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Combinatorial genomics

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https://www.readbyqxmd.com/read/28073951/nod-factors-potentiate-auxin-signaling-for-transcriptional-regulation-and-lateral-root-formation-in-medicago-truncatula
#1
Violaine Herrbach, Ximena Chirinos, David Rengel, Kokoévi Agbevenou, Rémy Vincent, Stéphanie Pateyron, Stéphanie Huguet, Sandrine Balzergue, Asher Pasha, Nicholas Provart, Clare Gough, Sandra Bensmihen
Nodulation (Nod) factors (NFs) are symbiotic molecules produced by rhizobia that are essential for establishment of the rhizobium-legume endosymbiosis. Purified NFs can stimulate lateral root formation (LRF) in Medicago truncatula, but little is known about the molecular mechanisms involved. Using a combination of reporter constructs, pharmacological and genetic approaches, we show that NFs act on early steps of LRF in M. truncatula, independently of the ethylene signaling pathway and of the cytokinin receptor MtCRE1, but in interaction with auxin...
January 10, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28068459/does-pharmacogenomic-testing-improve-clinical-outcomes-for-major-depressive-disorder-a-systematic-review-of-clinical-trials-and-cost-effectiveness-studies
#2
Joshua D Rosenblat, Yena Lee, Roger S McIntyre
OBJECTIVE: Pharmacogenomic testing has become scalable and available to the general public. Pharmacogenomics has shown promise for predicting antidepressant response and tolerability in the treatment of major depressive disorder (MDD). In theory, pharmacogenomics can improve clinical outcomes by guiding antidepressant selection and dosing. The current systematic review examines the extant literature to determine the impact of pharmacogenomic testing on clinical outcomes in MDD and assesses its cost-effectiveness...
January 3, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/28060954/activation-of-the-mtor-pathway-by-oxaliplatin-in-the-treatment-of-colorectal-cancer-liver-metastasis
#3
Min Lu, Amelia S Zessin, Wayne Glover, David S Hsu
BACKGROUND: Standard of care treatment for colorectal cancer liver metastasis consists of a cytotoxic chemotherapy in combination with a targeted agent. Clinical trials have guided the use of these combinatory therapies, but it remains unclear what the optimal combinations of cytotoxic chemotherapy with a targeted agent are. METHODS: Using a genomic based approach, gene expression profiling was obtained from tumor samples of patient with colorectal cancer liver metastasis who received an oxaliplatin based therapy...
2017: PloS One
https://www.readbyqxmd.com/read/28056762/hic-bench-comprehensive-and-reproducible-hi-c-data-analysis-designed-for-parameter-exploration-and-benchmarking
#4
Charalampos Lazaris, Stephen Kelly, Panagiotis Ntziachristos, Iannis Aifantis, Aristotelis Tsirigos
BACKGROUND: Chromatin conformation capture techniques have evolved rapidly over the last few years and have provided new insights into genome organization at an unprecedented resolution. Analysis of Hi-C data is complex and computationally intensive involving multiple tasks and requiring robust quality assessment. This has led to the development of several tools and methods for processing Hi-C data. However, most of the existing tools do not cover all aspects of the analysis and only offer few quality assessment options...
January 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28053956/aberrant-dna-double-strand-break-repair-threads-in-breast-carcinoma-orchestrating-genomic-insult-survival
#5
REVIEW
Azad Kumar, Shruti Purohit, Nilesh Kumar Sharma
Breast carcinoma is a heterogeneous disease that has exhibited rapid resistance to treatment in the last decade. Depending genotype and phenotype of breast cancer, there are discernible differences in DNA repair protein responses including DNA double strand break repair. It is a fact that different molecular sub-types of breast carcinoma activate these dedicated protein pathways in a distinct manner. The DNA double-strand damage repair machinery is manipulated by breast carcinoma to selectively repair the damage or insults inflicted by the genotoxic effects of chemotherapy or radiation therapy...
December 2016: Journal of Cancer Prevention
https://www.readbyqxmd.com/read/28053348/glucocorticoid-receptor-control-of-transcription-precision-and-plasticity-via-allostery
#6
Emily R Weikum, Matthew T Knuesel, Eric A Ortlund, Keith R Yamamoto
The glucocorticoid receptor (GR) is a constitutively expressed transcriptional regulatory factor (TRF) that controls many distinct gene networks, each uniquely determined by particular cellular and physiological contexts. The precision of GR-mediated responses seems to depend on combinatorial, context-specific assembly of GR-nucleated transcription regulatory complexes at genomic response elements. In turn, evidence suggests that context-driven plasticity is conferred by the integration of multiple signals, each serving as an allosteric effector of GR conformation, a key determinant of regulatory complex composition and activity...
