condensin驱动重构的X染色体剂量补偿拓扑中

The three-dimensional organization of a genome plays a critical role in regulating gene expression, yet little is known about the machinery and mechanisms that determine higher-order chromosome structure. Here we perform genome-wide chromosome conformation capture analysis, fluorescent in situ hybridization (FISH), and RNA-seq to obtain comprehensive three-dimensional (3D) maps of the Caenorhabditis elegans genome and to dissect X chromosome dosage compensation, which balances gene expression between XX hermaphrodites and XO males. The dosage compensation complex (DCC), a condensin complex, binds to both hermaphrodite X chromosomes via sequence-specific recruitment elements on X (rex sites) to reduce chromosome-wide gene expression by half. Most DCC condensin subunits also act in other condensin complexes to control the compaction and resolution of all mitotic and meiotic chromosomes. By comparing chromosome structure in wild-type and DCC-defective embryos, we show that the DCC remodels hermaphrodite X chromosomes into a sex-specific spatial conformation distinct from autosomes. Dosage-compensated X chromosomes consist of self-interacting domains (∼1 Mb) resembling mammalian topologically associating domains (TADs). TADs on X chromosomes have stronger boundaries and more regular spacing than on autosomes. Many TAD boundaries on X chromosomes coincide with the highest-affinity rex sites and become diminished or lost in DCC-defective mutants, thereby converting the topology of X to a conformation resembling autosomes. rex sites engage in DCC-dependent long-range interactions, with the most frequent interactions occurring between rex sites at DCC-dependent TAD boundaries. These results imply that the DCC reshapes the topology of X chromosomes by forming new TAD boundaries and reinforcing weak boundaries through interactions between its highest-affinity binding sites. As this model predicts, deletion of an endogenous rex site at a DCC-dependent TAD boundary using CRISPR/Cas9 greatly diminished the boundary. Thus, the DCC imposes a distinct higher-order structure onto X chromosomes while regulating gene expression chromosome-wide.

• http://feeds.nature.com/~r/nature/rss/aop/~3/4YjSKWJwFBA/nature14450

[详细]

人体基因组图谱揭示非经典的DNA甲基化变化

Understanding the diversity of human tissues is fundamental to disease and requires linking genetic information, which is identical in most of an individual’s cells, with epigenetic mechanisms that could have tissue-specific roles. Surveys of DNA methylation in human tissues have established a complex landscape including both tissue-specific and invariant methylation patterns. Here we report high coverage methylomes that catalogue cytosine methylation in all contexts for the major human organ systems, integrated with matched transcriptomes and genomic sequence. By combining these diverse data types with each individuals’ phased genome, we identified widespread tissue-specific differential CG methylation (mCG), partially methylated domains, allele-specific methylation and transcription, and the unexpected presence of non-CG methylation (mCH) in almost all human tissues. mCH correlated with tissue-specific functions, and using this mark, we made novel predictions of genes that escape X-chromosome inactivation in specific tissues. Overall, DNA methylation in several genomic contexts varies substantially among human tissues.

• http://feeds.nature.com/~r/nature/rss/aop/~3/Q2Dmhs370ww/nature14465

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在隐性突变TGF-β结合蛋白3（ltbp3）brachyolmia基因引起牙釉质发育不全

Inherited dental malformations constitute a clinically and genetically heterogeneous group of disorders. Here, we report on four families, three of them consanguineous, with an identical phenotype, characterized by significant short stature with brachyolmia and hypoplastic amelogenesis imperfecta (AI) with almost absent enamel. This phenotype was first described in 1996 by Verloes et al. as an autosomal recessive form of brachyolmia associated with AI. Whole-exome sequencing resulted in the identification of recessive hypomorphic mutations including deletion, nonsense and splice mutations, in the LTBP3 gene, which is involved in the TGF-beta signaling pathway. We further investigated gene expression during mouse development and tooth formation. Differentiated ameloblasts synthesizing enamel matrix proteins and odontoblasts expressed the gene. Study of an available knockout mouse model showed that the mutant mice displayed very thin to absent enamel in both incisors and molars, hereby recapitulating the AI phenotype in the human disorder.

