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https://www.readbyqxmd.com/read/28735898/genome-wide-single-molecule-footprinting-reveals-high-rna-polymerase-ii-turnover-at-paused-promoters
#1
Arnaud R Krebs, Dilek Imanci, Leslie Hoerner, Dimos Gaidatzis, Lukas Burger, Dirk Schübeler
Transcription initiation entails chromatin opening followed by pre-initiation complex formation and RNA polymerase II recruitment. Subsequent polymerase elongation requires additional signals, resulting in increased residence time downstream of the start site, a phenomenon referred to as pausing. Here, we harnessed single-molecule footprinting to quantify distinct steps of initiation in vivo throughout the Drosophila genome. This identifies the impact of promoter structure on initiation dynamics in relation to nucleosomal occupancy...
July 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28728902/role-of-mirnas-in-development-and-disease-lessons-learnt-from-small-organisms
#2
REVIEW
Swati Chandra, Divya Vimal, Divya Sharma, Vipin Rai, Subash Chandra Gupta, D Kar Chowdhuri
MicroRNAs (miRNAs) constitute a class of small (21-24 nucleotides) non-coding RNAs that regulate gene expression at the post-transcriptional level. Caenorhabditis elegans, Drosophila melanogaster, and many other small organisms have been instrumental in deciphering the biological functions of miRNAs. While some miRNAs from small organisms are highly conserved across the taxa, others are organism specific. The miRNAs are known to play a crucial role during development and in various cellular functions such as cell survival, cell proliferation, and differentiation...
July 17, 2017: Life Sciences
https://www.readbyqxmd.com/read/28726107/studying-a-novel-ecdysone-dependent-enhancer
#3
J V Nikolenko, A N Krasnov, M Y Mazina, S G Georgieva, N E Vorobyeva
Earlier [4], we developed a two-stage scheme of the activation of expression of the ecdysone cascade gene ftz-f1 in Drosophila melanogaster S2 cells. In the first intron of the ftz-f1 gene, we found a binding site for the transcription activator DHR3. In this work, we studied the properties of this genomic element: the change in the histone modification level at different stages of transcription activation were analyzed, and data indicating the interaction of the intron element with the promoter were obtained...
May 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28720827/small-chaperons-and-autophagy-protected-neurons-from-necrotic-cell-death
#4
Ye Lei, Kai Liu, Lin Hou, Lianggong Ding, Yuhong Li, Lei Liu
Neuronal necrosis occurs during early phase of ischemic insult. However, our knowledge of neuronal necrosis is still inadequate. To study the mechanism of neuronal necrosis, we previously established a Drosophila genetic model of neuronal necrosis by calcium overloading through expression of a constitutively opened cation channel mutant. Here, we performed further genetic screens and identified a suppressor of neuronal necrosis, CG17259, which encodes a seryl-tRNA synthetase. We found that loss-of-function (LOF) CG17259 activated eIF2α phosphorylation and subsequent up-regulation of chaperons (Hsp26 and Hsp27) and autophagy...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720579/recruitment-of-histone-modifications-to-assist-mrna-dosage-maintenance-after-degeneration-of-cytosine-dna-methylation-during-animal-evolution
#5
Andrew Yf Chang, Ben-Yang Liao
Following gene duplication, mRNA expression of the duplicated gene is reduced to maintain mRNA dosage. In mammals, this process is achieved with increased cytosine DNA methylation of the promoters of duplicated genes to suppress transcriptional initiation. However, not all animal species possess a full apparatus for cytosine DNA methylation. For such species such as roundworm (Caenorhabditis elegans, "worm" hereafter) or fruit fly (Drosophila melanogaster, "fly" hereafter), it is unclear how reduced expression of duplicated genes has been achieved evolutionarily...
July 18, 2017: Genome Research
https://www.readbyqxmd.com/read/28716036/short-dna-sequence-patterns-accurately-identify-broadly-active-human-enhancers
#6
Laura L Colbran, Ling Chen, John A Capra
BACKGROUND: Enhancers are DNA regulatory elements that influence gene expression. There is substantial diversity in enhancers' activity patterns: some enhancers drive expression in a single cellular context, while others are active across many. Sequence characteristics, such as transcription factor (TF) binding motifs, influence the activity patterns of regulatory sequences; however, the regulatory logic through which specific sequences drive enhancer activity patterns is poorly understood...
July 17, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28715438/a-sequence-level-model-of-an-intact-locus-predicts-the-location-and-function-of-nonadditive-enhancers
#7
Kenneth A Barr, John Reinitz
Metazoan gene expression is controlled through the action of long stretches of noncoding DNA that contain enhancers-shorter sequences responsible for controlling a single aspect of a gene's expression pattern. Models built on thermodynamics have shown how enhancers interpret protein concentration in order to determine specific levels of gene expression, but the emergent regulatory logic of a complete regulatory locus shows qualitative and quantitative differences from isolated enhancers. Such differences may arise from steric competition limiting the quantity of DNA that can simultaneously influence the transcription machinery...
