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Enhancer drosophila

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https://www.readbyqxmd.com/read/28088785/the-igh-locus-3-cis-regulatory-super-enhancer-co-opts-aid-for-allelic-transvection
#1
Sandrine Le Noir, Brice Laffleur, Claire Carrion, Armand Garot, Sandrine Lecardeur, Eric Pinaud, Yves Denizot, Jane Skok, Michel Cogné
Immunoglobulin heavy chain (IgH) alleles have ambivalent relationships: they feature both allelic exclusion, ensuring monoallelic expression of a single immunoglobulin (Ig) allele, and frequent inter-allelic class-switch recombination (CSR) reassembling genes from both alleles. The IgH locus 3' regulatory region (3'RR) includes several transcriptional cis-enhancers promoting activation-induced cytidine deaminase (AID)-dependent somatic hypermutation (SHM) and CSR, and altogether behaves as a strong super-enhancer...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077717/complexin-mutants-reveal-partial-segregation-between-recycling-pathways-that-drive-evoked-and-spontaneous-neurotransmission
#2
Nadezhda Sabeva, Richard W Cho, Alexander Vasin, Agustin Gonzalez, J Troy Littleton, Maria Bykhovskaia
: Synaptic vesicles fuse at morphological specializations in the presynaptic terminal termed active zones (AZs). Vesicle fusion can occur spontaneously or in response to an action potential. Following fusion, vesicles are retrieved and recycled within nerve terminals. It is still unclear whether vesicles that fuse spontaneously or following evoked release share similar recycling mechanisms. Genetic deletion of the SNARE-binding protein complexin dramatically increases spontaneous fusion, with the protein serving as the synaptic vesicle fusion clamp at Drosophila synapses...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28077621/functional-redundancy-and-non-redundancy-between-two-troponin-c-isoforms-in-drosophila-adult-muscles
#3
Maria B Chechenova, Sara Maes, Sandy T Oas, Cloyce Nelson, Kaveh G Kiani, Anton L Bryantsev, Richard M Cripps
We investigated the functional overlap of two muscle Troponin C (TpnC) genes that are expressed in the adult fruit fly, Drosophila melanogaster: TpnC4 is predominantly expressed in the indirect flight muscles (IFM), whereas TpnC41C is the main isoform in the tergal depressor of the trochanter muscle (TDT or jump muscle). Using CRISPR/Cas9, we created a transgenic line with a homozygous deletion of TpnC41C, and compared its phenotype to a line lacking functional TpnC4 We found that the removal of either of these genes leads to expression of the other isoform in both muscle types...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28077616/different-modes-of-enhancer-specific-regulation-by-runt-and-even-skipped-during-drosophila-segmentation
#4
Saiyu Hang, J Peter Gergen
The initial metameric expression of the Drosophila sloppy paired 1 (slp1) gene is controlled by two distinct cis-regulatory DNA elements that interact in a non-additive manner to integrate inputs from transcription factors encoded by the pair-rule segmentation genes. We performed Chromatin Immuno-Precipitation (ChIP) on reporter genes containing these elements in different embryonic genotypes to investigate the mechanism of their regulation. The Distal Early Stripe Element (DESE) mediates both activation and repression by Runt...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28068320/myc-suppresses-tumor-invasion-and-cell-migration-by-inhibiting-jnk-signaling
#5
X Ma, J Huang, Y Tian, Y Chen, Y Yang, X Zhang, F Zhang, L Xue
Tumor metastasis, but not primary overgrowth, is the leading cause of mortality for cancer patients. During the past decade, Drosophila melanogaster has been well-accepted as an excellent model to address the intrinsic mechanism of different aspects of cancer progression, ranging from tumor initiation to metastasis. In a genetic screen performed in Drosophila, aiming to find novel modulators of tumor invasion, we identified the oncoprotein Myc as a negative regulator. While expression of Myc dramatically blocks tumor invasion and cell migration, loss of Myc promotes cell migration in vivo...