• http://hmg.oxfordjournals.org/cgi/content/short/24/11/3038?rss=1

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多路复用的，位点特异性靶向RNA基因组显示长

CRISPR-Display is a modular and flexible platform that targets natural or synthetic noncoding RNA domains to specific genomic loci for functional studies and synthetic biology.

• http://feeds.nature.com/~r/nmeth/rss/aop/~3/g84sJO_Xcpg/nmeth.3433

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牵引显微镜鉴定次解析度粘连力调制

An analytical method, with accompanying software, is described for improved fidelity in traction force microscopy and is used to measure forces at emerging focal adhesions at high resolution.

• http://feeds.nature.com/~r/nmeth/rss/aop/~3/n9j0e8DcZZs/nmeth.3430

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布雷特监视GPCR配体结合的应用

Bioluminescence resonance energy transfer, from the substrate of a luciferase that is fused with a G protein–coupled receptor to a fluorescent dye covalently linked to a receptor ligand, allows the profiling of ligand affinity and binding kinetics.

• http://feeds.nature.com/~r/nmeth/rss/aop/~3/BBeldLnWvBE/nmeth.3398

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恶性疟原虫的遗传杂交在一个小鼠模型

A human-liver chimeric mouse supports the growth of recombinant Plasmodium falciparum progeny, enabling easy analysis of genetic crosses between parasite strains.

• http://feeds.nature.com/~r/nmeth/rss/aop/~3/6TppvR1EF9U/nmeth.3432

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结构生物学：复制病毒基因组

The structure of the La Crosse orthobunyavirus L protein suggests a new model for the replication of segmented negative-strand viral genomes.

• http://feeds.nature.com/~r/nrmicro/rss/current/~3/g4S7sdfAySo/nrmicro3507

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解码:一个集成的微分co-expression和微分表达式分析基因表达数据

Background: Both differential expression (DE) and differential co-expression (DC) analyses are appreciated as useful tools in understanding gene regulation related to complex diseases. The performance of integrating DE and DC, however, remains unexplored. Results: In this study, we proposed a novel analytical approach called DECODE ( D iffer e ntial Co -expression and D ifferential E xpression) to integrate DC and DE analyses of gene expression data. DECODE allows one to study the combined features of DC and DE of each transcript between two conditions. By incorporating information of the dependency between DC and DE variables, two optimal thresholds for defining substantial change in expression and co-expression are systematically defined for each gene based on chi-square maximization. By using these thresholds, genes can be categorized into four groups with either high or low DC and DE characteristics. In this study, DECODE was applied to a large breast cancer microarray data set consisted of two thousand tumor samples. By identifying genes with high DE and high DC, we demonstrated that DECODE could improve the detection of some functional gene sets such as those related to immune system, metastasis, lipid and glucose metabolism. Further investigation on the identified genes and the associated functional pathways would provide an additional level of understanding of complex disease mechanism. Conclusions: By complementing the recent DC and the traditional DE analyses, DECODE is a valuable methodology for investigating biological functions of genes exhibiting disease-associated DE and DC combined characteristics, which may not be easily revealed through DC or DE approach alone.DECODE is available at the Comprehensive R Archive Network (CRAN): http://cran.r-project.org/web/packages/decode/index.html.

