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Combinatorial genomics

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https://www.readbyqxmd.com/read/28733422/differences-in-dna-binding-specificity-of-floral-homeotic-protein-complexes-predict-organ-specific-target-genes
#1
Cezary Smaczniak, Jose M Muiño, Dijun Chen, Gerco C Angenent, Kerstin Kaufmann
Floral organ identities in plants are specified by the combinatorial action of homeotic master regulatory transcription factors. How these factors achieve their regulatory specificities is however still largely unclear. Genome-wide in vivo DNA binding data show that homeotic MADS-domain proteins recognize partly distinct genomic regions, suggesting that DNA binding specificity contributes to functional differences of homeotic protein complexes. We used in vitro systematic evolution of ligands by exponential enrichment followed by high throughput DNA sequencing (SELEX-seq) on several floral MADS-domain protein homo- and heterodimers to measure their DNA-binding specificities...
July 21, 2017: Plant Cell
https://www.readbyqxmd.com/read/28732207/a-crispr-resource-for-individual-combinatorial-or-multiplexed-gene-knockout
#2
Nicolas Erard, Simon R V Knott, Gregory J Hannon
We have combined a machine-learning approach with other strategies to optimize knockout efficiency with the CRISPR/Cas9 system. In addition, we have developed a multiplexed sgRNA expression strategy that promotes the functional ablation of single genes and allows for combinatorial targeting. These strategies have been combined to design and construct a genome-wide, sequence-verified, arrayed CRISPR library. This resource allows single-target or combinatorial genetic screens to be carried out at scale in a multiplexed or arrayed format...
July 20, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28718419/targeting-pi3k-signaling-in-combination-cancer-therapy
#3
REVIEW
Elvire Pons-Tostivint, Benoît Thibault, Julie Guillermet-Guibert
Targeting upstream phosphatidylinositol-3-kinases (PI3Ks) in the PI3K/Akt/mTOR pathway appears to be a promising therapy in solid cancers; however, first early clinical trials with PI3K inhibitors in monotherapy have been disappointing. A massive array of preclinical and clinical trials are currently evaluating combinations of PI3K inhibitors in targeted therapies. These combinations include co-treatments with drugs directed against other intra-/extracellular signaling molecules, nuclear hormone receptors, DNA damage repair enzymes, and immune modulators...
June 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28716409/from-experiment-driven-database-analyses-to-database-driven-experiments-in-arabidopsis-thaliana-transcription-factor-research
#4
REVIEW
Reinhard Hehl
Experiment-driven database analysis is employed in forward genetics to predict the function of genes assocíated with a mutant phenotype. These analyses subsequently lead to database-driven experiments involving reverse genetics to verify functional predictions based on bioinformatic analyses. Genomic transcription factors (TFs) are key regulators of gene expression by binding to short regulatory sequences and by interacting with other TFs. Currently more than 2400 TFs are predicted for A. thaliana. As DNA-binding proteins they are particularly amenable to database-driven experiments, especially when their binding site specificities are known...
September 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28716006/ethylene-induces-combinatorial-effects-of-histone-h3-acetylation-in-gene-expression-in-arabidopsis
#5
Likai Wang, Fan Zhang, Siddharth Rode, Kevin K Chin, Eun Esther Ko, Jonghwan Kim, Vishwanath R Iyer, Hong Qiao
BACKGROUND: Histone acetylation and deacetylation are essential for gene regulation and have been implicated in the regulation of plant hormone responses. Many studies have indicated the role of histone acetylation in ethylene signaling; however, few studies have investigated how ethylene signaling regulates the genomic landscape of chromatin states. Recently, we found that ethylene can specifically elevate histone H3K14 acetylation and the non-canonical histone H3K23 acetylation in etiolated seedlings and the gene activation is positively associated with the elevation of H3K14Ac and H3K23Ac in response to ethylene...