2017: PloS One
https://www.readbyqxmd.com/read/28715417/a-hox-complex-activates-and-potentiates-the-epidermal-growth-factor-signaling-pathway-to-specify-drosophila-oenocytes
#8
Guolun Wang, Lisa Gutzwiller, David Li-Kroeger, Brian Gebelein
Hox transcription factors specify distinct cell types along the anterior-posterior axis of metazoans by regulating target genes that modulate signaling pathways. A well-established example is the induction of Epidermal Growth Factor (EGF) signaling by an Abdominal-A (Abd-A) Hox complex during the specification of Drosophila hepatocyte-like cells (oenocytes). Previous studies revealed that Abd-A is non-cell autonomously required to promote oenocyte fate by directly activating a gene (rhomboid) that triggers EGF secretion from sensory organ precursor (SOP) cells...
July 17, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28712876/drosophila-sce-dring-e3-ligase-inhibits-apoptosis-in-a-dp53-dependent-manner
#9
Rocío Simón, Carolina J Simoes da Silva, Sol Fereres, Ana Busturia
The Polycomb group (PcG) of proteins control developmental gene silencing and are highly conserved between flies and mammals. PcG proteins function by controlling post-translational modification of histones, such as ubiquitylation, which impacts chromatin compaction and thus gene transcription. Changes in PcG cellular levels have drastic effects on organismal development and are involved in the generation of human pathologies such as cancer. However, the mechanisms controlling their levels of expression and their physiological effects are only partially understood...
July 13, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28711427/temporal-remodeling-of-the-cell-cycle-accompanies-differentiation-in-the-drosophila-germline
#10
Taylor D Hinnant, Arturo A Alvarez, Elizabeth T Ables
Development of multicellular organisms relies upon the coordinated regulation of cellular differentiation and proliferation. Growing evidence suggests that some molecular regulatory pathways associated with the cell cycle machinery also dictate cell fate; however, it remains largely unclear how the cell cycle is remodeled in concert with cell differentiation. During Drosophila oogenesis, mature oocytes are created through a series of precisely controlled division and differentiation steps, originating from a single tissue-specific stem cell...
July 12, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28709684/hairpin-structures-with-conserved-sequence-motifs-determine-the-3-ends-of-non-polyadenylated-invertebrate-iridovirus-transcripts
#11
İkbal Agah İnce, Gorben P Piljman, Just M Vlak, Monique M van Oers
Previously, we observed that the transcripts of Invertebrate iridescent virus 6 (IIV6) are not polyadenylated, in line with the absence of canonical poly(A) motifs (AATAAA) downstream of the open reading frames (ORFs) in the genome. Here, we determined the 3' ends of the transcripts of fifty-four IIV6 virion protein genes in infected Drosophila Schneider 2 (S2) cells. By using ligation-based amplification of cDNA ends (LACE) it was shown that the IIV6 mRNAs often ended with a CAUUA motif. In silico analysis showed that the 3'-untranslated regions of IIV6 genes have the ability to form hairpin structures (22-56 nt in length) and that for about half of all IIV6 genes these 3' sequences contained complementary TAATG and CATTA motifs...
July 11, 2017: Virology
https://www.readbyqxmd.com/read/28708826/intestinal-stem-cell-overproliferation-resulting-from-inactivation-of-the-apc-tumor-suppressor-requires-the-transcription-cofactors-earthbound-and-erect-wing
#12
Ai Tian, Hassina Benchabane, Zhenghan Wang, Chloe Zimmerman, Nan Xin, Jessica Perochon, Gabriela Kalna, Owen J Sansom, Chao Cheng, Julia B Cordero, Yashi Ahmed
Wnt/β-catenin signal transduction directs intestinal stem cell (ISC) proliferation during homeostasis. Hyperactivation of Wnt signaling initiates colorectal cancer, which most frequently results from truncation of the tumor suppressor Adenomatous polyposis coli (APC). The β-catenin-TCF transcription complex activates both the physiological expression of Wnt target genes in the normal intestinal epithelium and their aberrantly increased expression in colorectal tumors. Whether mechanistic differences in the Wnt transcription machinery drive these distinct levels of target gene activation in physiological versus pathological states remains uncertain, but is relevant for the design of new therapeutic strategies...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28707656/-regulation-of-heat-shock-gene-expression-in-response-to-stress
#13
D G Garbuz
Heat shock (HS) genes, or stress genes, code for a number of proteins that collectively form the most ancient and universal stress defense system. The system determines the cell capability of adaptation to various adverse factors and performs a variety of auxiliary functions in normal physiological conditions. Common stress factors, such as higher temperatures, hypoxia, heavy metals, and others, suppress transcription and translation for the majority of genes, while HS genes are upregulated. Transcription of HS genes is controlled by transcription factors of the HS factor (HSF) family...
May 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28706002/micrornas-that-contribute-to-coordinating-the-immune-response-in-drosophila-melanogaster
#14
Magda L Atilano, Marcus Glittenberg, Annabel Monteiro, Richard Copley, Petros Ligoxygakis
Small noncoding RNAs called microRNAs (miRNAs) have emerged as post-transcriptional regulators of gene expression related to host defences. Here, we have used Drosophila melanogaster to explore the contribution of individual or clusters of miRNAs in countering systemic C. albicans infection. From a total of 72 tested, we identify six miRNAs allelic mutant backgrounds that modulate the survival response to infection and ability to control pathogen number. These mutants also exhibit dysregulation of the Toll pathway target transcripts Drosomycin (Drs) and Immune-Induced Molecule 1 (IM1)...
