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https://www.readbyqxmd.com/read/29410437/unraveling-the-determinants-of-microrna-mediated-regulation-using-a-massively-parallel-reporter-assay
#1
Ilya Vainberg Slutskin, Shira Weingarten-Gabbay, Ronit Nir, Adina Weinberger, Eran Segal
Despite extensive research, the sequence features affecting microRNA-mediated regulation are not well understood, limiting our ability to predict gene expression levels in both native and synthetic sequences. Here we employed a massively parallel reporter assay to investigate the effect of over 14,000 rationally designed 3' UTR sequences on reporter construct repression. We found that multiple factors, including microRNA identity, hybridization energy, target accessibility, and target multiplicity, can be manipulated to achieve a predictable, up to 57-fold, change in protein repression...
February 6, 2018: Nature Communications
https://www.readbyqxmd.com/read/29223004/towards-utilization-of-the-human-genome-and-microbiome-for-personalized-nutrition
#2
REVIEW
Stavros Bashiardes, Anastasia Godneva, Eran Elinav, Eran Segal
Generalized dietary and lifestyle guidelines have been formulated and published for decades now from a variety of relevant agencies in an attempt to guide people towards healthy choices. As the pandemic rise in metabolic diseases continues to increase, it has become clear that the one-fit-for-all diet approach does not work and that there is a significant variation in inter-individual responses to diet and lifestyle interventions. Recent technological advances have given an unprecedented insight into the sources of this variation, pointing towards our genome and microbiome as potentially and previously under-explored culprits contributing to individually unique dietary responses...
December 6, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/29202942/microbiome-at-the-frontier-of-personalized-medicine
#3
REVIEW
Purna C Kashyap, Nicholas Chia, Heidi Nelson, Eran Segal, Eran Elinav
The genomic revolution promises to transform our approach to treat patients by individualizing treatments, reducing adverse events, and decreasing health care costs. The early advances using this have been realized primarily by optimizing preventive and therapeutic approaches in cancer using human genome sequencing. The ability to characterize the microbiome, which includes all the microbes that reside within and upon us and all their genetic elements, using next-generation sequencing allows us to now incorporate this important contributor to human disease into developing new preventive and therapeutic strategies...
December 2017: Mayo Clinic Proceedings
https://www.readbyqxmd.com/read/28922394/sequence-features-of-viral-and-human-internal-ribosome-entry-sites-predictive-of-their-activity
#4
Alexey A Gritsenko, Shira Weingarten-Gabbay, Shani Elias-Kirma, Ronit Nir, Dick de Ridder, Eran Segal
Translation of mRNAs through Internal Ribosome Entry Sites (IRESs) has emerged as a prominent mechanism of cellular and viral initiation. It supports cap-independent translation of select cellular genes under normal conditions, and in conditions when cap-dependent translation is inhibited. IRES structure and sequence are believed to be involved in this process. However due to the small number of IRESs known, there have been no systematic investigations of the determinants of IRES activity. With the recent discovery of thousands of novel IRESs in human and viruses, the next challenge is to decipher the sequence determinants of IRES activity...
September 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28636953/dicer-deficiency-differentially-impacts-microglia-of-the-developing-and-adult-brain
#5
Diana Varol, Alexander Mildner, Thomas Blank, Anat Shemer, Neta Barashi, Simon Yona, Eyal David, Sigalit Boura-Halfon, Yifat Segal-Hayoun, Louise Chappell-Maor, Hadas Keren-Shaul, Dena Leshkowitz, Eran Hornstein, Martin Fuhrmann, Ido Amit, Nicola Maggio, Marco Prinz, Steffen Jung
Microglia seed the embryonic neuro-epithelium, expand and actively sculpt neuronal circuits in the developing central nervous system, but eventually adopt relative quiescence and ramified morphology in the adult. Here, we probed the impact of post-transcriptional control by microRNAs (miRNAs) on microglial performance during development and adulthood by generating mice lacking microglial Dicer expression at these distinct stages. Conditional Dicer ablation in adult microglia revealed that miRNAs were required to limit microglial responses to challenge...