July 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28714992/musashi-1-regulates-the-timing-and-extent-of-meiotic-mrna-translational-activation-by-promoting-the-use-of-specific-cpes
#6
Laure Weill, Eulàlia Belloc, Chiara Lara Castellazzi, Raúl Méndez
The translational reactivation of maternal mRNAs encoding meiotic drivers in vertebrates is accomplished mainly by cytoplasmic polyadenylation. The cytoplasmic polyadenylation elements (CPEs) present in the 3' untranslated regions (3' UTRs) of these transcripts, together with their cognate CPE-binding proteins (CPEBs), define a combinatorial code that determines the timing and extent of translational activation upon meiosis resumption. In addition, the RNA-binding protein Musashi1 (Msi1) regulates polyadenylation of CPE-containing mRNAs by a yet undefined CPEB-dependent or CPEB-independent mechanism...
July 17, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28711868/human-ttbk1-ttbk2-and-mark1-kinase-toxicity-in-drosophila-melanogaster-is-exacerbated-by-co-expression-of-human-tau
#7
Josefin Fernius, Annika Starkenberg, Malgorzata Pokrzywa, Stefan Thor
Tau protein is involved in numerous human neurodegenerative diseases, and Tau hyper-phosphorylation has been linked to Tau aggregation and toxicity. Previous studies have addressed toxicity and phospho-biology of human Tau (hTau) in Drosophila melanogaster However, hTau transgenes have most often been randomly inserted in the genome, thus making it difficult to compare between different hTau isoforms and phospho-mutants. In addition, many studies have expressed hTau also in mitotic cells, causing non-physiological toxic effects...
July 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28705894/genome-wide-analysis-of-facial-skeletal-regionalization-in-zebrafish
#8
Amjad Askary, Pengfei Xu, Lindsey Barske, Maxwell Bay, Paul Bump, Bartosz Balczerski, Michael A Bonaguidi, J Gage Crump
Patterning of the facial skeleton involves the precise deployment of thousands of genes in distinct regions of the pharyngeal arches. Despite the significance for craniofacial development, how genetic programs drive this regionalization remains incompletely understood. Here we use combinatorial labeling of zebrafish cranial neural crest-derived cells (CNCCs) to define global gene expression along the dorsoventral axis of the developing arches. Intersection of region-specific transcriptomes with expression changes in response to signaling perturbations demonstrates complex roles for Endothelin1 (Edn1) signaling in the intermediate joint-forming region, yet a surprisingly minor role in ventral-most regions...
July 13, 2017: Development
https://www.readbyqxmd.com/read/28692336/positive-selection-analysis-highlights-key-positions-in-plant-pp2a-regulatory-subunits
#9
Matthew A Booker, Alison DeLong
A versatile hub for cellular control, the eukaryotic protein phosphatase 2A (PP2A) enzyme family is thought to achieve specificity through combinatorial complexity. Phylogenetic analysis has revealed that expansion of PP2A gene families resulted from whole genome duplications followed by non-random gene loss, and selection analysis suggests that retention of B56/PPP2R5 gene family members after genome duplication events was driven by functional diversification. Here we identify the sites at which positive selection is detected in the plant B56 gene family, and discuss the significance of selection at these positions in the context of PP2A holoenzyme structure...
July 10, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28687337/a-translational-synthetic-biology-platform-for-rapid-access-to-gram-scale-quantities-of-novel-drug-like-molecules
#10
James Reed, Michael J Stephenson, Karel Miettinen, Bastiaan Brouwer, Aymeric Leveau, Paul Brett, Rebecca J M Goss, Alain Goossens, Maria A O'Connell, Anne Osbourn
Plants are an excellent source of drug leads. However availability is limited by access to source species, low abundance and recalcitrance to chemical synthesis. Although plant genomics is yielding a wealth of genes for natural product biosynthesis, the translation of this genetic information into small molecules for evaluation as drug leads represents a major bottleneck. For example, the yeast platform for artemisinic acid production is estimated to have taken >150 person years to develop. Here we demonstrate the power of plant transient transfection technology for rapid, scalable biosynthesis and isolation of triterpenes, one of the largest and most structurally diverse families of plant natural products...