• http://www.biomedcentral.com/1471-2105/16/182

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定量蛋白质组学分析的主机

Background: Acinetobacter baumannii is a major health problem. The most common infection caused by A. baumannii is hospital acquired pneumonia, and the associated mortality rate is approximately 50 %. Neither in vivo nor ex vivo expression profiling has been performed at the proteomic or transcriptomic level for pneumonia caused by A. baumannii. In this study, we characterized the proteome of A. baumannii under conditions that simulate those found in the airways, to gain some insight into how A. baumannii adapts to the host and to improve knowledge about the pathogenesis and virulence of this bacterium. A clinical strain of A. baumannii was grown under different conditions: in the presence of bronchoalveolar lavage fluid from infected rats, of RAW 264.7 cells to simulate conditions in the respiratory tract and in control conditions. We used iTRAQ labelling and LC-MALDI-TOF/TOF to investigate how A. baumannii responds on exposure to macrophages/BALF. Results: 179 proteins showed differential expression. In both models, proteins involved in the following processes were over-expressed: (i) pathogenesis and virulence (OmpA, YjjK); (ii) cell wall/membrane/envelope biogenesis (MurC); (iii) energy production and conversion (acetyl-CoA hydrolase); and (iv) translation (50S ribosomal protein L9). Proteins involved in the following were under-expressed: (i) lipid metabolism (short-chain dehydrogenase); (ii) amino acid metabolism and transport (aspartate aminotransferase); (iii) unknown function (DNA-binding protein); and (iv) inorganic ion transport and metabolism (hydroperoxidase). Conclusions: We observed alterations in cell wall synthesis and identified 2 upregulated virulence-associated proteins with >15 peptides/protein in both ex vivo models (OmpA and YjjK), suggesting that these proteins are fundamental for pathogenesis and virulence in the airways. This study is the first comprehensive overview of the ex vivo proteome of A. baumannii and is an important step towards identification of diagnostic biomarkers, novel drug targets and potential vaccine candidates in the fight against pneumonia caused by A. baumannii.

• http://www.biomedcentral.com/1471-2164/16/422

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智胜EF-Tu和核糖体：D型氨基酸翻译

Key components of the translational apparatus, i.e. ribosomes, elongation factor EF-Tu and most aminoacyl-tRNA synthetases, are stereoselective and prevent incorporation of d-amino acids (d-aa) into polypeptides. The rare appearance of d-aa in natural polypeptides arises from post-translational modifications or non-ribosomal synthesis. We introduce an in vitro translation system that enables single incorporation of 17 out of 18 tested d-aa into a polypeptide; incorporation of two or three successive d-aa was also observed in several cases. The system consists of wild-type components and d-aa are introduced via artificially charged, unmodified tRNA^Gly that was selected according to the rules of ‘thermodynamic compensation’. The results reveal an unexpected plasticity of the ribosomal peptidyltransferase center and thus shed new light on the mechanism of chiral discrimination during translation. Furthermore, ribosomal incorporation of d-aa into polypeptides may greatly expand the armamentarium of in vitro translation towards the identification of peptides and proteins with new properties and functions.

• http://nar.oxfordjournals.org/cgi/content/short/gkv566v1?rss=1

[详细]

控制保护在全基因组DNA甲基化的研究

Background: A commonplace analysis in high-throughput DNA methylation studies is the comparison of methylation extent between different functional regions, computed by averaging methylation states within region types and then comparing averages between regions. For example, it has been reported that methylation is more prevalent in coding regions as compared to their neighboring introns or UTRs, leading to hypotheses about novel forms of epigenetic regulation. Results: We have identified and characterized a bias present in these seemingly straightforward comparisons that results in the false detection of differences in methylation intensities across region types. This bias arises due to differences in conservation rates, rather than methylation rates, and is broadly present in the published literature. When controlling for conservation at coding start sites the differences in DNA methylation rates disappear. Moreover, a re-evaluation of methylation rates at intronexon junctions reveals that the magnitude of previously reported differences is greatly exaggerated. We introduce two correction methods to address this bias, an inferencebased matrix completion algorithm and an averaging approach, tailored to address different underlying biological questions. We evaluate how analysis using these corrections affects the detection of differences in DNA methylation across functional boundaries. Conclusions: We report here on a bias in DNA methylation comparative studies that originates in conservation rate differences and manifests itself in the false discovery of differences in DNA methylation intensities and their extents. We have characterized this bias and its broad implications, and show how to control for it so as to enable the study of a variety of biological questions.

