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https://www.readbyqxmd.com/read/28318367/combinatorial-control-of-messenger-rnas-by-pumilio-nanos-and-brain-tumor-proteins
#1
René M Arvola, Chase A Weidmann, Traci M Tanaka Hall, Aaron C Goldstrohm
Eukaryotes possess a vast array of RNA-binding proteins (RBPs) that affect mRNAs in diverse ways to control protein expression. Combinatorial regulation of mRNAs by RBPs is emerging as the rule. No example illustrates this as vividly as the partnership of three Drosophila RBPs, Pumilio, Nanos and Brain Tumor, which have overlapping functions in development, stem cell maintenance and differentiation, fertility and neurological processes. Here we synthesize thirty years of research with new insights into their molecular functions and mechanisms of action...
March 20, 2017: RNA Biology
https://www.readbyqxmd.com/read/28316031/transactivation-domain-of-human-c-myc-is-essential-to-alleviate-poly-q-mediated-neurotoxicity-in-drosophila-disease-models
#2
Kritika Raj, Surajit Sarkar
Polyglutamine (poly(Q)) disorders, such as Huntington's disease (HD) and spinocerebellar ataxias, represent a group of neurological disorders which arise due to an atypically expanded poly(Q) tract in the coding region of the affected gene. Pathogenesis of these disorders inside the cells begins with the assembly of these mutant proteins in the form of insoluble inclusion bodies (IBs), which progressively sequester several vital cellular transcription factors and other essential proteins, and finally leads to neuronal dysfunction and apoptosis...
March 18, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28315838/germline-proliferation-is-regulated-by-somatic-endocytic-genes-via-jnk-and-bmp-signaling-in-drosophila
#3
Yaning Tang, Qing Geng, Di Chen, Shaowei Zhao, Xian Liu, Zhaohui Wang
Signals derived from the microenvironment contribute greatly to tumorigenesis. The underlying mechanism requires thorough investigation. Here, we use Drosophila testis as a model system to address this question, taking the advantage of the ease to distinguish germline and somatic cells and to track the cell numbers. In an EMS mutagenesis screen, we identified Rab5, a key factor in endocytosis, for its non-autonomous role in germline proliferation. The disruption of Rab5 in somatic cyst cells, which escort the development of germline lineage, induced the over-proliferation of under-differentiated but genetically wild-type germ cells...
March 17, 2017: Genetics
https://www.readbyqxmd.com/read/28304334/kdm2-family-members-are-regulated-by-hif-1-in-hypoxia
#4
Michael Batie, Jimena Druker, Laura D'Ignazio, Sonia Rocha
Hypoxia is not only a developmental cue but also a stress and pathological stimulus in many human diseases. The response to hypoxia at the cellular level relies on the activity of the transcription factor family, hypoxia inducible factor (HIF). HIF-1 is responsible for the acute response and transactivates a variety of genes involved in cellular metabolism, cell death, and cell growth. Here, we show that hypoxia results in increased mRNA levels for human lysine (K)-specific demethylase 2 (KDM2) family members, KDM2A and KDM2B, and also for Drosophila melanogaster KDM2, a histone and protein demethylase...
March 17, 2017: Cells
https://www.readbyqxmd.com/read/28302795/causal-role-for-inheritance-of-h3k27me3-in-maintaining-the-off-state-of-a-drosophila-hox-gene
#5
Rory T Coleman, Gary Struhl
Many eukaryotic cells can respond to transient environmental or developmental stimuli with heritable changes in gene expression that are associated with nucleosome modifications. However, it remains uncertain whether modified nucleosomes play a causal role in transmitting such epigenetic memories, as opposed to controlling or merely reflecting transcriptional states inherited by other means. Here, we provide in vivo evidence that H3K27 trimethylated nucleosomes, once established at a repressed Drosophila HOX gene, remain heritably associated with that gene and can carry the memory of the silenced state through multiple rounds of replication, even when the capacity to copy the H3K27me3 mark to newly incorporated nucleosomes is diminished or abolished...
