wavelength, where stronger gradients can be generated. Here we first manipulate coherently (on timescales of 20 nanoseconds) the internal quantum states of ions held in a microfabricated trap. The controlling magnetic fields are generated by microwave currents in electrodes that are integrated into the trap structure. We also generate entanglement between the internal degrees of freedom of two atoms with a gate operation suitable for general quantum computation; the entangled state has a fidelity of 0.76(3), where the uncertainty denotes standard error of the mean. Our approach, which involves integrating the quantum control mechanism into the trapping device in a scalable manner, could be applied to quantum information processing, simulation and spectroscopy.     

Detection of prokaryotic mRNA signifies microbial viability and promotes immunity

Live vaccines have long been known to trigger far more vigorous immune responses than their killed counterparts. This has been attributed to the ability of live microorganisms to replicate and express specialized virulence factors that facilitate invasion and infection of their hosts. However, protective immunization can often be achieved with a single injection of live, but not dead, attenuated microorganisms stripped of their virulence factors. Pathogen-associated molecular patterns (PAMPs), which are detected by the immune system, are present in both live and killed vaccines, indicating that certain poorly characterized aspects of live microorganisms, not incorporated in dead vaccines, are particularly effective at inducing protective immunity. Here we show that the mammalian innate immune system can directly sense microbial viability through detection of a special class of viability-associated PAMPs (vita-PAMPs). We identify prokaryotic messenger RNA as a vita-PAMP present only in viable bacteria, the recognition of which elicits a unique innate response and a robust adaptive antibody response. Notably, the innate response evoked by viability and prokaryotic mRNA was thus far considered to be reserved for pathogenic bacteria, but we show that even non-pathogenic bacteria in sterile tissues can trigger similar responses, provided that they are alive. Thus, the immune system actively gauges the infectious risk by searching PAMPs for signatures of microbial life and thus infectivity. Detection of vita-PAMPs triggers a state of alert not warranted for dead bacteria. Vaccine formulations that incorporate vita-PAMPs could thus combine the superior protection of live vaccines with the safety of dead vaccines.     

Heart regeneration

Heart failure plagues industrialized nations, killing more people than any other disease. It usually results from a deficiency of specialized cardiac muscle cells known as cardiomyocytes, and a robust therapy to regenerate lost myocardium could help millions of patients every year. Heart regeneration is well documented in amphibia and fish and in developing mammals. After birth, however, human heart regeneration becomes limited to very slow cardiomyocyte replacement. Several experimental strategies to remuscularize the injured heart using adult stem cells and pluripotent stem cells, cellular reprogramming and tissue engineering are in progress. Although many challenges remain, these interventions may eventually lead to better approaches to treat or prevent heart failure.     

Carbon loss from an unprecedented Arctic tundra wildfire

Arctic tundra soils store large amounts of carbon (C) in organic soil layers hundreds to thousands of years old that insulate, and in some cases maintain, permafrost soils. Fire has been largely absent from most of this biome since the early Holocene epoch, but its frequency and extent are increasing, probably in response to climate warming. The effect of fires on the C balance of tundra landscapes, however, remains largely unknown. The Anaktuvuk River fire in 2007 burned 1,039 square kilometres of Alaska's Arctic slope, making it the largest fire on record for the tundra biome and doubling the cumulative area burned since 1950 (ref. 5). Here we report that tundra ecosystems lost 2,016?±?435?g?C?m(-2) in the fire, an amount two orders of magnitude larger than annual net C exchange in undisturbed tundra. Sixty per cent of this C loss was from soil organic matter, and radiocarbon dating of residual soil layers revealed that the maximum age of soil C lost was 50 years. Scaled to the entire burned area, the fire released approximately 2.1?teragrams of C to the atmosphere, an amount similar in magnitude to the annual net C sink for the entire Arctic tundra biome averaged over the last quarter of the twentieth century. The magnitude of ecosystem C lost by fire, relative to both ecosystem and biome-scale fluxes, demonstrates that a climate-driven increase in tundra fire disturbance may represent a positive feedback, potentially offsetting Arctic greening and influencing the net C balance of the tundra biome.     

Molecular mechanism of anaerobic ammonium oxidation

Two distinct microbial processes, denitrification and anaerobic ammonium oxidation (anammox), are responsible for the release of fixed nitrogen as dinitrogen gas (N(2)) to the atmosphere. Denitrification has been studied for over 100 years and its intermediates and enzymes are well known. Even though anammox is a key biogeochemical process of equal importance, its molecular mechanism is unknown, but it was proposed to proceed through hydrazine (N(2)H(4)). Here we show that N(2)H(4) is produced from the anammox substrates ammonium and nitrite and that nitric oxide (NO) is the direct precursor of N(2)H(4). We resolved the genes and proteins central to anammox metabolism and purified the key enzymes that catalyse N(2)H(4) synthesis and its oxidation to N(2). These results present a new biochemical reaction forging an N-N bond and fill a lacuna in our understanding of the biochemical synthesis of the N(2) in the atmosphere. Furthermore, they reinforce the role of nitric oxide in the evolution of the nitrogen cycle.