@article{7210, abstract = {The rate of biological evolution depends on the fixation probability and on the fixation time of new mutants. Intensive research has focused on identifying population structures that augment the fixation probability of advantageous mutants. But these amplifiers of natural selection typically increase fixation time. Here we study population structures that achieve a tradeoff between fixation probability and time. First, we show that no amplifiers can have an asymptotically lower absorption time than the well-mixed population. Then we design population structures that substantially augment the fixation probability with just a minor increase in fixation time. Finally, we show that those structures enable higher effective rate of evolution than the well-mixed population provided that the rate of generating advantageous mutants is relatively low. Our work sheds light on how population structure affects the rate of evolution. Moreover, our structures could be useful for lab-based, medical, or industrial applications of evolutionary optimization.}, author = {Tkadlec, Josef and Pavlogiannis, Andreas and Chatterjee, Krishnendu and Nowak, Martin A.}, issn = {2399-3642}, journal = {Communications Biology}, publisher = {Springer Nature}, title = {{Population structure determines the tradeoff between fixation probability and fixation time}}, doi = {10.1038/s42003-019-0373-y}, volume = {2}, year = {2019}, } @article{7214, abstract = {Background: Many cancer genomes are extensively rearranged with highly aberrant chromosomal karyotypes. Structural and copy number variations in cancer genomes can be determined via abnormal mapping of sequenced reads to the reference genome. Recently it became possible to reconcile both of these types of large-scale variations into a karyotype graph representation of the rearranged cancer genomes. Such a representation, however, does not directly describe the linear and/or circular structure of the underlying rearranged cancer chromosomes, thus limiting possible analysis of cancer genomes somatic evolutionary process as well as functional genomic changes brought by the large-scale genome rearrangements. Results: Here we address the aforementioned limitation by introducing a novel methodological framework for recovering rearranged cancer chromosomes from karyotype graphs. For a cancer karyotype graph we formulate an Eulerian Decomposition Problem (EDP) of finding a collection of linear and/or circular rearranged cancer chromosomes that are determined by the graph. We derive and prove computational complexities for several variations of the EDP. We then demonstrate that Eulerian decomposition of the cancer karyotype graphs is not always unique and present the Consistent Contig Covering Problem (CCCP) of recovering unambiguous cancer contigs from the cancer karyotype graph, and describe a novel algorithm CCR capable of solving CCCP in polynomial time. We apply CCR on a prostate cancer dataset and demonstrate that it is capable of consistently recovering large cancer contigs even when underlying cancer genomes are highly rearranged. Conclusions: CCR can recover rearranged cancer contigs from karyotype graphs thereby addressing existing limitation in inferring chromosomal structures of rearranged cancer genomes and advancing our understanding of both patient/cancer-specific as well as the overall genetic instability in cancer.}, author = {Aganezov, Sergey and Zban, Ilya and Aksenov, Vitalii and Alexeev, Nikita and Schatz, Michael C.}, issn = {14712105}, journal = {BMC Bioinformatics}, publisher = {BMC}, title = {{Recovering rearranged cancer chromosomes from karyotype graphs}}, doi = {10.1186/s12859-019-3208-4}, volume = {20}, year = {2019}, } @inproceedings{7216, abstract = {We present LiveTraVeL (Live Transit Vehicle Labeling), a real-time system to label a stream of noisy observations of transit vehicle trajectories with the transit routes they are serving (e.g., northbound bus #5). In order to scale efficiently to large transit networks, our system first retrieves a small set of candidate routes from a geometrically indexed data structure, then applies a fine-grained scoring step to choose the best match. Given that real-time data remains unavailable for the majority of the world’s transit agencies, these inferences can help feed a real-time map of a transit system’s trips, infer transit trip delays in real time, or measure and correct noisy transit tracking data. This system can run on vehicle observations from a variety of sources that don’t attach route information to vehicle observations, such as public imagery streams or user-contributed transit vehicle sightings.We abstract away the specifics of the sensing system and demonstrate the effectiveness of our system on a "semisynthetic" dataset of all New York City buses, where we simulate sensed trajectories by starting with fully labeled vehicle trajectories reported via the GTFS-Realtime protocol, removing the transit route IDs, and perturbing locations with synthetic noise. Using just the geometric shapes of the trajectories, we demonstrate that our system converges on the correct route ID within a few minutes, even after a vehicle switches from serving one trip to the next.