• http://www.biomedcentral.com/1471-2164/16/420

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单核苷酸决议RNA-seq揭示新的监管机制的机会病原体<,>链球菌agalactiae < / >

Background: Streptococcus agalactiae, or Group B Streptococcus, is a leading cause of neonatal infections and an increasing cause of infections in adults with underlying diseases. In an effort to reconstruct the transcriptional networks involved in S. agalactiae physiology and pathogenesis, we performed an extensive and robust characterization of its transcriptome through a combination of differential RNA-sequencing in eight different growth conditions or genetic backgrounds and strand-specific RNA-sequencing. Results: Our study identified 1,210 transcription start sites (TSSs) and 655 transcript ends as well as 39 riboswitches and cis-regulatory regions, 39 cis-antisense non-coding RNAs and 47 small RNAs potentially acting in trans. Among these putative regulatory RNAs, ten were differentially expressed in response to an acid stress and two riboswitches sensed directly or indirectly the pH modification. Strikingly, 15% of the TSSs identified were associated with the incorporation of pseudo-templated nucleotides, showing that reiterative transcription is a pervasive process in S. agalactiae. In particular, 40% of the TSSs upstream genes involved in nucleotide metabolism show reiterative transcription potentially regulating gene expression, as exemplified for pyrG and thyA encoding the CTP synthase and the thymidylate synthase respectively. Conclusions: This comprehensive map of the transcriptome at the single nucleotide resolution led to the discovery of new regulatory mechanisms in S. agalactiae. It also provides the basis for in depth analyses of transcriptional networks in S. agalactiae and of the regulatory role of reiterative transcription following variations of intra-cellular nucleotide pools.

• http://www.biomedcentral.com/1471-2164/16/419

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Navigating the 3 d electron microscopy maps with EM - SURFER

Background: The Electron Microscopy DataBank (EMDB) is growing rapidly, accumulating biological structural data obtained mainly by electron microscopy and tomography, which are emerging techniques for determining large biomolecular complex and subcellular structures. Together with the Protein Data Bank (PDB), EMDB is becoming a fundamental resource of the tertiary structures of biological macromolecules. To take full advantage of this indispensable resource, the ability to search the database by structural similarity is essential. However, unlike high-resolution structures stored in PDB, methods for comparing low-resolution electron microscopy (EM) density maps in EMDB are not well established. Results: We developed a computational method for efficiently searching low-resolution EM maps. The method uses a compact fingerprint representation of EM maps based on the 3D Zernike descriptor, which is derived from a mathematical series expansion for EM maps that are considered as 3D functions. The method is implemented in a web server named EM-SURFER, which allows users to search against the entire EMDB in real-time. EM-SURFER compares the global shapes of EM maps. Examples of search results from different types of query structures are discussed. Conclusions: We developed EM-SURFER, which retrieves structurally relevant matches for query EM maps from EMDB within seconds. The unique capability of EM-SURFER to detect 3D shape similarity of low-resolution EM maps should prove invaluable in structural biology.

• http://www.biomedcentral.com/1471-2105/16/181

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DisVis:量化和可视化交互distance-restrained生物分子复合物的空间访问

Summary: We present DisVis, a Python package and command line tool to calculate the reduced accessible interaction space of distance-restrained binary protein complexes, allowing for direct visualization and quantification of the information content of the distance restraints. The approach is general and can also be used as a knowledge-based distance energy term in FFT-based docking directly during the sampling stage.

Availability and implementation: The source code with documentation is freely available from https://github.com/haddocking/disvis.

Contact: a.m.j.j.bonvin@uu.nl

Supplementary information: Available at Bioinformatics online.