June 20, 2017: Immunity
https://www.readbyqxmd.com/read/28591632/bread-affects-clinical-parameters-and-induces-gut-microbiome-associated-personal-glycemic-responses
#6
Tal Korem, David Zeevi, Niv Zmora, Omer Weissbrod, Noam Bar, Maya Lotan-Pompan, Tali Avnit-Sagi, Noa Kosower, Gal Malka, Michal Rein, Jotham Suez, Ben Z Goldberg, Adina Weinberger, Avraham A Levy, Eran Elinav, Eran Segal
Bread is consumed daily by billions of people, yet evidence regarding its clinical effects is contradicting. Here, we performed a randomized crossover trial of two 1-week-long dietary interventions comprising consumption of either traditionally made sourdough-leavened whole-grain bread or industrially made white bread. We found no significant differential effects of bread type on multiple clinical parameters. The gut microbiota composition remained person specific throughout this trial and was generally resilient to the intervention...
June 6, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28507131/involvement-of-a-gut-retina-axis-in-protection-against-dietary-glycemia-induced-age-related-macular-degeneration
#7
Sheldon Rowan, Shuhong Jiang, Tal Korem, Jedrzej Szymanski, Min-Lee Chang, Jason Szelog, Christa Cassalman, Kalavathi Dasuri, Christina McGuire, Ryoji Nagai, Xue-Liang Du, Michael Brownlee, Naila Rabbani, Paul J Thornalley, James D Baleja, Amy A Deik, Kerry A Pierce, Justin M Scott, Clary B Clish, Donald E Smith, Adina Weinberger, Tali Avnit-Sagi, Maya Lotan-Pompan, Eran Segal, Allen Taylor
Age-related macular degeneration (AMD) is the major cause of blindness in developed nations. AMD is characterized by retinal pigmented epithelial (RPE) cell dysfunction and loss of photoreceptor cells. Epidemiologic studies indicate important contributions of dietary patterns to the risk for AMD, but the mechanisms relating diet to disease remain unclear. Here we investigate the effect on AMD of isocaloric diets that differ only in the type of dietary carbohydrate in a wild-type aged-mouse model. The consumption of a high-glycemia (HG) diet resulted in many AMD features (AMDf), including RPE hypopigmentation and atrophy, lipofuscin accumulation, and photoreceptor degeneration, whereas consumption of the lower-glycemia (LG) diet did not...
May 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28471480/microrna-142-controls-thymocyte-proliferation
#8
Alexander Mildner, Elik Chapnik, Diana Varol, Tegest Aychek, Nardi Lampl, Natalia Rivkin, Anita Bringmann, Franziska Paul, Sigalit Boura-Halfon, Yifat Segal Hayoun, Zohar Barnett-Itzhaki, Ido Amit, Eran Hornstein, Steffen Jung
T-cell development is a spatially and temporally regulated process, orchestrated by well-defined contributions of transcription factors and cytokines. Here, we identify the noncoding RNA miR-142 as an additional regulatory layer within murine thymocyte development and proliferation. MiR-142 deficiency impairs the expression of cell cycle-promoting genes in mature mouse thymocytes and early progenitors, accompanied with increased levels of cyclin-dependent kinase inhibitor 1B (Cdkn1b, also known as p27(Kip1) )...
July 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28250019/corrigendum-large-scale-mapping-of-gene-regulatory-logic-reveals-context-dependent-repression-by-transcriptional-activators
#9
David van Dijk, Eilon Sharon, Maya Lotan-Pompan, Adina Weinberger, Eran Segal, Lucas B Carey
No abstract text is available yet for this article.
March 2017: Genome Research
https://www.readbyqxmd.com/read/28212748/systematic-investigation-of-transcription-factor-activity-in-the-context-of-chromatin-using-massively-parallel-binding-and-expression-assays
#10
Michal Levo, Tali Avnit-Sagi, Maya Lotan-Pompan, Yael Kalma, Adina Weinberger, Zohar Yakhini, Eran Segal
Precise gene expression patterns are established by transcription factor (TFs) binding to regulatory sequences. While these events occur in the context of chromatin, our understanding of how TF-nucleosome interplay affects gene expression is highly limited. Here, we present an assay for high-resolution measurements of both DNA occupancy and gene expression on large-scale libraries of systematically designed regulatory sequences. Our assay reveals occupancy patterns at the single-cell level. It provides an accurate quantification of the fraction of the population bound by a nucleosome and captures distinct, even adjacent, TF binding events...