January 5, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28045556/generalized-hultman-numbers-and-cycle-structures-of-breakpoint-graphs
#7
Nikita Alexeev, Anna Pologova, Max A Alekseyev
Genome rearrangements can be modeled as k-breaks, which break a genome at k positions and glue the resulting fragments in a new order. In particular, reversals, translocations, fusions, and fissions are modeled as 2-breaks, and transpositions are modeled as 3-breaks. Although k-break rearrangements for [Formula: see text] have not been observed in evolution, they are used in cancer genomics to model chromothripsis, a catastrophic event of multiple breakages happening simultaneously in a genome. It is known that the k-break distance between two genomes (i...
January 3, 2017: Journal of Computational Biology: a Journal of Computational Molecular Cell Biology
https://www.readbyqxmd.com/read/28012137/vapros-a-database-integration-approach-for-protein-genome-information-retrieval
#8
Takashi Gojobori, Kazuho Ikeo, Yukie Katayama, Takeshi Kawabata, Akira R Kinjo, Kengo Kinoshita, Yeondae Kwon, Ohsuke Migita, Hisashi Mizutani, Masafumi Muraoka, Koji Nagata, Satoshi Omori, Hideaki Sugawara, Daichi Yamada, Kei Yura
Life science research now heavily relies on all sorts of databases for genome sequences, transcription, protein three-dimensional (3D) structures, protein-protein interactions, phenotypes and so forth. The knowledge accumulated by all the omics research is so vast that a computer-aided search of data is now a prerequisite for starting a new study. In addition, a combinatory search throughout these databases has a chance to extract new ideas and new hypotheses that can be examined by wet-lab experiments. By virtually integrating the related databases on the Internet, we have built a new web application that facilitates life science researchers for retrieving experts' knowledge stored in the databases and for building a new hypothesis of the research target...
December 23, 2016: Journal of Structural and Functional Genomics
https://www.readbyqxmd.com/read/28007948/genome-metabolite-associations-revealed-low-heritability-high-genetic-complexity-and-causal-relations-for-leaf-metabolites-in-winter-wheat-triticum-aestivum
#9
Andrea Matros, Guozheng Liu, Anja Hartmann, Yong Jiang, Yusheng Zhao, Huange Wang, Erhard Ebmeyer, Viktor Korzun, Ralf Schachschneider, Ebrahim Kazman, Johannes Schacht, Friedrich Longin, Jochen Christoph Reif, Hans-Peter Mock
We investigated associations between the metabolic phenotype, consisting of quantitative data of 76 metabolites from 135 contrasting winter wheat (Triticum aestivum) lines, and 17 372 single nucleotide polymorphism (SNP) markers. Metabolite profiles were generated from flag leaves of plants from three different environments, with average repeatabilities of 0.5-0.6. The average heritability of 0.25 was unaffected by the heading date. Correlations among metabolites reflected their functional grouping, highlighting the strict coordination of various routes of the citric acid cycle...
December 22, 2016: Journal of Experimental Botany
https://www.readbyqxmd.com/read/28007784/an-ensemble-of-regulatory-elements-controls-runx3-spatiotemporal-expression-in-subsets-of-dorsal-root-ganglia-proprioceptive-neurons
#10
Elena Appel, Sarit Weissmann, Yehuda Salzberg, Kira Orlovsky, Varda Negreanu, Michael Tsoory, Calanit Raanan, Ester Feldmesser, Yael Bernstein, Orit Wolstein, Ditsa Levanon, Yoram Groner
The Runx3 transcription factor is essential for development and diversification of the dorsal root ganglia (DRGs) TrkC sensory neurons. In Runx3-deficient mice, developing TrkC neurons fail to extend central and peripheral afferents, leading to cell death and disruption of the stretch reflex circuit, resulting in severe limb ataxia. Despite its central role, the mechanisms underlying the spatiotemporal expression specificities of Runx3 in TrkC neurons were largely unknown. Here we first defined the genomic transcription unit encompassing regulatory elements (REs) that mediate the tissue-specific expression of Runx3...