}, author = {Osang, Georg F and Cook, James and Fabrikant, Alex and Gruteser, Marco}, booktitle = {2019 IEEE Intelligent Transportation Systems Conference}, isbn = {9781538670248}, location = {Auckland, New Zealand}, publisher = {IEEE}, title = {{LiveTraVeL: Real-time matching of transit vehicle trajectories to transit routes at scale}}, doi = {10.1109/ITSC.2019.8917514}, year = {2019}, } @article{7225, abstract = {This is a literature teaching resource review for biologically inspired microfluidics courses or exploring the diverse applications of microfluidics. The structure is around key papers and model organisms. While courses gradually change over time, a focus remains on understanding how microfluidics has developed as well as what it can and cannot do for researchers. As a primary starting point, we cover micro-fluid mechanics principles and microfabrication of devices. A variety of applications are discussed using model prokaryotic and eukaryotic organisms from the set of bacteria (Escherichia coli), trypanosomes (Trypanosoma brucei), yeast (Saccharomyces cerevisiae), slime molds (Physarum polycephalum), worms (Caenorhabditis elegans), flies (Drosophila melangoster), plants (Arabidopsis thaliana), and mouse immune cells (Mus musculus). Other engineering and biochemical methods discussed include biomimetics, organ on a chip, inkjet, droplet microfluidics, biotic games, and diagnostics. While we have not yet reached the end-all lab on a chip, microfluidics can still be used effectively for specific applications.}, author = {Merrin, Jack}, issn = {23065354}, journal = {Bioengineering}, number = {4}, publisher = {MDPI}, title = {{Frontiers in microfluidics, a teaching resource review}}, doi = {10.3390/bioengineering6040109}, volume = {6}, year = {2019}, } @article{7226, author = {Jaksic, Vojkan and Seiringer, Robert}, issn = {00222488}, journal = {Journal of Mathematical Physics}, number = {12}, publisher = {AIP Publishing}, title = {{Introduction to the Special Collection: International Congress on Mathematical Physics (ICMP) 2018}}, doi = {10.1063/1.5138135}, volume = {60}, year = {2019}, } @inproceedings{7228, abstract = {Traditional concurrent programming involves manipulating shared mutable state. Alternatives to this programming style are communicating sequential processes (CSP) and actor models, which share data via explicit communication. These models have been known for almost half a century, and have recently had started to gain significant traction among modern programming languages. The common abstraction for communication between several processes is the channel. Although channels are similar to producer-consumer data structures, they have different semantics and support additional operations, such as the select expression. Despite their growing popularity, most known implementations of channels use lock-based data structures and can be rather inefficient. In this paper, we present the first efficient lock-free algorithm for implementing a communication channel for CSP programming. We provide implementations and experimental results in the Kotlin and Go programming languages. Our new algorithm outperforms existing implementations on many workloads, while providing non-blocking progress guarantee. Our design can serve as an example of how to construct general communication data structures for CSP and actor models. }, author = {Koval, Nikita and Alistarh, Dan-Adrian and Elizarov, Roman}, booktitle = {25th Anniversary of Euro-Par}, isbn = {978-3-0302-9399-4}, issn = {1611-3349}, location = {Göttingen, Germany}, pages = {317--333}, publisher = {Springer Nature}, title = {{Scalable FIFO channels for programming via communicating sequential processes}}, doi = {10.1007/978-3-030-29400-7_23}, volume = {11725}, year = {2019}, } @inproceedings{7230, abstract = {Simple drawings of graphs are those in which each pair of edges share at most one point, either a common endpoint or a proper crossing. In this paper we study the problem of extending a simple drawing D(G) of a graph G by inserting a set of edges from the complement of G into D(G) such that the result is a simple drawing. In the context of rectilinear drawings, the problem is trivial. For pseudolinear drawings, the existence of such an extension follows from Levi’s enlargement lemma. In contrast, we prove that deciding if a given set of edges can be inserted into a simple drawing is NP-complete. Moreover, we show that the maximization version of the problem is APX-hard. We also present a polynomial-time algorithm for deciding whether one edge uv can be inserted into D(G) when {u,v} is a dominating set for the graph G.