January 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28057308/drosophila-as-a-model-for-diabetes-and-diseases-of-insulin-resistance
#6
P Graham, L Pick
Despite the importance of insulin signaling pathways in human disease, initial concerns that insect physiology and sugar metabolism differ enough from humans that flies would not model human disease hampered research in this area. However, during the past 10-15 years, evidence has accumulated that flies can indeed model various aspects of diabetes and related human disorders. This cluster of diseases impact insulin and insulin signaling pathways, fields which have been discussed in many excellent review articles in recent years...
2017: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/28053067/drug-discovery-in-fish-flies-and-worms
#7
Kevin Strange
Nonmammalian model organisms such as the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the zebrafish Danio rerio provide numerous experimental advantages for drug discovery including genetic and molecular tractability, amenability to high-throughput screening methods and reduced experimental costs and increased experimental throughput compared to traditional mammalian models. An interdisciplinary approach that strategically combines the study of nonmammalian and mammalian animal models with diverse experimental tools has and will continue to provide deep molecular and genetic understanding of human disease and will significantly enhance the discovery and application of new therapies to treat those diseases...
December 2016: ILAR Journal
https://www.readbyqxmd.com/read/28052257/a-fully-synthetic-transcriptional-platform-for-a-multicellular-eukaryote
#8
Justin Crocker, Albert Tsai, David L Stern
Regions of genomic DNA called enhancers encode binding sites for transcription factor proteins. Binding of activators and repressors increase and reduce transcription, respectively, but it is not understood how combinations of activators and repressors generate precise patterns of transcription during development. Here, we explore this problem using a fully synthetic transcriptional platform in Drosophila consisting of engineered transcription factor gradients and artificial enhancers. We found that binding sites for a transcription factor that makes DNA accessible are required together with binding sites for transcriptional activators to produce a functional enhancer...
January 3, 2017: Cell Reports
https://www.readbyqxmd.com/read/28032862/cullin-4-regulates-wingless-and-jnk-signaling-mediated-cell-death-in-the-drosophila-eye
#9
Meghana Tare, Ankita Sarkar, Shimpi Bedi, Madhuri Kango-Singh, Amit Singh
In all multicellular organisms, the fundamental processes of cell proliferation and cell death are crucial for growth regulation during organogenesis. Strict regulation of cell death is important to maintain tissue homeostasis by affecting processes like regulation of cell number, and elimination of unwanted/unfit cells. The developing Drosophila eye is a versatile model to study patterning and growth, where complex signaling pathways regulate growth and cell survival. However, the molecular mechanisms underlying regulation of these processes is not fully understood...
December 29, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/28024300/genetic-variants-regulating-expression-levels-and-isoform-diversity-during-embryogenesis
#10
Enrico Cannavò, Nils Koelling, Dermot Harnett, David Garfield, Francesco P Casale, Lucia Ciglar, Hilary E Gustafson, Rebecca R Viales, Raquel Marco-Ferreres, Jacob F Degner, Bingqing Zhao, Oliver Stegle, Ewan Birney, Eileen E M Furlong
Embryonic development is driven by tightly regulated patterns of gene expression, despite extensive genetic variation among individuals. Studies of expression quantitative trait loci (eQTL) indicate that genetic variation frequently alters gene expression in cell-culture models and differentiated tissues. However, the extent and types of genetic variation impacting embryonic gene expression, and their interactions with developmental programs, remain largely unknown. Here we assessed the effect of genetic variation on transcriptional (expression levels) and post-transcriptional (3' RNA processing) regulation across multiple stages of metazoan development, using 80 inbred Drosophila wild isolates, identifying thousands of developmental-stage-specific and shared QTL...
January 19, 2017: Nature
https://www.readbyqxmd.com/read/28024147/genome-wide-assessment-of-sequence-intrinsic-enhancer-responsiveness-at-single-base-pair-resolution
#11
Cosmas D Arnold, Muhammad A Zabidi, Michaela Pagani, Martina Rath, Katharina Schernhuber, Tomáš Kazmar, Alexander Stark
Gene expression is controlled by enhancers that activate transcription from the core promoters of their target genes. Although a key function of core promoters is to convert enhancer activities into gene transcription, whether and how strongly they activate transcription in response to enhancers has not been systematically assessed on a genome-wide level. Here we describe self-transcribing active core promoter sequencing (STAP-seq), a method to determine the responsiveness of genomic sequences to enhancers, and apply it to the Drosophila melanogaster genome...