February 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/27965290/large-scale-mapping-of-gene-regulatory-logic-reveals-context-dependent-repression-by-transcriptional-activators
#11
David van Dijk, Eilon Sharon, Maya Lotan-Pompan, Adina Weinberger, Eran Segal, Lucas B Carey
Transcription factors (TFs) are key mediators that propagate extracellular and intracellular signals through to changes in gene expression profiles. However, the rules by which promoters decode the amount of active TF into target gene expression are not well understood. To determine the mapping between promoter DNA sequence, TF concentration, and gene expression output, we have conducted in budding yeast a large-scale measurement of the activity of thousands of designed promoters at six different levels of TF...
January 2017: Genome Research
https://www.readbyqxmd.com/read/27912059/microbiota-diurnal-rhythmicity-programs-host-transcriptome-oscillations
#12
Christoph A Thaiss, Maayan Levy, Tal Korem, Lenka Dohnalová, Hagit Shapiro, Diego A Jaitin, Eyal David, Deborah R Winter, Meital Gury-BenAri, Evgeny Tatirovsky, Timur Tuganbaev, Sara Federici, Niv Zmora, David Zeevi, Mally Dori-Bachash, Meirav Pevsner-Fischer, Elena Kartvelishvily, Alexander Brandis, Alon Harmelin, Oren Shibolet, Zamir Halpern, Kenya Honda, Ido Amit, Eran Segal, Eran Elinav
The intestinal microbiota undergoes diurnal compositional and functional oscillations that affect metabolic homeostasis, but the mechanisms by which the rhythmic microbiota influences host circadian activity remain elusive. Using integrated multi-omics and imaging approaches, we demonstrate that the gut microbiota features oscillating biogeographical localization and metabolome patterns that determine the rhythmic exposure of the intestinal epithelium to different bacterial species and their metabolites over the course of a day...
December 1, 2016: Cell
https://www.readbyqxmd.com/read/27906159/persistent-microbiome-alterations-modulate-the-rate-of-post-dieting-weight-regain
#13
Christoph A Thaiss, Shlomik Itav, Daphna Rothschild, Mariska Meijer, Maayan Levy, Claudia Moresi, Lenka Dohnalová, Sofia Braverman, Shachar Rozin, Sergey Malitsky, Mally Dori-Bachash, Yael Kuperman, Inbal Biton, Arieh Gertler, Alon Harmelin, Hagit Shapiro, Zamir Halpern, Asaph Aharoni, Eran Segal, Eran Elinav
In tackling the obesity pandemic, significant efforts are devoted to the development of effective weight reduction strategies, yet many dieting individuals fail to maintain a long-term weight reduction, and instead undergo excessive weight regain cycles. The mechanisms driving recurrent post-dieting obesity remain largely elusive. Here, we identify an intestinal microbiome signature that persists after successful dieting of obese mice, which contributes to faster weight regain and metabolic aberrations upon re-exposure to obesity-promoting conditions and transmits the accelerated weight regain phenotype upon inter-animal transfer...
November 24, 2016: Nature
https://www.readbyqxmd.com/read/27545349/massively-parallel-interrogation-of-the-effects-of-gene-expression-levels-on-fitness
#14
Leeat Keren, Jean Hausser, Maya Lotan-Pompan, Ilya Vainberg Slutskin, Hadas Alisar, Sivan Kaminski, Adina Weinberger, Uri Alon, Ron Milo, Eran Segal
Data of gene expression levels across individuals, cell types, and disease states is expanding, yet our understanding of how expression levels impact phenotype is limited. Here, we present a massively parallel system for assaying the effect of gene expression levels on fitness in Saccharomyces cerevisiae by systematically altering the expression level of ∼100 genes at ∼100 distinct levels spanning a 500-fold range at high resolution. We show that the relationship between expression levels and growth is gene and environment specific and provides information on the function, stoichiometry, and interactions of genes...
August 25, 2016: Cell
https://www.readbyqxmd.com/read/27443512/patterns-and-prognostic-relevance-of-pd-1-and-pd-l1-expression-in-colorectal-carcinoma
#15
Lik Hang Lee, Marcela S Cavalcanti, Neil H Segal, Jaclyn F Hechtman, Martin R Weiser, J Joshua Smith, Julio Garcia-Aguilar, Eran Sadot, Peter Ntiamoah, Arnold J Markowitz, Moshe Shike, Zsofia K Stadler, Efsevia Vakiani, David S Klimstra, Jinru Shia
Immune checkpoint blockade targeting the programmed death-1 (PD-1) pathway has shown efficacy in several types of cancers including mismatch-repair-deficient colorectal carcinoma. In some tumor types, programmed death-ligand 1 (PD-L1) expression detected by immunohistochemistry has shown utility as a predictive marker for response to anti-PD-1 therapies. This utility, however, remains to be determined in colorectal carcinoma. In addition, although tumor-infiltrating lymphocytes have been associated with better prognosis in colorectal carcinoma, the prognostic value of PD-1 expression in these lymphocytes and its interaction with PD-L1 expression still await investigation...
