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Modeling gene regulation

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https://www.readbyqxmd.com/read/27926866/inflammation-induced-oxidative-stress-mediates-gene-fusion-formation-in-prostate-cancer
#1
Ram S Mani, Mohammad A Amin, Xiangyi Li, Shanker Kalyana-Sundaram, Brendan A Veeneman, Lei Wang, Aparna Ghosh, Adam Aslam, Susmita G Ramanand, Bradley J Rabquer, Wataru Kimura, Maxwell Tran, Xuhong Cao, Sameek Roychowdhury, Saravana M Dhanasekaran, Nallasivam Palanisamy, Hesham A Sadek, Payal Kapur, Alisa E Koch, Arul M Chinnaiyan
Approximately 50% of prostate cancers are associated with gene fusions of the androgen-regulated gene TMPRSS2 to the oncogenic erythroblast transformation-specific (ETS) transcription factor ERG. The three-dimensional proximity of TMPRSS2 and ERG genes, in combination with DNA breaks, facilitates the formation of TMPRSS2-ERG gene fusions. However, the origins of DNA breaks that underlie gene fusion formation in prostate cancers are far from clear. We demonstrate a role for inflammation-induced oxidative stress in the formation of DNA breaks leading to recurrent TMPRSS2-ERG gene fusions...
December 6, 2016: Cell Reports
https://www.readbyqxmd.com/read/27926822/proteomic-and-phylogenetic-coevolution-analyses-of-pm79-and-pm92-identify-interactions-with-rnapii-and-delineate-the-mcmv-late-transcription-complex
#2
Travis J Chapa, Dong Yu, Anthony R French
The regulation of the late viral gene expression in betaherpesviruses is largely undefined. We have previously shown that the murine cytomegalovirus proteins pM79 and pM92 are required for late gene transcription. Here, we provide insight into the mechanism of pM79 and pM92 activity by determining their interaction partners during infection. Co-immunoprecipitation-coupled mass spectrometry studies demonstrate that pM79 and pM92 interact with an array of cellular and viral proteins involved in transcription...
December 7, 2016: Journal of General Virology
https://www.readbyqxmd.com/read/27926536/a-minimal-titration-model-of-the-mammalian-dynamical-heat-shock-response
#3
Aude Sivéry, Emmanuel Courtade, Quentin Thommen
Environmental stress, such as oxidative or heat stress, induces the activation of the heat shock response (HSR) and leads to an increase in the heat shock proteins (HSPs) level. These HSPs act as molecular chaperones to maintain cellular proteostasis. Controlled by highly intricate regulatory mechanisms, having stress-induced activation and feedback regulations with multiple partners, the HSR is still incompletely understood. In this context, we propose a minimal molecular model for the gene regulatory network of the HSR that reproduces quantitatively different heat shock experiments both on heat shock factor 1 (HSF1) and HSPs activities...
December 7, 2016: Physical Biology
https://www.readbyqxmd.com/read/27925611/differential-expression-of-bcl-2-in-the-cochlea-and-auditory-cortex-of-a-mouse-model-of-age-related-hearing-loss
#4
Qiuhong Huang, Hao Xiong, Haidi Yang, Yongkang Ou, Zhigang Zhang, Suijun Chen, Yongyi Ye, Yiqing Zheng
Bcl-2, the first gene shown to be involved in apoptosis, is a potent regulator of cell survival and known to have protective effects against a variety of age-related diseases. However, the possible relationship between hearing and Bcl-2 expression in the cochlea or auditory cortex of C57BL/6 mice, a mouse model of age-related hearing loss, is still unknown. Using RT-PCR, immunohistochemistry, and Western blot analysis, our results show that Bcl-2 is strongly expressed in the inner hair cells and spiral ganglion neurons of young mice...
December 8, 2016: Audiology & Neuro-otology
https://www.readbyqxmd.com/read/27924858/transcriptomic-characterization-and-curation-of-candidate-neuropeptides-regulating-reproduction-in-the-eyestalk-ganglia-of-the-australian-crayfish-cherax-quadricarinatus
#5
Tuan Viet Nguyen, Scott F Cummins, Abigail Elizur, Tomer Ventura
The Australian redclaw crayfish (Cherax quadricarinatus) has recently received attention as an emerging candidate for sustainable aquaculture production in Australia and worldwide. More importantly, C. quadricarinatus serves as a good model organism for the commercially important group of decapod crustaceans as it is distributed worldwide, easy to maintain in the laboratory and its reproductive cycle has been well documented. In order to better understand the key reproduction and development regulating mechanisms in decapod crustaceans, the molecular toolkit available for model organisms such as C...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924824/short-day-length-induced-decrease-of-cesium-uptake-without-altering-potassium-uptake-manner-in-poplar
#6
Yusaku Noda, Jun Furukawa, Tsutomu Aohara, Naoto Nihei, Atsushi Hirose, Keitaro Tanoi, Tomoko M Nakanishi, Shinobu Satoh
Short day length-induced alteration of potassium (K) localization in perennial trees is believed to be a mechanism for surviving and adapting to severe winters. To investigate the relationship between cesium (Cs) and K localizations, a model tree poplar, hybrid aspen T89, was employed. Under short day length conditions, the amount of (137)Cs absorbed through the root and translocated to the root was drastically reduced, but (42)K was not. Potassium uptake from the rhizosphere is mediated mainly by KUP/HAK/KT and CNGC transporters...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27924729/conjugated-linoleic-acid-isomers-exert-differential-effects-on-an-adipocyte-model-of-hiv-associated-lipodystrophy
#7
Cathríona R Loonam, Sandra D O Dell, Anne Mullen
BACKGROUND: HIV-associated lipodystrophy is associated with decreased expression of PPAR-γ in adipose tissue. Conjugated linoleic acid (CLA) isomers (cis9, trans11 and trans10, cis12) are putative PPAR-γ agonists, but have not previously been investigated in the context of HIV-associated lipodystrophy. METHODS: 3T3-L1 pre-adipocytes were differentiated in the presence of ritonavir (20 μM as per previous experimental models) and 100 μM cis9,trans11, trans10,cis12 or vehicle control, DMSO...
