Nature Structural & Molecular Biology Contents: March 2013 Volume #20 pp 245 - 403

TABLE OF CONTENTS March 2013 Volume 20, Issue 3 Focus News and Views Editorial Reviews Research Highlights Articles Subscribe   Facebook   RSS   Recommend to library   Twitter   Advertisement New Nature Journals iPad app Read Nature anytime, anywhere. Subscribe to Nature on the iPad for only $35.99* Download the new app from the app store. *Apple exchange rates apply to international prices.   Focus Top Epigenetic Dynamics Focus issue: March 2013 Volume 20 No 3 Contents Editorial Reviews Research Highlights NPG Library Sponsor News and Views Top Host versus flu: antibodies win a round?   pp245 - 246 Christopher B Brooke and Jonathan W Yewdell doi:10.1038/nsmb.2524 Structural and functional analyses of three neutralizing antibodies against influenza virus H2 HA may explain why this HA subtype has disappeared from circulation in the human population and point to a potential new avenue for antiflu therapeutics. See also: Article by Xu et al. Breaking symmetry in SMCs   pp246 - 249 Amy L Upton and David J Sherratt doi:10.1038/nsmb.2525 SMC (structural maintenance of chromosomes) protein complexes act in chromosome processing in all domains of life. In this issue, a study of the prokaryotic SMC complex Smc-ScpAB reveals an unanticipated asymmetry despite Smc forming a symmetric homodimer. This asymmetry—contributed by two distinct binding sites in Smc for the kleisin ScpA—is crucial for function in vivo and bears similarities to the eukaryotic complexes formed by Smc heterodimers. See also: Article by Bürmann et al. DNA methylation: a matter of culture   pp249 - 251 Christoph Bock and Anton Wutz doi:10.1038/nsmb.2531 Pluripotent cells have been derived from the inner cell mass of mouse embryos and also from primordial germ cells. A new study shows that cell lines of both origins exhibit highly similar transcriptomes and surprisingly low DNA methylation levels when maintained in culture conditions that support naive pluripotency. These 2i conditions thus provide a closer approximation of in vivo development and new insights into the regulation of DNA methylation. See also: Article by Leitch et al. The helix turns at 60: writhing free in chromosomes   pp251 - 253 Richard R Sinden doi:10.1038/nsmb.2533 Dynamic supercoiling is a steady-state mechanical regulatory mechanism that influences DNA topology, transcription factor binding, gene expression, chromatin structure and long-range chromosome interactions. How genes and nongene regions are organized into supercoiled domains and remodeled by transcriptional activity in human cells has now been analyzed in two large-scale studies at the chromosome and genome levels, providing new insight into the organization and expression of genes within chromosomes. See also: Article by Naughton et al. | Article by Kouzine et al. Structural & Molecular Biology JOBS of the week Post-Doctoral Research Associate - Developmental Programming of Heart Disease (Fixed Term) University of Cambridge Postdoctoral Fellow University of Pittsburgh-Dept of Rheumatology & Clinical Immunology 16 open positions with Marie Curie mobility fellowships European School of Molecular Medicine (SEMM) Thesis Offer in structural biology Institut des Sciences Analytiques Imperial College London MRes in Biomedical Research Studentships Imperial College London - Faculty of Medicine More Science jobs from Structural & Molecular Biology EVENT 10th International Conference on Damage Assessment of Structures (DAMAS 2013) 08.