}, author = {Arroyo Guevara, Alan M and Derka, Martin and Parada, Irene}, booktitle = {27th International Symposium on Graph Drawing and Network Visualization}, isbn = {978-3-0303-5801-3}, issn = {1611-3349}, location = {Prague, Czech Republic}, pages = {230--243}, publisher = {Springer Nature}, title = {{Extending simple drawings}}, doi = {10.1007/978-3-030-35802-0_18}, volume = {11904}, year = {2019}, } @inproceedings{7231, abstract = {Piecewise Barrier Tubes (PBT) is a new technique for flowpipe overapproximation for nonlinear systems with polynomial dynamics, which leverages a combination of barrier certificates. PBT has advantages over traditional time-step based methods in dealing with those nonlinear dynamical systems in which there is a large difference in speed between trajectories, producing an overapproximation that is time independent. However, the existing approach for PBT is not efficient due to the application of interval methods for enclosure-box computation, and it can only deal with continuous dynamical systems without uncertainty. In this paper, we extend the approach with the ability to handle both continuous and hybrid dynamical systems with uncertainty that can reside in parameters and/or noise. We also improve the efficiency of the method significantly, by avoiding the use of interval-based methods for the enclosure-box computation without loosing soundness. We have developed a C++ prototype implementing the proposed approach and we evaluate it on several benchmarks. The experiments show that our approach is more efficient and precise than other methods in the literature.}, author = {Kong, Hui and Bartocci, Ezio and Jiang, Yu and Henzinger, Thomas A}, booktitle = {17th International Conference on Formal Modeling and Analysis of Timed Systems}, isbn = {978-3-0302-9661-2}, issn = {1611-3349}, location = {Amsterdam, The Netherlands}, pages = {123--141}, publisher = {Springer Nature}, title = {{Piecewise robust barrier tubes for nonlinear hybrid systems with uncertainty}}, doi = {10.1007/978-3-030-29662-9_8}, volume = {11750}, year = {2019}, } @inproceedings{7232, abstract = {We present Mixed-time Signal Temporal Logic (STL−MX), a specification formalism which extends STL by capturing the discrete/ continuous time duality found in many cyber-physical systems (CPS), as well as mixed-signal electronic designs. In STL−MX, properties of components with continuous dynamics are expressed in STL, while specifications of components with discrete dynamics are written in LTL. To combine the two layers, we evaluate formulas on two traces, discrete- and continuous-time, and introduce two interface operators that map signals, properties and their satisfaction signals across the two time domains. We show that STL-mx has the expressive power of STL supplemented with an implicit T-periodic clock signal. We develop and implement an algorithm for monitoring STL-mx formulas and illustrate the approach using a mixed-signal example. }, author = {Ferrere, Thomas and Maler, Oded and Nickovic, Dejan}, booktitle = {17th International Conference on Formal Modeling and Analysis of Timed Systems}, isbn = {978-3-0302-9661-2}, issn = {1611-3349}, location = {Amsterdam, The Netherlands}, pages = {59--75}, publisher = {Springer Nature}, title = {{Mixed-time signal temporal logic}}, doi = {10.1007/978-3-030-29662-9_4}, volume = {11750}, year = {2019}, } @inproceedings{7233, abstract = {We demonstrate electro-optic frequency comb generation using a doubly resonant system comprising a whispering gallery mode disk resonator made of lithium niobate mounted inside a three dimensional copper cavity. We observe 180 sidebands centred at 1550 nm.}, author = {Rueda Sanchez, Alfredo R and Sedlmeir, Florian and Leuchs, Gerd and Kumari, Madhuri and Schwefel, Harald G.L.}, booktitle = {Nonlinear Optics, OSA Technical Digest}, isbn = {9781557528209}, location = {Waikoloa Beach, Hawaii (HI), United States}, publisher = {Optica Publishing Group}, title = {{Resonant electro-optic frequency comb generation in lithium niobate disk resonator inside a microwave cavity}}, doi = {10.1364/NLO.2019.NM2A.5}, year = {2019}, } @article{73, abstract = {We consider the space of probability measures on a discrete set X, endowed with a dynamical optimal transport metric. Given two probability measures supported in a subset Y⊆X, it is natural to ask whether they can be connected by a constant speed geodesic with support in Y at all times. Our main result answers this question affirmatively, under a suitable geometric condition on Y introduced in this paper. The proof relies on an extension result for subsolutions to discrete Hamilton-Jacobi equations, which is of independent interest.