November 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27442807/toward-a-systematic-understanding-of-translational-regulatory-elements-in-human-and-viruses
#16
Shira Weingarten-Gabbay, Eran Segal
Translational regulation is a critical step in the production of proteins from genomic material in both human and viruses. However, unlike other steps of the central dogma, such as transcriptional regulation, little is known about the cis-regulatory elements involved. In a recent study we devised a high-throughput bicistronic reporter assay for the discovery and the characterization of thousands of novel Internal Ribosome Entry Sites (IRESs) in human and hundreds of viral genomes. Our results provide insights into the landscape of IRES elements in human and viral transcripts and the cis-regulatory sequences underlying their activity...
October 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27073913/a-minimalistic-resource-allocation-model-to-explain-ubiquitous-increase-in-protein-expression-with-growth-rate
#17
Uri Barenholz, Leeat Keren, Eran Segal, Ron Milo
Most proteins show changes in level across growth conditions. Many of these changes seem to be coordinated with the specific growth rate rather than the growth environment or the protein function. Although cellular growth rates, gene expression levels and gene regulation have been at the center of biological research for decades, there are only a few models giving a base line prediction of the dependence of the proteome fraction occupied by a gene with the specific growth rate. We present a simple model that predicts a widely coordinated increase in the fraction of many proteins out of the proteome, proportionally with the growth rate...
2016: PloS One
https://www.readbyqxmd.com/read/26987366/talking-about-cross-talk-the-immune-system-and-the-microbiome
#18
David Zeevi, Tal Korem, Eran Segal
A report on the first EMBO conference entitled "Next Gen Immunology-From Host Genome to the Microbiome: Immunity in the Genomic Era", held at the Weizmann Institute of Science, Israel, 14-16 February, 2016.
March 17, 2016: Genome Biology
https://www.readbyqxmd.com/read/26816383/comparative-genetics-systematic-discovery-of-cap-independent-translation-sequences-in-human-and-viral-genomes
#19
COMPARATIVE STUDY
Shira Weingarten-Gabbay, Shani Elias-Kirma, Ronit Nir, Alexey A Gritsenko, Noam Stern-Ginossar, Zohar Yakhini, Adina Weinberger, Eran Segal
To investigate gene specificity at the level of translation in both the human genome and viruses, we devised a high-throughput bicistronic assay to quantify cap-independent translation. We uncovered thousands of novel cap-independent translation sequences, and we provide insights on the landscape of translational regulation in both humans and viruses. We find extensive translational elements in the 3' untranslated region of human transcripts and the polyprotein region of uncapped RNA viruses. Through the characterization of regulatory elements underlying cap-independent translation activity, we identify potential mechanisms of secondary structure, short sequence motif, and base pairing with the 18S ribosomal RNA (rRNA)...
January 15, 2016: Science
https://www.readbyqxmd.com/read/26780094/integrative-genomic-analysis-by-interoperation-of-bioinformatics-tools-in-genomespace
#20
Kun Qu, Sara Garamszegi, Felix Wu, Helga Thorvaldsdottir, Ted Liefeld, Marco Ocana, Diego Borges-Rivera, Nathalie Pochet, James T Robinson, Barry Demchak, Tim Hull, Gil Ben-Artzi, Daniel Blankenberg, Galt P Barber, Brian T Lee, Robert M Kuhn, Anton Nekrutenko, Eran Segal, Trey Ideker, Michael Reich, Aviv Regev, Howard Y Chang, Jill P Mesirov
Complex biomedical analyses require the use of multiple software tools in concert and remain challenging for much of the biomedical research community. We introduce GenomeSpace (http://www.genomespace.org), a cloud-based, cooperative community resource that currently supports the streamlined interaction of 20 bioinformatics tools and data resources. To facilitate integrative analysis by non-programmers, it offers a growing set of 'recipes', short workflows to guide investigators through high-utility analysis tasks...
March 2016: Nature Methods
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