-10.07.13 Dublin, Ireland More science events from Editorial Top Focus on Epigenetic Dynamics The dynamic epigenome   p258 doi:10.1038/nsmb.2534 The dynamic nature of functional information present in the genome—such as DNA methylation, histone modifications and chromatin organization—is beginning to be uncovered, along with the relationship between epigenomic patterning and developmental decisions or disease. Reviews Top Focus on Epigenetic Dynamics Regulation of nucleosome dynamics by histone modifications   pp259 - 266 Gabriel E Zentner and Steven Henikoff doi:10.1038/nsmb.2470 The properties of nucleosomes can be altered in various ways, including by covalent modification of histones. In this Review, the known properties of key histone modifications and the biological processes to which they are linked are examined to place the modifications in the context of nucleosome dynamics—that is, processes in which nucleosomes are translocated, unwrapped, evicted or replaced. Focus on Epigenetic Dynamics Determinants of nucleosome positioning   pp267 - 273 Kevin Struhl and Eran Segal doi:10.1038/nsmb.2506 Nucleosome positioning is crucial for gene expression and other DNA-related processes. In this Review, the authors consider mechanisms by which the genomic pattern of nucleosome positioning is achieved and conclude that nucleosome positioning is determined by the combined effects of several factors including DNA sequence, DNA-binding proteins, nucleosome remodelers and the transcription machinery. Focus on Epigenetic Dynamics DNA methylation dynamics in health and disease   pp274 - 281 Yehudit Bergman and Howard Cedar doi:10.1038/nsmb.2518 DNA methylation is an epigenetic mark that is erased in the early embryo and then re-established at the time of implantation. In this Review, dynamics of DNA methylation during normal development in vivo are discussed, starting from fertilization through embryogenesis and postnatal growth, as well as abnormal methylation changes that occur in cancer. Focus on Epigenetic Dynamics Epigenetic programming and reprogramming during development   pp282 - 289 Irene Cantone and Amanda G Fisher doi:10.1038/nsmb.2489 Global erasure and re-establishment of chromatin-based and DNA-based epigenetic marks occurs naturally in the mammalian life cycle, but it can also be artificially engineered using various reprogramming strategies. In this Review, recent advances in understanding how epigenetic remodeling contributes to cell-fate reprogramming in vivo and in vitro are summarized. Focus on Epigenetic Dynamics Functional implications of genome topology   pp290 - 299 Giacomo Cavalli and Tom Misteli doi:10.1038/nsmb.2474 A fundamental property of genomes is their topological organization in three-dimensional space in the cell nucleus. New imaging technologies and genome-wide biochemical approaches combined with functional data are starting to reveal the functional implications of genome topology, as discussed in this Review, and will enable a better understanding of how genome organization influences gene function, and vice versa. Focus on Epigenetic Dynamics Structure and function of long noncoding RNAs in epigenetic regulation   pp300 - 307 Tim R Mercer and John S Mattick doi:10.1038/nsmb.2480 Long noncoding RNAs (lncRNAs) fulfill a variety of regulatory roles in gene expression, which are dictated by their RNA structure, chemistry and modular domain structure. In this Review, the focus is on the well-characterized ability for lncRNAs to function as epigenetic modulators as part of a broad epigenetic regulatory network. Research Highlights Top Focus on Epigenetic Dynamics Window of opportunity | A lncRNA for the active X | STARR-seq enterprise | Directing DNA demethylation Articles Top Naive pluripotency is associated with global DNA hypomethylation   pp311 - 316 Harry G Leitch, Kirsten R McEwen, Aleksandra Turp, Vesela Encheva, Tom Carroll, Nils Grabole, William Mansfield, Buhe Nashun, Jaysen G Knezovich, Austin Smith, M Azim Surani and Petra Hajkova doi:10.1038/nsmb.2510 Naive pluripotent embryonic stem cells (ESCs) and embryonic germ cells (EGCs) have distinct developmental origins. Genome-wide expression and global DNA-methylation analyses now reveal