December 1, 2016: Genes & Development
https://www.readbyqxmd.com/read/28007606/compositional-and-functional-diversity-of-canonical-prc1-complexes-in-mammals
#11
REVIEW
Katelyn E Connelly, Emily C Dykhuizen
The compositional complexity of Polycomb Repressive Complex 1 (PRC1) increased dramatically during vertebrate evolution. What is considered the "canonical" PRC1 complex consists of four subunits originally identified as regulators of body segmentation in Drosophila. In mammals, each of these four canonical subunits consists of two to six paralogs that associate in a combinatorial manner to produce over a hundred possible distinct PRC1 complexes with unknown function. Genetic studies have begun to define the phenotypic roles for different PRC1 paralogs; however, relating these phenotypes to unique biochemical and transcriptional function for the different paralogs has been challenging...
December 20, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27996308/anticancer-activity-of-curcumin-and-its-analogues-preclinical-and-clinical-studies
#12
Alessandro Allegra, Vanessa Innao, Sabina Russo, Demetrio Gerace, Andrea Alonci, Caterina Musolino
Curcumin has been shown to have a wide variety of therapeutic effects, ranging from anti-inflammatory, chemopreventive, anti-proliferative, and anti-metastatic. This review provides an overview of the recent research conducted to overcome the problems with the bioavailability of curcumin, and of the preclinical and clinical studies that have reported success in combinatorial strategies coupling curcumin with other treatments. Research on the signaling pathways that curcumin treatment targets shows that it potently acts on major intracellular components involved in key processes such as genomic modulations, cell invasion and cell death pathways...
December 20, 2016: Cancer Investigation
https://www.readbyqxmd.com/read/27993012/rational-design-of-small-molecules-targeting-oncogenic-noncoding-rnas-from-sequence
#13
Matthew D Disney, Alicia J Angelbello
The discovery of RNA catalysis in the 1980s and the dissemination of the human genome sequence at the start of this century inspired investigations of the regulatory roles of noncoding RNAs in biology. In fact, the Encyclopedia of DNA Elements (ENCODE) project has shown that only 1-2% of the human genome encodes protein, yet 75% is transcribed into RNA. Functional studies both preceding and following the ENCODE project have shown that these noncoding RNAs have important roles in regulating gene expression, developmental timing, and other critical functions...
December 20, 2016: Accounts of Chemical Research
https://www.readbyqxmd.com/read/27989935/the-multifaceted-roles-of-nuclear-factor-y-in-arabidopsis-thaliana-development-and-stress-responses
#14
Swadhin Swain, Zachary A Myers, Chamindika L Siriwardana, Ben F Holt
NUCLEAR FACTOR-Y (NF-Y) is a heterotrimeric transcription factor (TF) consisting of evolutionarily distinct NF-YA, NF-YB and NF-YC subunits. The functional NF-Y heterotrimer binds to CCAAT elements in eukaryotic gene promoters and influences their expression. The genome of the model organism Arabidopsis thaliana encodes 10 distinct NF-YA, NF-YB, and NF-YC proteins, allowing for enormous combinatorial and functional diversity. Two decades of research have elucidated the importance of NF-Ys in plant growth, development and stress responses; however, the molecular mechanisms of action remain largely unexplored...
October 28, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27984733/a-multiplexed-single-cell-crispr-screening-platform-enables-systematic-dissection-of-the-unfolded-protein-response
#15
Britt Adamson, Thomas M Norman, Marco Jost, Min Y Cho, James K Nuñez, Yuwen Chen, Jacqueline E Villalta, Luke A Gilbert, Max A Horlbeck, Marco Y Hein, Ryan A Pak, Andrew N Gray, Carol A Gross, Atray Dixit, Oren Parnas, Aviv Regev, Jonathan S Weissman
Functional genomics efforts face tradeoffs between number of perturbations examined and complexity of phenotypes measured. We bridge this gap with Perturb-seq, which combines droplet-based single-cell RNA-seq with a strategy for barcoding CRISPR-mediated perturbations, allowing many perturbations to be profiled in pooled format. We applied Perturb-seq to dissect the mammalian unfolded protein response (UPR) using single and combinatorial CRISPR perturbations. Two genome-scale CRISPR interference (CRISPRi) screens identified genes whose repression perturbs ER homeostasis...
