p53-binding protein 1 (53BP1) is known to be an important mediator of the DNA-damage response1, with di-methylation of histone H4 lysine 20 (H4K20me2) critical to the recruitment of 53BP1 to double strand breaks (DSBs)2,3. However, it is not clear how 53BP1 is specifically targeted to the sites of DNA damage, since the overall level of H4K20me2 does not seem to increase following DNA damage. It has been proposed that DNA breaks may cause exposure of methylated H4K20 previously buried within the chromosome, however experimental evidence for such a model is lacking. Here we found that H4K20 methylation actually increases locally upon the induction of DSBs and that methylation of H4K20 at DSBs is mediated by the histone methyltransferase (HMT) MMSET (also known as NSD2 or WHSC1). Downregulation of MMSET significantly decreases H4K20 methylation at DSBs and the subsequent accumulation of 53BP1. We further found that the recruitment of MMSET to DSBs requires the γH2AX-MDC1 pathway, specifically the interaction between the MDC1 BRCT domain and phosphorylated Ser102 of MMSET. Thus, we propose that a pathway involving γH2AX-MDC1-MMSET regulates the induction of H4K20 methylation on histones around DSBs which, in turn, facilitates 53BP1 recruitment.

BackgroundThe concept of an equivalence group, a cluster of cells with equal potential to adopt the same specific fate, has served as a useful paradigm to understand neural cell type specification. In the Drosophila eye, a set of five cells, called the 'R7 equivalence group', generates a single photoreceptor neuron and four lens-secreting epithelial cells. This choice between neuronal versus non-neuronal cell fates rests on differential requirements for, and cross-talk between, Notch/Delta- and Ras/mitogen-activated protein kinase (MAPK)-dependent signaling pathways. However, many questions remain unanswered related to how downstream events of these two signaling pathways mediate distinct cell fate decisions.ResultsHere, we demonstrate that two direct downstream targets of Ras and Notch signaling, the transcription factors Prospero and dPax2, are essential regulators of neuronal versus non-neuronal cell fate decisions in the R7 equivalence group. Prospero controls high activated MAPK levels required for neuronal fate, whereas dPax2 represses Delta expression to prevent neuronal fate. Importantly, activity from both factors is required for proper cell fate decisions to occur.ConclusionsThese data demonstrate that Ras and Notch signaling are integrated during cell fate decisions within the R7 equivalence group through the combinatorial and opposing activities of Pros and dPax2. Our study provides one of the first examples of how the differential expression and synergistic roles of two independent transcription factors determine cell fate within an equivalence group. Since the integration of Ras and Notch signaling is associated with many developmental and cancer models, these findings should provide new insights into how cell specificity is achieved by ubiquitously used signaling pathways in diverse biological contexts.

Quantum repeaters -important components of a scalable quantum internet -enable the entanglement to be distributed over long distances. The standard paradigm for a quantum repeater relies on a necessary demanding requirement of quantum memory. Despite significant progress, the limited performance of quantum memory makes practical quantum repeaters still a great challenge. Remarkably, a proposed allphotonic quantum repeater avoids the need for quantum memory by harnessing the graph states in the repeater nodes. Here we perform an experimental demonstration of an all-photonic quantum repeater using linear optics. By manipulating a 12-photon interferometer, we implement a 2×2 parallel all-photonic quantum repeater, and observe an 89% enhancement of entanglement-generation rate over the standard parallel entanglement swapping. These results open a new way towards designing repeaters with efficient single-photon sources and photonic graph states, and suggest that the all-photonic scheme represents an alternative path -parallel to that of matter-memory-based schemes -towards realizing practical quantum repeaters.Recent years have seen enormous interest in quantum communication driven by its remarkable features of secure communication [1], quantum teleportation [2] and distributed quantum computing [3]. Photons are considered to be the optimal medium for quantum communication because of their flying nature and compatibility with current telecommunications networks. However the maximum communication distance is currently severely limited by photon loss in quantum channels, such as optical fibres. One viable solution is to use satellites as relays to transmit photons over a free-space channel [4,5]. In fibre-based telecommunications networks, quantum repeaters are believed to be the most promising way to overcome the distance limit [6]. The standard paradigm for a quantum repeater [7,8] consists of three basic technologies namely entanglement swapping [9, 10], entanglement purification [11,12] and quantum memory [13][14][15]. Recently, significant progress has been made both theoretically [16][17][18] and experimentally [19][20][21]. However, the limited performance of current quantum memories [22] remains a major obstacle in realizing practical quantum repeaters unless there is a future experimental breakthrough.

Distributed quantum metrology can enhance the sensitivity for sensing spatially distributed parameters beyond the classical limits. Here we demonstrate distributed quantum phase estimation with discrete variables to achieve Heisenberg limit phase measurements. Based on parallel entanglement in modes and particles, we demonstrate distributed quantum sensing for both individual phase shifts and an averaged phase shift, with an error reduction up to 1.4 dB and 2.7 dB below the shot-noise limit. Furthermore, we demonstrate a combined strategy with parallel mode entanglement and multiple passes of the phase shifter in each mode. In particular, our experiment uses six entangled photons with each photon passing the phase shifter up to six times, and achieves a total number of photon passes N = 21 at an error reduction up to 4.7 dB below the shot-noise limit. Our research provides a faithful 1