that ESCs and ESGs are highly similar at the transcriptome level and, contrary to previous assumptions, are both characterized by DNA hypomethylation. Also, global methylation levels in both ESCs and EGCs are directly responsive to culture conditions. See also: News and Views by Bock & Wutz Acetylation limits 53BP1 association with damaged chromatin to promote homologous recombination   pp317 - 325 Jiangbo Tang, Nam Woo Cho, Gaofeng Cui, Erica M Manion, Niraj M Shanbhag, Maria Victoria Botuyan, Georges Mer and Roger A Greenberg doi:10.1038/nsmb.2499 Competitive binding of 53BP1 and BRCA1 determines DNA repair pathway choice at double-strand breaks. New work shows that acetylation of H4K16 by TIP60 tips the balance in favor of BRCA1 by limiting 53BP1 binding, thereby promoting repair through homologous recombination over nonhomologous end joining. Integration of the accelerator Aha1 in the Hsp90 co-chaperone cycle   pp326 - 331 Jing Li, Klaus Richter, Jochen Reinstein and Johannes Buchner doi:10.1038/nsmb.2502 The role of co-chaperone and Hsp90 activator Aha1 is now examined in conjunction with other co-chaperones in vivo and in vitro, to reveal how they regulate the progression of the Hsp90 cycle. Aha1 and Cpr6 interact with and activate Hsp90 in a synergistic manner and displace the inhibitory co-chaperone Sti1. Aha1 is eventually released from Hsp90 by p23. Chromatin signatures and retrotransposon profiling in mouse embryos reveal regulation of LINE-1 by RNA   pp332 - 338 Anas Fadloun, Stéphanie Le Gras, Bernard Jost, Céline Ziegler-Birling, Hazuki Takahashi, Eduardo Gorab, Piero Carninci and Maria-Elena Torres-Padilla doi:10.1038/nsmb.2495 Repetitive elements in differentiated cells are usually silenced. Genome-wide analyses in early mouse development show that repetitive-element expression decreases during development accompanied by the loss of active chromatin marks. LINE-1 and IAP retrotransposons become reactivated after fertilization, and LINE-1 transcription is regulated by short LINE-1 RNAs, which suggests that repetitive elements may be regulated through RNA during the earliest developmental stages. Trim24-repressed VL30 retrotransposons regulate gene expression by producing noncoding RNA   pp339 - 346 Benjamin Herquel, Khalid Ouararhni, Igor Martianov, Stéphanie Le Gras, Tao Ye, Céline Keime, Thierry Lerouge, Bernard Jost, Florence Cammas, Régine Losson and Irwin Davidson doi:10.1038/nsmb.2496 Trim24 and Trim33 are co-repressor complexes that suppress hepatocarcinogenesis. A new study now uncovers a function for Trim24 and Trim33 as repressors of VL30-type endogenous retroviruses in the liver. When derepressed, VL30 long terminal repeats (LTRs) function as promoter and enhancer elements deregulating expression of neighboring genes and generating noncoding enhancer RNAs that are required for LTR enhancer activity in hepatocytes. Human RECQ1 promotes restart of replication forks reversed by DNA topoisomerase I inhibition   pp347 - 354 Matteo Berti, Arnab Ray Chaudhuri, Saravanabhavan Thangavel, Shivasankari Gomathinayagam, Sasa Kenig, Marko Vujanovic, Federico Odreman, Timo Glatter, Simona Graziano, Ramiro Mendoza-Maldonado, Francesca Marino, Bojana Lucic, Valentina Biasin, Matthias Gstaiger, Ruedi Aebersold, Julia M Sidorova, Raymond J Monnat Jr, Massimo Lopes and Alessandro Vindigni doi:10.1038/nsmb.2501 The cytotoxic effects of topoisomerase I inhibitors such as camptothecin can be modulated by replication fork reversal, in a process that requires Poly(ADP-ribose) polymerase (PARP) activity. Here human RECQ1 helicase is shown to restore such regressed replication forks, whereas PARP1 activity restrains this RECQ1 function. Full-length Gαq–phospholipase C-β3 structure reveals interfaces of the C-terminal coiled-coil domain   pp355 - 362 Angeline M Lyon, Somnath Dutta, Cassandra A Boguth, Georgios Skiniotis and John J G