December 26, 2016: Nature Biotechnology
https://www.readbyqxmd.com/read/28011637/tribbles-pseudokinase-3-induces-both-apoptosis-and-autophagy-in-amyloid-%C3%AE-induced-neuronal-death
#12
Suraiya Saleem, Subhas Chandra Biswas
Amyloid-β (Aβ) induced neuron death is considered central to the pathogenesis of Alzheimer disease (AD). Among several death modalities, autophagy and apoptosis play important roles in Aβ-induced neuron death suggesting that there may be regulatory mechanisms that initiate both cell death pathways. However, molecules that govern both pathways have not been identified. Here, we report that, upon Aβ treatment, tribbles pseudokinase 3 (TRIB3, an ortholog of Drosophila Tribbles), is upregulated in neurons, both in vivo and in vitro...
December 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28011627/enhancing-nad-salvage-metabolism-is-neuroprotective-in-a-pink1-model-of-parkinson-s-disease
#13
Susann Lehmann, Samantha H Y Loh, L Miguel Martins
Familial forms of Parkinson's disease (PD) caused by mutations in PINK1 are linked to mitochondrial impairment. Defective mitochondria are also found in Drosophila models of PD with pink1 mutations. The co-enzyme nicotinamide adenine dinucleotide (NAD(+)) is essential for both generating energy in mitochondria and nuclear DNA repair through NAD(+)-consuming poly(ADP-ribose) polymerases (PARPs). We found alterations in NAD(+) salvage metabolism in Drosophila pink1 mutants and showed that a diet supplemented with the NAD(+) precursor nicotinamide rescued mitochondrial defects and protected neurons from degeneration...
December 23, 2016: Biology Open
https://www.readbyqxmd.com/read/28010188/the-in-vivo-genetic-toolkit-for-studying-expression-and-functions-of-drosophila-melanogaster-micrornas
#14
Hina Iftikhar, Janna N Schultzhaus, Chloe J Bennett, Ginger E Carney
Since the initial reports that a group of small RNAs, now known as microRNAs (miRNAs), regulates gene expression without being translated into proteins, there has been an explosion of studies on these important expression modulators. Drosophila melanogaster has proven to be one of the most amenable animal models for investigations of miRNA biogenesis and gene regulatory activities. Here, we highlight the publicly available genetic tools and strategies for in vivo functional studies of miRNA activity in D. melanogaster...
December 23, 2016: RNA Biology
https://www.readbyqxmd.com/read/28009299/ret-functions-as-a-dual-specificity-kinase-that-requires-allosteric-inputs-from-juxtamembrane-elements
#15
Iván Plaza-Menacho, Karin Barnouin, Rachael Barry, Annabel Borg, Mariam Orme, Rakhee Chauhan, Stephane Mouilleron, Rubén J Martínez-Torres, Pascal Meier, Neil Q McDonald
Receptor tyrosine kinases exhibit a variety of activation mechanisms despite highly homologous catalytic domains. Such diversity arises through coupling of extracellular ligand-binding portions with highly variable intracellular sequences flanking the tyrosine kinase domain and specific patterns of autophosphorylation sites. Here, we show that the juxtamembrane (JM) segment enhances RET catalytic domain activity through Y687. This phospho-site is also required by the JM region to rescue an otherwise catalytically deficient RET activation-loop mutant lacking tyrosines...
December 20, 2016: Cell Reports
https://www.readbyqxmd.com/read/27988233/identification-and-functional-analysis-of-pointed-homologs-in-bombyx-mori
#16
Hiromitsu Tanaka, Aki Sagisaka
Using gene-knockdown techniques, we searched for endogenous Ets family proteins involved in the regulation of Escherichia coli-dependent lebocin promoter activation in the E. coli-responsive silkworm cell line NIAS-Bm-aff3. Results showed that the gene knockdown of BmPointeds (BmPNTs), Drosophila Pointed orthologs, enhanced E. coli-dependent lebocin promoter activation, suggesting that endogenous BmPNTs repress the activation of this promoter. Furthermore, we found that i) the BmPNT gene produced at least two alternative splicing isoforms, BmPNT1 and BmPNT2, both of which function as repressors; ii) BmPNTs were not associated with an already-reported repressor element, most proximal GGAA/T motif (EtsRE3), in lebocin promoter, which plays a role in the repression of E...