July 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28676447/profiling-conserved-biological-pathways-in-autosomal-dominant-polycystic-kidney-disorder-adpkd-to-elucidate-key-transcriptomic-alterations-regulating-cystogenesis-a-cross-species-meta-analysis-approach
#11
REVIEW
Shatakshee Chatterjee, Srikant Prasad Verma, Priyanka Pandey
PURPOSE: Initiation and progression of fluid filled cysts mark Autosomal Dominant Polycystic Kidney Disease (ADPKD). Thus, improved therapeutics targeting cystogenesis remains a constant challenge. Microarray studies in single ADPKD animal models species with limited sample sizes tend to provide scattered views on underlying ADPKD pathogenesis. Thus we aim to perform a cross species meta-analysis to profile conserved biological pathways that might be key targets for therapy. METHODS: Nine ADPKD microarray datasets on rat, mice and human fulfilled our study criteria and were chosen...
July 1, 2017: Gene
https://www.readbyqxmd.com/read/28665995/transcriptomes-of-six-mutants-in-the-sen1-pathway-reveal-combinatorial-control-of-transcription-termination-across-the-saccharomyces-cerevisiae-genome
#12
Xin Chen, Kunal Poorey, Melissa N Carver, Ulrika Müller, Stefan Bekiranov, David T Auble, David A Brow
Transcriptome studies on eukaryotic cells have revealed an unexpected abundance and diversity of noncoding RNAs synthesized by RNA polymerase II (Pol II), some of which influence the expression of protein-coding genes. Yet, much less is known about biogenesis of Pol II non-coding RNA than mRNAs. In the budding yeast Saccharomyces cerevisiae, initiation of non-coding transcripts by Pol II appears to be similar to that of mRNAs, but a distinct pathway is utilized for termination of most non-coding RNAs: the Sen1-dependent or "NNS" pathway...
June 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28664268/biased-selection-of-propagation-related-tups-from-phage-display-peptide-libraries
#13
REVIEW
Hesam Motaleb Zade, Reihaneh Keshavarz, Hosna Sadat Zahed Shekarabi, Babak Bakhshinejad
Phage display is rapidly advancing as a screening strategy in drug discovery and drug delivery. Phage-encoded combinatorial peptide libraries can be screened through the affinity selection procedure of biopanning to find pharmaceutically relevant cell-specific ligands. However, the unwanted enrichment of target-unrelated peptides (TUPs) with no true affinity for the target presents an important barrier to the successful screening of phage display libraries. Propagation-related TUPs (Pr-TUPs) are an emerging but less-studied category of phage display-derived false-positive hits that are displayed on the surface of clones with faster propagation rates...
June 29, 2017: Amino Acids
https://www.readbyqxmd.com/read/28650219/interrogating-cell-division-errors-using-random-and-chromosome-specific-missegregation-approaches
#14
Peter Ly, Don W Cleveland
Accurate segregation of the duplicated genome in mitosis is essential for maintaining genetic stability. Errors in this process can cause numerical and/or structural chromosome abnormalities - hallmark genomic features commonly associated with both tumorigenesis and developmental disorders. A cell-based approach was recently developed permitting inducible missegregation of the human Y chromosome by selectively disrupting kinetochore assembly onto the Y centromere. Although this strategy initially requires several steps of genetic manipulation, it is easy to use, highly efficient and specific for the Y without affecting the autosomes or the X, and does not require cell cycle synchronization or mitotic perturbation...
June 26, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28649005/crispr-cas9-coupled-recombineering-for-metabolic-engineering-of-corynebacterium-glutamicum
#15
Jae Sung Cho, Kyeong Rok Choi, Cindy Pricilia Surya Prabowo, Jae Ho Shin, Dongsoo Yang, Jaedong Jang, Sang Yup Lee
Genome engineering of Corynebacterium glutamicum, an important industrial microorganism for amino acids production, currently relies on random mutagenesis and inefficient double crossover events. Here we report a rapid genome engineering strategy to scarlessly knock out one or more genes in C. glutamicum in sequential and iterative manner. Recombinase RecT is used to incorporate synthetic single-stranded oligodeoxyribonucleotides into the genome and CRISPR/Cas9 to counter-select negative mutants. We completed the system by engineering the respective plasmids harboring CRISPR/Cas9 and RecT for efficient curing such that multiple gene targets can be done iteratively and final strains will be free of plasmids...