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv333v1?rss=1

[详细]

RPdb: A database of experimentally verified cellular reprogramming records

Summary: Many cell lines can be reprogrammed to other cell lines by forced expression of a few transcription factors or by specifically designed culture methods, which have attracted a great interest in the field of regenerative medicine and stem cell research. Plenty of cell lines have been used to generate induced pluripotent stem cells (IPSCs) by expressing a group of genes and microRNAs. These IPSCs can differentiate into somatic cells to promote tissue regeneration. Similarly, many somatic cells can be directly reprogrammed to other cells without a stem cell state. All these findings are helpful in searching for new reprogramming methods and understanding the biological mechanism inside. However, to the best of our knowledge, there is still no database dedicated to integrating the reprogramming records. We built RPdb (cellular reprogramming database) to collect cellular reprogramming information and make it easy to access. All entries in RPdb are manually extracted from more than 2,000 published articles, which is helpful for researchers in regenerative medicine and cell biology.

Availability and Implementation: RPdb is freely available on the web at http://bioinformatics.ustc.edu.cn/rpdb with all major browsers supported.

Contact: aoli@ustc.edu.cn

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv331v1?rss=1

[详细]

lpNet:线性规划方法来重构信号转导网络

Summary: With the widespread availability of high-throughput experimental technologies it has become possible to study hundreds to thousands of cellular factors simultaneously, such as coding- or non-coding mRNA or protein concentrations. Still, extracting information about the underlying regulatory or signaling interactions from these data remains a difficult challenge. We present a flexible approach towards network inference based on linear programming. Our method reconstructs the interactions of factors from a combination of perturbation/non-perturbation and steady-state/time-series data. We show both on simulated and real data that our methods are able to reconstruct the underlying networks fast and efficiently, thus shedding new light on biological processes and, in particular, into disease’s mechanisms of action. We have implemented the approach as an R package available through bioconductor.

Availability and Implementation: This R package is freely available under the Gnu Public License (GPL-3) from bioconductor.org (http://bioconductor.org/packages/release/bioc/html/lpNet.html) and is compatible with most operating systems (Windows, Linux, Mac OS) and hardware architectures.

Contact: bettina.knapp@helmholtz-muenchen.de

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv327v1?rss=1

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“平加上”:最近WSxM实现生物研究

Summary: Scanning probe microscopy (SPM) is already a relevant tool in biological research at the nanoscale. We present ‘Flatten plus’, a recent and helpful implementation in the well-known WSxM free software package. ‘Flatten plus’ allows reducing low-frequency noise in SPM images in a semi-automated way preventing the appearance of typical artifacts associated with such filters.

Availability and implementation: WSxM is a free software implemented in C++ supported on MS Windows, but it can also be run under Mac or Linux using emulators such as Wine or Parallels. WSxM can be downloaded from http://www.wsxmsolutions.com/.

Contact: ignacio.horcas@wsxmsolutions.com

• http://bioinformatics.oxfordjournals.org/cgi/content/short/btv278v2?rss=1

[详细]

共变是分子进化的好方法

Recent developments in the analysis of amino acid covariation are leading to breakthroughs in protein structure prediction, protein design, and prediction of the interactome. It is assumed that observed patterns of covariation are caused by molecular coevolution, where substitutions at one site affect the evolutionary forces acting at neighboring sites. Our theoretical and empirical results cast doubt on this assumption. We demonstrate that the strongest coevolutionary signal is a decrease in evolutionary rate and that unfeasibly long times are required to produce coordinated substitutions. We find that covarying substitutions are mostly found on different branches of the phylogenetic tree, indicating that they are independent events that may or may not be attributable to coevolution. These observations undermine the hypothesis that molecular coevolution is the primary cause of the covariation signal. In contrast, we find that the pairs of residues with the strongest covariation signal tend to have low evolutionary rates, and that it is this low rate that gives rise to the covariation signal. Slowly evolving residue pairs are disproportionately located in the protein’s core, which explains covariation methods’ ability to detect pairs of residues that are close in three dimensions. These observations lead us to propose the "coevolution paradox": The strength of coevolution required to cause coordinated changes means the evolutionary rate is so low that such changes are highly unlikely to occur. As modern covariation methods may lead to breakthroughs in structural genomics, it is critical to recognize their biases and limitations.