March 16, 2017: Science
https://www.readbyqxmd.com/read/28302666/mtorc1-signalling-mediates-pi3k-dependent-large-lipid-droplet-accumulation-in-drosophila-ovarian-nurse-cells
#6
Lawrence B Mensah, Deborah C I Goberdhan, Clive Wilson
Insulin and insulin-like growth factor signalling (IIS), which is primarily mediated by the PI3-kinase (PI3K)/PTEN/Akt kinase signalling cassette, is a highly evolutionary conserved pathway involved in co-ordinating growth, development, ageing and nutrient homeostasis with dietary intake. It controls transcriptional regulators, in addition to promoting signalling by mechanistic Target of Rapamycin (mTOR) Complex 1 (mTORC1), which stimulates biosynthesis of proteins and other macromolecules, and drives organismal growth...
March 16, 2017: Biology Open
https://www.readbyqxmd.com/read/28301478/retrotransposon-activation-contributes-to-neurodegeneration-in-a-drosophila-tdp-43-model-of-als
#7
Lisa Krug, Nabanita Chatterjee, Rebeca Borges-Monroy, Stephen Hearn, Wen-Wei Liao, Kathleen Morrill, Lisa Prazak, Nikolay Rozhkov, Delphine Theodorou, Molly Hammell, Josh Dubnau
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two incurable neurodegenerative disorders that exist on a symptomological spectrum and share both genetic underpinnings and pathophysiological hallmarks. Functional abnormality of TAR DNA-binding protein 43 (TDP-43), an aggregation-prone RNA and DNA binding protein, is observed in the vast majority of both familial and sporadic ALS cases and in ~40% of FTLD cases, but the cascade of events leading to cell death are not understood...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28301294/fubp-kh-domain-proteins-in-transcription-back-to-the-future
#8
Leonie M Quinn
Drosophila genetic studies demonstrate that cell and tissue growth regulation is a primary developmental function of P-element somatic inhibitor (Psi), the sole ortholog of FUBP family RNA/DNA-binding proteins. Psi achieves growth control through interaction with Mediator, observations that should put to rest controversy surrounding Pol II transcriptional functions for these KH domain proteins.
February 16, 2017: Transcription
https://www.readbyqxmd.com/read/28299673/roles-of-runx-in-hypoxia-induced-responses-and-angiogenesis
#9
Sun Hee Lee, Sarala Manandhar, You Mie Lee
During the past two decades, Runt domain transcription factors (RUNX1, 2, and 3) have been investigated in regard to their function, structural elements, genetic variants, and roles in normal development and pathological conditions. The Runt family proteins are evolutionarily conserved from Drosophila to mammals, emphasizing their physiological importance. A hypoxic microenvironment caused by insufficient blood supply is frequently observed in developing organs, growing tumors, and tissues that become ischemic due to impairment or blockage of blood vessels...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28299188/genome-wide-measurement-of-spatial-expression-in-patterning-mutants-of-drosophila-melanogaster
#10
Peter A Combs, Michael B Eisen
Patterning in the Drosophila melanogaster embryo is affected by multiple maternal factors, but the effect of these factors on spatial gene expression has not been systematically analyzed. Here we characterize the effect of the maternal factors Zelda, Hunchback and Bicoid by cryosectioning wildtype and mutant blastoderm stage embryos and sequencing mRNA from each slice. The resulting atlas of spatial gene expression highlights the intersecting roles of these factors in regulating spatial patterns, and serves as a resource for researchers studying spatial patterning in the early embryo...
2017: F1000Research
https://www.readbyqxmd.com/read/28298298/non-reciprocal-homeostatic-compensation-in-drosophila-potassium-channel-mutants
#11
Eugene Z Kim, Julie Vienne, Michael Rosbash, Leslie C Griffith
Homeostatic control of intrinsic excitability is important for long-term regulation of neuronal activity. In conjunction with many other forms of plasticity, intrinsic homeostasis helps neurons maintain stable activity regimes in the face of external input variability and destabilizing genetic mutations. In this study, we report a mechanism by which Drosophila melanogaster larval motor neurons stabilize hyperactivity induced by the loss of the delayed rectifying K(+) channel Shaker Cognate B (Shab), by upregulating the Ca(2+)-dependent K(+) channel encoded by the slowpoke (slo) gene...