July 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28645527/inhibition-of-17beta-hydroxysteroid-dehydrogenase-type-7-modulates-breast-cancer-protein-profile-and-enhances-apoptosis-by-down-regulating-grp78
#16
Xiao-Qiang Wang, Juliette A Aka, Tang Li, Dan Xu, Charles J Doillon, Sheng-Xiang Lin
17beta-hydroxysteroid dehydrogenase type 7 (17β-HSD7) promotes breast cancer cell growth via dual-catalytic activity by modulating estradiol and DHT. Here, we clarified the expression pattern of 17β-HSD7 in postmenopausal luminal A type breast cancer with The Cancer Genome Atlas (TCGA) cohort. The impact of 17β-HSD7 inhibition on the proteome of MCF-7 cells was investigated and on cell apoptosis was revealed. MCF-7 cells were treated with an efficient inhibitor of 17β-HSD7 or with vehicle, and a differential proteomics study was performed using two-dimensional (2D) gel electrophoresis followed by mass spectrometry and ingenuity pathway analysis (IPA)...
June 20, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28630873/an-integrative-developmental-genomics-and-systems-biology-approach-to-identify-an-in-vivo-sox-trio-mediated-gene-regulatory-network-in-murine-embryos
#17
Wenqing Jean Lee, Sumantra Chatterjee, Sook Peng Yap, Siew Lan Lim, Xing Xing, Petra Kraus, Wenjie Sun, Xiaoming Hu, V Sivakamasundari, Hsiao Yun Chan, Prasanna R Kolatkar, Shyam Prabhakar, Thomas Lufkin
Embryogenesis is an intricate process involving multiple genes and pathways. Some of the key transcription factors controlling specific cell types are the Sox trio, namely, Sox5, Sox6, and Sox9, which play crucial roles in organogenesis working in a concerted manner. Much however still needs to be learned about their combinatorial roles during this process. A developmental genomics and systems biology approach offers to complement the reductionist methodology of current developmental biology and provide a more comprehensive and integrated view of the interrelationships of complex regulatory networks that occur during organogenesis...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28623575/from-genes-to-networks-characterizing-gene-regulatory-interactions-in-plants
#18
Kerstin Kaufmann, Dijun Chen
Plants, like other eukaryotes, have evolved complex mechanisms to coordinate gene expression during development, environmental response, and cellular homeostasis. Transcription factors (TFs), accompanied by basic cofactors and posttranscriptional regulators, are key players in gene-regulatory networks (GRNs). The coordinated control of gene activity is achieved by the interplay of these factors and by physical interactions between TFs and DNA. Here, we will briefly outline recent technological progress made to elucidate GRNs in plants...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28611825/epigenetic-combinatorial-patterns-predict-disease-variants
#19
Yu Zhang
Most genetic variants identified in genome-wide association studies are noncoding and are likely tagging nearby causal variants. It is a challenging task to pinpoint the precise locations of disease-causal variants and understand their functions in disease. A promising approach to improve fine mapping is to integrate the functional data currently available on hundreds of human tissues and cell types. Although there are several methods that use functional data to prioritize disease variants, they mainly use linear models, or equivalent naive likelihood-based models for prediction...
2017: Frontiers in Genetics
https://www.readbyqxmd.com/read/28600722/genetic-dissection-of-plant-growth-habit-in-chickpea
#20
Hari D Upadhyaya, Deepak Bajaj, Rishi Srivastava, Anurag Daware, Udita Basu, Shailesh Tripathi, Chellapilla Bharadwaj, Akhilesh K Tyagi, Swarup K Parida
A combinatorial genomics-assisted breeding strategy encompassing association analysis, genetic mapping and expression profiling is found most promising for quantitative dissection of complex traits in crop plants. The present study employed GWAS (genome-wide association study) using 24,405 SNPs (single nucleotide polymorphisms) obtained with genotyping-by-sequencing (GBS) of 92 sequenced desi and kabuli accessions of chickpea. This identified eight significant genomic loci associated with erect (E)/semi-erect (SE) vs...
June 9, 2017: Functional & Integrative Genomics
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