• http://mbe.oxfordjournals.org/cgi/content/short/msv109v2?rss=1

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通过决策保持平衡

by Christoph W. Korn, Dominik R. Bach

Living organisms need to maintain energetic homeostasis. For many species, this implies taking actions with delayed consequences. For example, humans may have to decide between foraging for high-calorie but hard-to-get, and low-calorie but easy-to-get food, under threat of starvation. Homeostatic principles prescribe decisions that maximize the probability of sustaining appropriate energy levels across the entire foraging trajectory. Here, predictions from biological principles contrast with predictions from economic decision-making models based on maximizing the utility of the endpoint outcome of a choice. To empirically arbitrate between the predictions of biological and economic models for individual human decision-making, we devised a virtual foraging task in which players chose repeatedly between two foraging environments, lost energy by the passage of time, and gained energy probabilistically according to the statistics of the environment they chose. Reaching zero energy was framed as starvation. We used the mathematics of random walks to derive endpoint outcome distributions of the choices. This also furnished equivalent lotteries, presented in a purely economic, casino-like frame, in which starvation corresponded to winning nothing. Bayesian model comparison showed that—in both the foraging and the casino frames—participants’ choices depended jointly on the probability of starvation and the expected endpoint value of the outcome, but could not be explained by economic models based on combinations of statistical moments or on rank-dependent utility. This implies that under precisely defined constraints biological principles are better suited to explain human decision-making than economic models based on endpoint utility maximization.

• http://feeds.plos.org/~r/ploscompbiol/NewArticles/~3/r5XuREEWTn8/info%3Adoi%2F10.1371%2Fjournal.pcbi.1004301

[详细]

< smcaps > < / M smcaps > irinho:一、植物和动物和一般pre-miRNA先知for genomic sequencing数据和德普

Background: Several methods exist for the prediction of precursor miRNAs (pre-miRNAs) in genomic or sRNA-seq (small RNA sequences) data produced by NGS (Next Generation Sequencing). One key information used for this task is the characteristic hairpin structure adopted by pre-miRNAs, that in general are identified using RNA folders whose complexity is cubic in the size of the input. The vast majority of pre-miRNA predictors then rely on further information learned from previously validated miRNAs from the same or a closely related genome for the final prediction of new miRNAs. With this paper, we wished to address three main issues. The first was methodological and aimed at obtaining a more time-efficient predictor, however without losing in accuracy which represented a second issue. We indeed aimed at better predicting miRNAs at a genome scale, but also from sRNAseq data where in some cases, notably of plants, the current folding methods often infer the wrong structure. The third issue is related to the fact that it is important to rely as little as possible on previously recorded examples of miRNAs. We therefore also sought a method that is less dependent on previous miRNA records. Results: As concerns the first and second issues, we present a novel alternative to a classical folder based on a thermodynamic Nearest-Neighbour (NN) model for computing the free energy and predicting the classical hairpin structure of a pre-miRNA. We show that the free energies thus computed correlate well with those of RNAfold. This novel method, called Mirinho, has quadratic instead of cubic complexity and is much more efficient also in practice. When applied to sRNAseq data of plants, it gives in general better results than classical folders. On the third issue, we show that Mirinho, which uses as only knowledge the length of the loops and stem-arms and the free energy of the pre-miRNA hairpin, compares well with algorithms that require more information. The results, obtained with different datasets, are indeed similar to those of other approaches with which such a comparison was possible. These needed to be publicly available softwares that could be used on a large input. In some cases, Mirinho is even better in terms of sensitivity or precision. Conclusion: We provide a simpler and much faster method with very reasonable sensitivity and precision, which can be applied without special adaptation to the prediction of both animal and plant pre-miRNAs, using as input either genomic sequences or sRNA-seq data.