}, author = {Erbar, Matthias and Maas, Jan and Wirth, Melchior}, issn = {09442669}, journal = {Calculus of Variations and Partial Differential Equations}, number = {1}, publisher = {Springer}, title = {{On the geometry of geodesics in discrete optimal transport}}, doi = {10.1007/s00526-018-1456-1}, volume = {58}, year = {2019}, } @article{7340, abstract = {Coupling of endoplasmic reticulum stress to dimerisation‑dependent activation of the UPR transducer IRE1 is incompletely understood. Whilst the luminal co-chaperone ERdj4 promotes a complex between the Hsp70 BiP and IRE1's stress-sensing luminal domain (IRE1LD) that favours the latter's monomeric inactive state and loss of ERdj4 de-represses IRE1, evidence linking these cellular and in vitro observations is presently lacking. We report that enforced loading of endogenous BiP onto endogenous IRE1α repressed UPR signalling in CHO cells and deletions in the IRE1α locus that de-repressed the UPR in cells, encode flexible regions of IRE1LD that mediated BiP‑induced monomerisation in vitro. Changes in the hydrogen exchange mass spectrometry profile of IRE1LD induced by ERdj4 and BiP confirmed monomerisation and were consistent with active destabilisation of the IRE1LD dimer. Together, these observations support a competition model whereby waning ER stress passively partitions ERdj4 and BiP to IRE1LD to initiate active repression of UPR signalling.}, author = {Amin-Wetzel, Niko Paresh and Neidhardt, Lisa and Yan, Yahui and Mayer, Matthias P. and Ron, David}, issn = {2050084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR}}, doi = {10.7554/eLife.50793}, volume = {8}, year = {2019}, } @article{7391, abstract = {Electron microscopy (EM) is a technology that enables visualization of single proteins at a nanometer resolution. However, current protein analysis by EM mainly relies on immunolabeling with gold-particle-conjugated antibodies, which is compromised by large size of antibody, precluding precise detection of protein location in biological samples. Here, we develop a specific chemical labeling method for EM detection of proteins at single-molecular level. Rational design of α-helical peptide tag and probe structure provided a complementary reaction pair that enabled specific cysteine conjugation of the tag. The developed chemical labeling with gold-nanoparticle-conjugated probe showed significantly higher labeling efficiency and detectability of high-density clusters of tag-fused G protein-coupled receptors in freeze-fracture replicas compared with immunogold labeling. Furthermore, in ultrathin sections, the spatial resolution of the chemical labeling was significantly higher than that of antibody-mediated labeling. These results demonstrate substantial advantages of the chemical labeling approach for single protein visualization by EM.}, author = {Tabata, Shigekazu and Jevtic, Marijo and Kurashige, Nobutaka and Fuchida, Hirokazu and Kido, Munetsugu and Tani, Kazushi and Zenmyo, Naoki and Uchinomiya, Shohei and Harada, Harumi and Itakura, Makoto and Hamachi, Itaru and Shigemoto, Ryuichi and Ojida, Akio}, issn = {2589-0042}, journal = {iScience}, number = {12}, pages = {256--268}, publisher = {Elsevier}, title = {{Electron microscopic detection of single membrane proteins by a specific chemical labeling}}, doi = {10.1016/j.isci.2019.11.025}, volume = {22}, year = {2019}, } @article{7393, abstract = {The study of parallel ecological divergence provides important clues to the operation of natural selection. Parallel divergence often occurs in heterogeneous environments with different kinds of environmental gradients in different locations, but the genomic basis underlying this process is unknown. We investigated the genomics of rapid parallel adaptation in the marine snail Littorina saxatilis in response to two independent environmental axes (crab-predation versus wave-action and low-shore versus high-shore). Using pooled whole-genome resequencing, we show that sharing of genomic regions of high differentiation between environments is generally low but increases at smaller spatial scales. We identify different shared genomic regions of divergence for each environmental axis and show that most of these regions overlap with candidate chromosomal inversions. Several inversion regions are divergent and polymorphic across many localities. We argue that chromosomal inversions could store shared variation that fuels rapid parallel adaptation to heterogeneous environments, possibly as balanced polymorphism shared by adaptive gene flow.}, author = {Morales, Hernán E. and Faria, Rui and Johannesson, Kerstin and Larsson, Tomas and Panova, Marina and Westram, Anja M and Butlin, Roger K.}, issn = {2375-2548}, journal = {Science Advances}, number = {12}, publisher = {AAAS}, title = {{Genomic architecture of parallel ecological divergence: Beyond a single environmental contrast}}, doi = {10.1126/sciadv.aav9963}, volume = {5}, year = {2019}, } @article{7394, author = {Benková, Eva and Dagdas, Yasin}, issn = {1369-5266}, journal = {Current Opinion in Plant Biology}, number = {12}, pages = {A1--A2}, publisher = {Elsevier}, title = {{Editorial overview: Cell biology in the era of omics?