December 15, 2016: Cell
https://www.readbyqxmd.com/read/27974206/distal-limb-patterning-requires-modulation-of-cis-regulatory-activities-by-hox13
#16
Rushikesh Sheth, Iros Barozzi, David Langlais, Marco Osterwalder, Stephen Nemec, Hanqian L Carlson, H Scott Stadler, Axel Visel, Jacques Drouin, Marie Kmita
The combinatorial expression of Hox genes along the body axes is a major determinant of cell fate and plays a pivotal role in generating the animal body plan. Loss of HOXA13 and HOXD13 transcription factors (HOX13) leads to digit agenesis in mice, but how HOX13 proteins regulate transcriptional outcomes and confer identity to the distal-most limb cells has remained elusive. Here, we report on the genome-wide profiling of HOXA13 and HOXD13 in vivo binding and changes of the transcriptome and chromatin state in the transition from the early to the late-distal limb developmental program, as well as in Hoxa13(-/-); Hoxd13(-/-) limbs...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27956602/pathway-swapping-toward-modular-engineering-of-essential-cellular-processes
#17
Niels G A Kuijpers, Daniel Solis-Escalante, Marijke A H Luttik, Markus M M Bisschops, Francine J Boonekamp, Marcel van den Broek, Jack T Pronk, Jean-Marc Daran, Pascale Daran-Lapujade
Recent developments in synthetic biology enable one-step implementation of entire metabolic pathways in industrial microorganisms. A similarly radical remodelling of central metabolism could greatly accelerate fundamental and applied research, but is impeded by the mosaic organization of microbial genomes. To eliminate this limitation, we propose and explore the concept of "pathway swapping," using yeast glycolysis as the experimental model. Construction of a "single-locus glycolysis" Saccharomyces cerevisiae platform enabled quick and easy replacement of this yeast's entire complement of 26 glycolytic isoenzymes by any alternative, functional glycolytic pathway configuration...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27936040/a-high-throughput-strategy-for-dissecting-mammalian-genetic-interactions
#18
Victoria B Stockman, Lila Ghamsari, Gorka Lasso, Barry Honig, Sagi D Shapira, Harris H Wang
Comprehensive delineation of complex cellular networks requires high-throughput interrogation of genetic interactions. To address this challenge, we describe the development of a multiplex combinatorial strategy to assess pairwise genetic interactions using CRISPR-Cas9 genome editing and next-generation sequencing. We characterize the performance of combinatorial genome editing and analysis using different promoter and gRNA designs and identified regions of the chimeric RNA that are compatible with next-generation sequencing preparation and quantification...
2016: PloS One
https://www.readbyqxmd.com/read/27924040/kdm2a-integrates-dna-and-histone-modification-signals-through-a-cxxc-phd-module-and-direct-interaction-with-hp1
#19
Julie Borgel, Marek Tyl, Karin Schiller, Zsofia Pusztai, Christopher M Dooley, Wen Deng, Carol Wooding, Richard J White, Tobias Warnecke, Heinrich Leonhardt, Elisabeth M Busch-Nentwich, Till Bartke
Functional genomic elements are marked by characteristic DNA and histone modification signatures. How combinatorial chromatin modification states are recognized by epigenetic reader proteins and how this is linked to their biological function is largely unknown. Here we provide a detailed molecular analysis of chromatin recognition by the lysine demethylase KDM2A. Using biochemical approaches we identify a nucleosome interaction module within KDM2A consisting of a CXXC type zinc finger, a PHD domain and a newly identified Heterochromatin Protein 1 (HP1) interaction motif that mediates direct binding between KDM2A and HP1...
October 24, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27921283/choices-have-consequences-the-nexus-between-dna-repair-pathways-and-genomic-instability-in-cancer
#20
REVIEW
Sonali Bhattacharjee, Saikat Nandi
BACKGROUND: The genome is under constant assault from a multitude of sources that can lead to the formation of DNA double-stand breaks (DSBs). DSBs are cytotoxic lesions, which if left unrepaired could lead to genomic instability, cancer and even cell death. However, erroneous repair of DSBs can lead to chromosomal rearrangements and loss of heterozygosity, which in turn can also cause cancer and cell death. Hence, although the repair of DSBs is crucial for the maintenance of genome integrity the process of repair need to be well regulated and closely monitored...
December 2016: Clinical and Translational Medicine
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