• http://www.biomedcentral.com/1471-2105/16/179

[详细]

在维甲酸诱导的转录，在ES细胞中的[资源]小鼠Hox基因簇的表观遗传谱的动态变化分析

The clustered Hox genes, which are highly conserved across metazoans, encode homeodomain-containing transcription factors that provide blueprint for segmental identity along the body axis. Recent studies have underscored that in addition to encoding Hox genes, the homeotic clusters contain key non-coding RNA genes that play central role in development. In this study, we have taken advantage of genome-wide approaches to provide a detailed analysis of retinoic acid (RA) induced transcriptional and epigenetic changes within the homeotic clusters of mouse embryonic stem cells. While there is a general collinear response, our analyses suggest a lack of strict colinearity for several genes in the HoxA and HoxB clusters. We have identified transcribed novel non-coding RNAs (ncRNAs) and their cis-regulatory elements that function in response to RA and demonstrated that the expression of these ncRNAs from both strands represent some of the most rapidly induced transcripts in ES cells. Finally, we have provided dynamic analyses of chromatin modifications for the coding and non-coding genes expressed upon activation and suggest that active transcription can occur in the presence of chromatin modifications and machineries associated with repressed transcription state over the clusters. Overall, our data provides a resource for a better understanding of the dynamic nature of the coding and non-coding transcripts and their associated chromatin marks in the regulation of homeotic gene transcription during development.

• http://genome.cshlp.org/cgi/reprint/gr.184978.114v1?rss=1

[详细]

DNA结合，调节基因的基因组特异性，通过故事和CRISPR /染色质重塑Cas9通过转录激活因子[研究]

Genome engineering technologies based on the CRISPR/Cas9 and TALE systems are enabling new approaches in science and biotechnology. However, the specificity of these tools in complex genomes and the role of chromatin structure in determining DNA-binding are not well understood. We analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators in human cells using ChIP-seq to assess DNA-binding specificity and RNA-seq to measure the specificity of perturbing the transcriptome. Additionally, DNase-seq was used to assess genome-wide chromatin remodeling that occurs as a result of their action. Our results show that these transcription factors are highly specific in both DNA-binding and gene regulation, and are able to open targeted regions of closed chromatin independent of gene activation. Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function.

• http://genome.cshlp.org/cgi/reprint/gr.179044.114v1?rss=1

[详细]

薄荷：软件识别序列和核酸的轨迹短程相互作用

Structural biology experiments and structure prediction tools have provided many high-resolution three-dimensional structures of nucleic acids. Also, molecular dynamics force field parameters have been adapted to simulating charged and flexible nucleic acid structures on microsecond time scales. Therefore, we can generate the dynamics of DNA or RNA molecules, but we still lack adequate tools for the analysis of the resulting huge amounts of data. We present MINT (Motif Identifier for Nucleic acids Trajectory) — an automatic tool for analyzing three-dimensional structures of RNA and DNA, and their full-atom molecular dynamics trajectories or other conformation sets (e.g. X-ray or nuclear magnetic resonance-derived structures). For each RNA or DNA conformation MINT determines the hydrogen bonding network resolving the base pairing patterns, identifies secondary structure motifs (helices, junctions, loops, etc.) and pseudoknots. MINT also estimates the energy of stacking and phosphate anion-base interactions. For many conformations, as in a molecular dynamics trajectory, MINT provides averages of the above structural and energetic features and their evolution. We show MINT functionality based on all-atom explicit solvent molecular dynamics trajectory of the 30S ribosomal subunit.

• http://nar.oxfordjournals.org/cgi/content/short/gkv559v1?rss=1

[详细]