July 13, 2017: Genetics
https://www.readbyqxmd.com/read/28705828/crispr-induced-null-alleles-show-that-frost-protects-drosophila-melanogaster-reproduction-after-cold-exposure
#15
Claire E Newman, Jantina Toxopeus, Hiroko Udaka, Soohyun Ahn, David M Martynowicz, Steffen P Graether, Brent J Sinclair, Anthony Percival-Smith
The ability to survive and reproduce after cold exposure is important in all kingdoms of life. However, even in a sophisticated genetic model system like Drosophila melanogaster, few genes have been identified as functioning in cold tolerance. The accumulation of the Frost (Fst) gene transcript increases after cold exposure, making it a good candidate for a gene that has a role in cold tolerance. However, despite extensive RNAi knockdown analysis, no role in cold tolerance has been assigned to Fst CRISPR is an effective technique for completely knocking down genes, and less likely to produce off-target effects than GAL4-UAS RNAi systems...
July 13, 2017: Journal of Experimental Biology
https://www.readbyqxmd.com/read/28705811/proprotein-convertase-furin1-expression-in-the-drosophila-fat-body-is-essential-for-a-normal-antimicrobial-peptide-response-and-bacterial-host-defense
#16
Saara Aittomäki, Susanna Valanne, Tapio Lehtinen, Sampsa Matikainen, Tuula A Nyman, Mika Rämet, Marko Pesu
Invading pathogens provoke robust innate immune responses in Dipteran insects, such as Drosophila melanogaster In a systemic bacterial infection, a humoral response is induced in the fat body. Gram-positive bacteria trigger the Toll signaling pathway, whereas gram-negative bacterial infections are signaled via the immune deficiency (IMD) pathway. We show here that the RNA interference-mediated silencing of Furin1-a member of the proprotein convertase enzyme family-specifically in the fat body, results in a reduction in the expression of antimicrobial peptides...
July 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28704512/a-role-for-the-drosophila-zinc-transporter-zip88e-in-protecting-against-dietary-zinc-toxicity
#17
Christopher D Richards, Coral G Warr, Richard Burke
Zinc absorption in animals is thought to be regulated in a local, cell autonomous manner with intestinal cells responding to dietary zinc content. The Drosophila zinc transporter Zip88E shows strong sequence similarity to Zips 42C.1, 42C.2 and 89B as well as mammalian Zips 1, 2 and 3, suggesting that it may act in concert with the apically-localised Drosophila zinc uptake transporters to facilitate dietary zinc absorption by importing ions into the midgut enterocytes. However, the functional characterisation of Zip88E presented here indicates that Zip88E may instead play a role in detecting and responding to zinc toxicity...
2017: PloS One
https://www.readbyqxmd.com/read/28704371/genetic-compensation-a-phenomenon-in-search-of-mechanisms
#18
REVIEW
Mohamed A El-Brolosy, Didier Y R Stainier
Several recent studies in a number of model systems including zebrafish, Arabidopsis, and mouse have revealed phenotypic differences between knockouts (i.e., mutants) and knockdowns (e.g., antisense-treated animals). These differences have been attributed to a number of reasons including off-target effects of the antisense reagents. An alternative explanation was recently proposed based on a zebrafish study reporting that genetic compensation was observed in egfl7 mutant but not knockdown animals. Dosage compensation was first reported in Drosophila in 1932, and genetic compensation in response to a gene knockout was first reported in yeast in 1969...
July 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28702320/parental-obesity-leads-to-metabolic-changes-in-the-f2-generation-in-drosophila
#19
Rebecca A S Palu, Sophia A Praggastis, Carl S Thummel
OBJECTIVE: A significant portion of the heritable risk for complex metabolic disorders cannot be attributed to classic Mendelian genetic factors. At least some of this missing heritability is thought to be due to the epigenetic influence of parental and grandparental metabolic state on offspring health. Previous work suggests that this transgenerational phenomenon is evolutionarily conserved in Drosophila. These studies, however, have all depended on dietary paradigms to alter parental metabolic state, which can have inconsistent heritable effects on the metabolism of offspring...
July 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28700947/acute-dietary-restriction-acts-via-tor-pp2a-and-myc-signaling-to-boost-innate-immunity-in-drosophila
#20
Jung-Eun Lee, Morsi Rayyan, Allison Liao, Isaac Edery, Scott D Pletcher
Dietary restriction promotes health and longevity across taxa through mechanisms that are largely unknown. Here, we show that acute yeast restriction significantly improves the ability of adult female Drosophila melanogaster to resist pathogenic bacterial infections through an immune pathway involving downregulation of target of rapamycin (TOR) signaling, which stabilizes the transcription factor Myc by increasing the steady-state level of its phosphorylated forms through decreased activity of protein phosphatase 2A...
July 11, 2017: Cell Reports
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