March 10, 2017: Gene
https://www.readbyqxmd.com/read/27979994/drosophila-poised-enhancers-are-generated-during-tissue-patterning-with-the-help-of-repression
#17
Nina Koenecke, Jeff Johnston, Qiye He, Samuel Meier, Julia Zeitlinger
Histone modifications are frequently used as markers for enhancer states, but how to interpret enhancer states in the context of embryonic development is not clear. The poised enhancer signature, involving H3K4me1 and low levels of H3K27ac, has been reported to mark inactive enhancers that are poised for future activation. However, future activation is not always observed, and alternative reasons for the widespread occurrence of this enhancer signature have not been investigated. By analyzing enhancers during dorsal-ventral (DV) axis formation in the Drosophila embryo, we find that the poised enhancer signature is specifically generated during patterning in the tissue where the enhancers are not induced, including at enhancers that are known to be repressed by a transcriptional repressor...
January 2017: Genome Research
https://www.readbyqxmd.com/read/27979972/phosphorylation-by-nlk-inhibits-yap-14-3-3-interactions-and-induces-its-nuclear-localization
#18
Sungho Moon, Wantae Kim, Soyoung Kim, Youngeun Kim, Yonghee Song, Oleksii Bilousov, Jiyoung Kim, Taebok Lee, Boksik Cha, Minseong Kim, Hanjun Kim, Vladimir L Katanaev, Eek-Hoon Jho
Hippo signaling controls organ size by regulating cell proliferation and apoptosis. Yes-associated protein (YAP) is a key downstream effector of Hippo signaling, and LATS-mediated phosphorylation of YAP at Ser127 inhibits its nuclear localization and transcriptional activity. Here, we report that Nemo-like kinase (NLK) phosphorylates YAP at Ser128 both in vitro and in vivo, which blocks interaction with 14-3-3 and enhances its nuclear localization. Depletion of NLK increases YAP phosphorylation at Ser127 and reduces YAP-mediated reporter activity...
January 2017: EMBO Reports
https://www.readbyqxmd.com/read/27966490/ayurvedic-amalaki-rasayana-promotes-improved-stress-tolerance-and-thus-has-anti-aging-effects-in-drosophila-melanogaster
#19
Vibha Dwivedi, Subhash C Lakhotia
Amalaki Rasayana (AR) is a common Ayurvedic herbal formulation of Phyllanthus emblica fruits and some other ingredients, and is used for general good health and healthy aging. We reported it to improve life history traits and to suppress neurodegeneration as well as induced apoptosis in Drosophila. The present study examines responses of Drosophila reared on AR-supplemented food to crowding, thermal or oxidative stresses. Wild-type larvae/flies reared on AR-supplemented food survived the various cell stresses much better than those reared on control food...
December 2016: Journal of Biosciences
https://www.readbyqxmd.com/read/27956482/enhanced-fertility-and-chill-tolerance-after-cold-induced-reproductive-arrest-in-females-of-temperate-species-of-the-drosophila-buzzatii-complex
#20
Julián Mensch, Juan Hurtado, Paula F Zermoglio, Gerardo de la Vega, Carmen Rolandi, Pablo E Schilman, Therese A Markow, Esteban Hasson
Long-term exposure to low temperatures during the adult maturation might decrease fertility after cold recovery as a consequence of carry-over effects on reproductive tissues. This pattern should be more pronounced in tropical than in temperate species since protective mechanism against chilling injuries are expected to be more effective in the latter. We initially determined the lower thermal thresholds to induce ovarian maturation in four closely related Drosophila species, two inhabiting temperate regions and the other two tropical areas of South America...
December 12, 2016: Journal of Experimental Biology
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