Tesmer doi:10.1038/nsmb.2497 The regulatory importance of the C-terminal coiled-coil domain of PLCβ has long been known yet remains poorly understood. The crystal structure and cryo-EM reconstruction of full-length PLCβ3 bound to its activator Gαq reveals that the C terminus makes contact with both the catalytic core and Gαq to contribute to the complex regulation of the enzyme. A recurring motif for antibody recognition of the receptor-binding site of influenza hemagglutinin    pp363 - 370 Rui Xu, Jens C Krause, Ryan McBride, James C Paulson, James E Crowe Jr and Ian A Wilson doi:10.1038/nsmb.2500 Influenza virus hemagglutinin (HA) binds to sialic acid receptors on the host cell, but receptor analogs have failed as viral-entry inhibitors. Now crystal structures of H2 HA in complex with Fab fragments from three neutralizing antibodies reveal a new mode to target HA. All three antibodies use an aromatic residue to plug a conserved cavity in the HA-binding site for sialic acid. See also: News and Views by Brooke & Yewdell An asymmetric SMC–kleisin bridge in prokaryotic condensin   pp371 - 379 Frank Bürmann, Ho-Chul Shin, Jérôme Basquin, Young-Min Soh, Victor Giménez-Oya, Yeon-Gil Kim, Byung-Ha Oh and Stephan Gruber doi:10.1038/nsmb.2488 Prokaryotic condensins usually comprise an SMC homodimer, kleisin ScpA and ScpB. Structural and functional analyses of Bacillus subtilis condesin reveal an asymmetric bridge in which the termini of ScpA bind to distinct regions in each of the two SMC monomers. The findings suggest that the basic architecture for the tripartite condensin ring evolved before the emergence of eukaryotes. See also: News and Views by Upton & Sherratt Structural basis for duplex RNA recognition and cleavage by Archaeoglobus fulgidus C3PO   pp380 - 386 Eneida A Parizotto, Edward D Lowe and James S Parker doi:10.1038/nsmb.2487 Oligomeric Trax–Translin complexes, known as C3PO, are involved in RNA interference and tRNA processing in eukaryotic species including humans. Structural and functional analysis of a Trax-like protein from Archaeoglobus fulgidus that forms an octameric assembly resembling human C3PO provides insight into the mechanism of RNA recognition and cleavage. Transcription forms and remodels supercoiling domains unfolding large-scale chromatin structures   pp387 - 395 Catherine Naughton, Nicolaos Avlonitis, Samuel Corless, James G Prendergast, Ioulia K Mati, Paul P Eijk, Scott L Cockroft, Mark Bradley, Bauke Ylstra and Nick Gilbert doi:10.1038/nsmb.2509 A genome-wide mapping approach of DNA supercoiling in cells demonstrates that the genome is organized in supercoiling domains. Domains are formed and remodeled by transcription and topoisomerase activity and are flanked by GC-AT boundaries and CTCF binding sites. DNA supercoiling impacts on higher levels of chromatin organization and 'underwound' domains correlate with transcriptional activity. See also: News and Views by Sinden Transcription-dependent dynamic supercoiling is a short-range genomic force   pp396 - 403 Fedor Kouzine, Ashutosh Gupta, Laura Baranello, Damian Wojtowicz, Khadija Ben-Aissa, Juhong Liu, Teresa M Przytycka and David Levens doi:10.1038/nsmb.2517 The connection between dynamic DNA supercoiling and transcription is not well understood. High-resolution mapping of in vivo DNA supercoiling at transcription start sites (TSSs) now reveals that supercoils spread about 1.5 kb upstream of the TSSs of active genes. Highly expressed genes rely on topoisomerase II to dissipate dynamic supercoiling, whereas moderately expressed genes depend on topoisomerase I. See also: News and Views by Sinden Natureevents is a fully searchable, multi-disciplinary database designed to maximise exposure for events organisers. The contents of the Natureevents Directory are now live. The digital version is available here. 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