}}, doi = {10.1016/j.pbi.2019.11.002}, volume = {52}, year = {2019}, } @article{7395, abstract = {The mitochondrial electron transport chain complexes are organized into supercomplexes (SCs) of defined stoichiometry, which have been proposed to regulate electron flux via substrate channeling. We demonstrate that CoQ trapping in the isolated SC I+III2 limits complex (C)I turnover, arguing against channeling. The SC structure, resolved at up to 3.8 Å in four distinct states, suggests that CoQ oxidation may be rate limiting because of unequal access of CoQ to the active sites of CIII2. CI shows a transition between “closed” and “open” conformations, accompanied by the striking rotation of a key transmembrane helix. Furthermore, the state of CI affects the conformational flexibility within CIII2, demonstrating crosstalk between the enzymes. CoQ was identified at only three of the four binding sites in CIII2, suggesting that interaction with CI disrupts CIII2 symmetry in a functionally relevant manner. Together, these observations indicate a more nuanced functional role for the SCs.}, author = {Letts, James A and Fiedorczuk, Karol and Degliesposti, Gianluca and Skehel, Mark and Sazanov, Leonid A}, issn = {1097-2765}, journal = {Molecular Cell}, number = {6}, pages = {1131--1146.e6}, publisher = {Cell Press}, title = {{Structures of respiratory supercomplex I+III2 reveal functional and conformational crosstalk}}, doi = {10.1016/j.molcel.2019.07.022}, volume = {75}, year = {2019}, } @article{7396, abstract = {The angular momentum of molecules, or, equivalently, their rotation in three-dimensional space, is ideally suited for quantum control. Molecular angular momentum is naturally quantized, time evolution is governed by a well-known Hamiltonian with only a few accurately known parameters, and transitions between rotational levels can be driven by external fields from various parts of the electromagnetic spectrum. Control over the rotational motion can be exerted in one-, two-, and many-body scenarios, thereby allowing one to probe Anderson localization, target stereoselectivity of bimolecular reactions, or encode quantum information to name just a few examples. The corresponding approaches to quantum control are pursued within separate, and typically disjoint, subfields of physics, including ultrafast science, cold collisions, ultracold gases, quantum information science, and condensed-matter physics. It is the purpose of this review to present the various control phenomena, which all rely on the same underlying physics, within a unified framework. To this end, recall the Hamiltonian for free rotations, assuming the rigid rotor approximation to be valid, and summarize the different ways for a rotor to interact with external electromagnetic fields. These interactions can be exploited for control—from achieving alignment, orientation, or laser cooling in a one-body framework, steering bimolecular collisions, or realizing a quantum computer or quantum simulator in the many-body setting.}, author = {Koch, Christiane P. and Lemeshko, Mikhail and Sugny, Dominique}, issn = {1539-0756}, journal = {Reviews of Modern Physics}, number = {3}, publisher = {American Physical Society}, title = {{Quantum control of molecular rotation}}, doi = {10.1103/revmodphys.91.035005}, volume = {91}, year = {2019}, } @article{7397, abstract = {Polymer additives can substantially reduce the drag of turbulent flows and the upperlimit, the so called “maximum drag reduction” (MDR) asymptote is universal, i.e. inde-pendent of the type of polymer and solvent used. Until recently, the consensus was that,in this limit, flows are in a marginal state where only a minimal level of turbulence activ-ity persists. Observations in direct numerical simulations using minimal sized channelsappeared to support this view and reported long “hibernation” periods where turbu-lence is marginalized. In simulations of pipe flow we find that, indeed, with increasingWeissenberg number (Wi), turbulence expresses long periods of hibernation if the domainsize is small. However, with increasing pipe length, the temporal hibernation continuouslyalters to spatio-temporal intermittency and here the flow consists of turbulent puffs sur-rounded by laminar flow. Moreover, upon an increase in Wi, the flow fully relaminarises,in agreement with recent experiments. At even larger Wi, a different instability is en-countered causing a drag increase towards MDR. Our findings hence link earlier minimalflow unit simulations with recent experiments and confirm that the addition of polymersinitially suppresses Newtonian turbulence and leads to a reverse transition. The MDRstate on the other hand results from a separate instability and the underlying dynamicscorresponds to the recently proposed state of elasto-inertial-turbulence (EIT).