March 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28296634/constitutive-scaffolding-of-multiple-wnt-enhanceosome-components-by-legless-bcl9
#12
Laurens M van Tienen, Juliusz Mieszczanek, Marc Fiedler, Trevor J Rutherford, Mariann Bienz
Wnt/β-catenin signaling elicits context-dependent transcription switches that determine normal development and oncogenesis. These are mediated by the Wnt enhanceosome, a multiprotein complex binding to the Pygo chromatin reader and acting through TCF/LEF-responsive enhancers. Pygo renders this complex Wnt-responsive, by capturing β-catenin via the Legless/BCL9 adaptor. We used CRISPR/Cas9 genome engineering of Drosophila legless (lgs) and human BCL9 and B9L to show that the C-terminus downstream of their adaptor elements is crucial for Wnt responses...
March 15, 2017: ELife
https://www.readbyqxmd.com/read/28296185/chip-ldb1-interacts-with-tailup-islet1-to-regulate-cardiac-gene-expression-in-drosophila
#13
Kathrin Werner, Cornelia Donow, Petra Pandur
The LIM-homeodomain transcription factor Tailup (Tup) is a component of the complex cardiac transcriptional network governing specification and differentiation of cardiac cells in Drosophila. LIM-domain containing factors are known to interact with the adaptor molecule Chip/Ldb1 to form higher order protein complexes to regulate gene expression thereby determining a cell's developmental fate. However, with respect to Drosophila heart development, it has not been investigated yet, whether Chip and tup interact to regulate the generation of different cardiac cell types...
March 15, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28289197/toll-pathway-is-required-for-wound-induced-expression-of-barrier-repair-genes-in-the-drosophila-epidermis
#14
Amalia Capilla, Dmitry Karachentsev, Rachel A Patterson, Anita Hermann, Michelle T Juarez, William McGinnis
The epidermis serves as a protective barrier in animals. After epidermal injury, barrier repair requires activation of many wound response genes in epidermal cells surrounding wound sites. Two such genes in Drosophila encode the enzymes dopa decarboxylase (Ddc) and tyrosine hydroxylase (ple). In this paper we explore the involvement of the Toll/NF-κB pathway in the localized activation of wound repair genes around epidermal breaks. Robust activation of wound-induced transcription from ple and Ddc requires Toll pathway components ranging from the extracellular ligand Spätzle to the Dif transcription factor...
March 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28285992/tissue-wide-mechanical-forces-influence-the-polarity-of-stomatal-stem-cells-in-arabidopsis
#15
Martin Bringmann, Dominique C Bergmann
Mechanical information is an important contributor to cell polarity in uni- and multicellular systems [1-3]. In planar tissues like the Drosophila wing, cell polarity reorients during growth as cells divide and reorganize [4]. In another planar tissue, the Arabidopsis leaf epidermis [5], polarized, asymmetric divisions of stomatal stem cells (meristemoid mother cells [MMCs]) are fundamental for the generation and patterning of multiple cell types, including stomata. The activity of key transcription factors, polarizing factors [6], and peptide signals [7] explains some local stomatal patterns emerging from the behavior of a few lineally related cells [6, 8-11]...