}, author = {Lopez Alonso, Jose M and Choueiri, George H and Hof, Björn}, issn = {1469-7645}, journal = {Journal of Fluid Mechanics}, pages = {699--719}, publisher = {CUP}, title = {{Dynamics of viscoelastic pipe flow at low Reynolds numbers in the maximum drag reduction limit}}, doi = {10.1017/jfm.2019.486}, volume = {874}, year = {2019}, } @article{7398, abstract = {Transporters of the solute carrier 6 (SLC6) family translocate their cognate substrate together with Na+ and Cl−. Detailed kinetic models exist for the transporters of GABA (GAT1/SLC6A1) and the monoamines dopamine (DAT/SLC6A3) and serotonin (SERT/SLC6A4). Here, we posited that the transport cycle of individual SLC6 transporters reflects the physiological requirements they operate under. We tested this hypothesis by analyzing the transport cycle of glycine transporter 1 (GlyT1/SLC6A9) and glycine transporter 2 (GlyT2/SLC6A5). GlyT2 is the only SLC6 family member known to translocate glycine, Na+, and Cl− in a 1:3:1 stoichiometry. We analyzed partial reactions in real time by electrophysiological recordings. Contrary to monoamine transporters, both GlyTs were found to have a high transport capacity driven by rapid return of the empty transporter after release of Cl− on the intracellular side. Rapid cycling of both GlyTs was further supported by highly cooperative binding of cosubstrate ions and substrate such that their forward transport mode was maintained even under conditions of elevated intracellular Na+ or Cl−. The most important differences in the transport cycle of GlyT1 and GlyT2 arose from the kinetics of charge movement and the resulting voltage-dependent rate-limiting reactions: the kinetics of GlyT1 were governed by transition of the substrate-bound transporter from outward- to inward-facing conformations, whereas the kinetics of GlyT2 were governed by Na+ binding (or a related conformational change). Kinetic modeling showed that the kinetics of GlyT1 are ideally suited for supplying the extracellular glycine levels required for NMDA receptor activation.}, author = {Erdem, Fatma Asli and Ilic, Marija and Koppensteiner, Peter and Gołacki, Jakub and Lubec, Gert and Freissmuth, Michael and Sandtner, Walter}, issn = {1540-7748}, journal = {The Journal of General Physiology}, number = {8}, pages = {1035--1050}, publisher = {Rockefeller University Press}, title = {{A comparison of the transport kinetics of glycine transporter 1 and glycine transporter 2}}, doi = {10.1085/jgp.201912318}, volume = {151}, year = {2019}, } @article{7399, abstract = {Long non-coding (lnc) RNAs are numerous and found throughout the mammalian genome, and many are thought to be involved in the regulation of gene expression. However, the majority remain relatively uncharacterised and of uncertain function making the use of model systems to uncover their mode of action valuable. Imprinted lncRNAs target and recruit epigenetic silencing factors to a cluster of imprinted genes on the same chromosome, making them one of the best characterized lncRNAs for silencing distant genes in cis. In this study we examined silencing of the distant imprinted gene Slc22a3 by the lncRNA Airn in the Igf2r imprinted cluster in mouse. Previously we proposed that imprinted lncRNAs may silence distant imprinted genes by disrupting promoter-enhancer interactions by being transcribed through the enhancer, which we called the enhancer interference hypothesis. Here we tested this hypothesis by first using allele-specific chromosome conformation capture (3C) to detect interactions between the Slc22a3 promoter and the locus of the Airn lncRNA that silences it on the paternal chromosome. In agreement with the model, we found interactions enriched on the maternal allele across the entire Airn gene consistent with multiple enhancer-promoter interactions. Therefore, to test the enhancer interference hypothesis we devised an approach to delete the entire Airn gene. However, the deletion showed that there are no essential enhancers for Slc22a2, Pde10a and Slc22a3 within the Airn gene, strongly indicating that the Airn RNA rather than its transcription is responsible for silencing distant imprinted genes. Furthermore, we found that silent imprinted genes were covered with large blocks of H3K27me3 on the repressed paternal allele. Therefore we propose an alternative hypothesis whereby the chromosome interactions may initially guide the lncRNA to target imprinted promoters and recruit repressive chromatin, and that these interactions are lost once silencing is established.}, author = {Andergassen, Daniel and Muckenhuber, Markus and Bammer, Philipp C. and Kulinski, Tomasz M. and Theussl, Hans-Christian and Shimizu, Takahiko and Penninger, Josef M. and Pauler, Florian and Hudson, Quanah J.}, issn = {1553-7404}, journal = {PLoS Genetics}, number = {7}, publisher = {Public Library of Science}, title = {{The Airn lncRNA does not require any DNA elements within its locus to silence distant imprinted genes}}, doi = {10.1371/journal.pgen.1008268}, volume = {15}, year = {2019}, }