March 20, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28282436/regions-of-very-low-h3k27me3-partition-the-drosophila-genome-into-topological-domains
#16
Sherif El-Sharnouby, Bettina Fischer, Jose Paolo Magbanua, Benjamin Umans, Rosalyn Flower, Siew Woh Choo, Steven Russell, Robert White
It is now well established that eukaryote genomes have a common architectural organization into topologically associated domains (TADs) and evidence is accumulating that this organization plays an important role in gene regulation. However, the mechanisms that partition the genome into TADs and the nature of domain boundaries are still poorly understood. We have investigated boundary regions in the Drosophila genome and find that they can be identified as domains of very low H3K27me3. The genome-wide H3K27me3 profile partitions into two states; very low H3K27me3 identifies Depleted (D) domains that contain housekeeping genes and their regulators such as the histone acetyltransferase-containing NSL complex, whereas domains containing moderate-to-high levels of H3K27me3 (Enriched or E domains) are associated with regulated genes, irrespective of whether they are active or inactive...
2017: PloS One
https://www.readbyqxmd.com/read/28280330/zinc-oxide-nanoparticles-exhibit-cytotoxicity-and-genotoxicity-through-oxidative-stress-responses-in-human-lung-fibroblasts-and-drosophila-melanogaster
#17
Cheng Teng Ng, Liang Qing Yong, Manoor Prakash Hande, Choon Nam Ong, Liya E Yu, Boon Huat Bay, Gyeong Hun Baeg
BACKGROUND: Although zinc oxide nanoparticles (ZnO NPs) have been widely used, there has been an increasing number of reports on the toxicity of ZnO NPs. However, study on the underlying mechanisms under in vivo conditions is insufficient. METHODS: In this study, we investigated the toxicological profiles of ZnO NPs in MRC5 human lung fibroblasts in vitro and in an in vivo model using the fruit fly Drosophila melanogaster. A comprehensive study was conducted to evaluate the uptake, cytotoxicity, reactive oxygen species (ROS) formation, gene expression profiling and genotoxicity induced by ZnO NPs...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28278156/a-new-mode-of-dna-binding-distinguishes-capicua-from-other-hmg-box-factors-and-explains-its-mutation-patterns-in-cancer
#18
Marta Forés, Lucía Simón-Carrasco, Leiore Ajuria, Núria Samper, Sergio González-Crespo, Matthias Drosten, Mariano Barbacid, Gerardo Jiménez
HMG-box proteins, including Sox/SRY (Sox) and TCF/LEF1 (TCF) family members, bind DNA via their HMG-box. This binding, however, is relatively weak and both Sox and TCF factors employ distinct mechanisms for enhancing their affinity and specificity for DNA. Here we report that Capicua (CIC), an HMG-box transcriptional repressor involved in Ras/MAPK signaling and cancer progression, employs an additional distinct mode of DNA binding that enables selective recognition of its targets. We find that, contrary to previous assumptions, the HMG-box of CIC does not bind DNA alone but instead requires a distant motif (referred to as C1) present at the C-terminus of all CIC proteins...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28276426/microrna-92a-is-a-circadian-modulator-of-neuronal-excitability-in-drosophila
#19
Xiao Chen, Michael Rosbash
Many biological and behavioural processes of animals are governed by an endogenous circadian clock, which is dependent on transcriptional regulation. Here we address post-transcriptional regulation and the role of miRNAs in Drosophila circadian rhythms. At least six miRNAs show cycling expression levels within the pigment dispersing factor (PDF) cell-pacemaker neurons; only mir-92a peaks during the night. In vivo calcium monitoring, dynamics of PDF projections, ArcLight, GCaMP6 imaging and sleep assays indicate that mir-92a suppresses neuronal excitability...
March 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28275687/hedgehog-signaling-links-chronic-inflammation-to-gastric-cancer-precursor-lesions
#20
REVIEW
Juanita L Merchant, Lin Ding
Since its initial discovery in Drosophila, Hedgehog (HH) signaling has long been associated with foregut development. The mammalian genome expresses 3 HH ligands, with sonic hedgehog (SHH) levels highest in the mucosa of the embryonic foregut. More recently, interest in the pathway has shifted to improving our understanding of its role in gastrointestinal cancers. The use of reporter mice proved instrumental in our ability to probe the expression pattern of SHH ligand and the cell types responding to canonical HH signaling during homeostasis, inflammation, and neoplastic transformation...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
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