December 7, 2016: Current HIV Research
https://www.readbyqxmd.com/read/27924588/antioxidant-micronutrients-and-oxidative-stress-biomarkers
#8
Iain L C Chapple, Helen R Griffiths, Mike R Milward, Martin R Ling, Melissa M Grant
Chronic inflammatory diseases are the major causes of mortality in humans and recent research has improved our understanding of the major impact of life-style factors upon inflammatory diseases and conditions. One of the most influential of these is nutrition, which may drive both pro-inflammatory as well as anti-inflammatory cascades at molecular and cellular levels. There are a variety of model systems that may be employed to investigate the impact of micronutrients and macronutrients upon inflammatory pathways, many of which operate through oxidative stress, either at the level of controlling the redox state of the cell and downstream redox-regulated gene transcription factors, and other acting as free radical generating or scavenging agents...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924577/analyzing-perk-activation-during-planarian-regeneration
#9
Susanna Fraguas, Yoshihiko Umesono, Kiyokazu Agata, Francesc Cebrià
Planarians are an ideal model in which to study stem cell-based regeneration. After amputation, planarian pluripotent stem cells surrounding the wound proliferate to produce the regenerative blastema, in which they differentiate into the missing tissues and structures. Recent independent studies in planarians have shown that Smed-egfr-3, a gene encoding a homologue of epidermal growth factor (EGF) receptors, and DjerkA, which encodes an extracellular signal-regulated kinase (ERK), may control cell differentiation and blastema growth...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924572/isolation-of-mouse-embryonic-stem-cell-lines-in-the-study-of-erk1-2-map-kinase-signaling
#10
Marc K Saba-El-Leil, Christophe Frémin, Sylvain Meloche
Mouse embryonic stem (ES) cells have proven to be invaluable research tools for dissecting the role of signaling pathways in embryonic development, adult physiology, and various diseases. ES cells are amenable to genetic manipulation by classical gene targeting via homologous recombination or by genome editing technologies. These cells can be used to generate genetically modified mouse models or to study the signaling circuitry regulating self-renewal and early lineage commitment. In this chapter, we describe methods used for the isolation and establishment of mouse ES cell lines from blastocyst embryos and for the measurement of ERK1/2 activity in ES cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924488/elucidating-mechanisms-of-molecular-recognition-between-human-argonaute-and-mirna-using-computational-approaches
#11
Hanlun Jiang, Lizhe Zhu, Amélie Héliou, Xin Gao, Julie Bernauer, Xuhui Huang
MicroRNA (miRNA) and Argonaute (AGO) protein together form the RNA-induced silencing complex (RISC) that plays an essential role in the regulation of gene expression. Elucidating the underlying mechanism of AGO-miRNA recognition is thus of great importance not only for the in-depth understanding of miRNA function but also for inspiring new drugs targeting miRNAs. In this chapter we introduce a combined computational approach of molecular dynamics (MD) simulations, Markov state models (MSMs), and protein-RNA docking to investigate AGO-miRNA recognition...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27924158/lycorine-downregulates-hmgb1-to-inhibit-autophagy-and-enhances-bortezomib-activity-in-multiple-myeloma
#12
Mridul Roy, Long Liang, Xiaojuan Xiao, Yuanliang Peng, Yuhao Luo, Weihua Zhou, Ji Zhang, Lugui Qiu, Shuaishuai Zhang, Feng Liu, Mao Ye, Wen Zhou, Jing Liu
Multiple myeloma (MM) is largely incurable and drug-resistant. Novel therapeutic approaches such as inhibiting autophagy or rational drug combinations are aimed to overcome this issue. In this study, we found that lycorine exhibits a promising anti-proliferative activity against MM in vitro and in vivo by inhibiting autophagy. We identified High mobility group box 1 (HMGB1), an important regulator of autophagy, as the most aberrantly expressed protein after lycorine treatment and as a critical mediator of lycorine activity...
2016: Theranostics
https://www.readbyqxmd.com/read/27924077/metabolic-regulation-of-gene-expression-through-histone-acylations
#13
Benjamin R Sabari, Di Zhang, C David Allis, Yingming Zhao
Eight types of short-chain Lys acylations have recently been identified on histones: propionylation, butyrylation, 2-hydroxyisobutyrylation, succinylation, malonylation, glutarylation, crotonylation and β-hydroxybutyrylation. Emerging evidence suggests that these histone modifications affect gene expression and are structurally and functionally different from the widely studied histone Lys acetylation. In this Review, we discuss the regulation of non-acetyl histone acylation by enzymatic and metabolic mechanisms, the acylation 'reader' proteins that mediate the effects of different acylations and their physiological functions, which include signal-dependent gene activation, spermatogenesis, tissue injury and metabolic stress...
December 7, 2016: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/27924068/protein-inhibitor-of-activated-stat-4-pias4-regulates-liver-fibrosis-through-modulating-smad3-activity
#14
Huihui Xu, Zhiwen Fan, Wenfang Tian, Yong Xu
Excessive fibrogenesis disrupts normal liver structure, impairs liver function, and precipitates the development of cirrhosis, an irreversible end-stage liver disease. A host of factors including nutrition surplus contribute to liver fibrosis but the underlying mechanism is not fully understood. In the present study, we investigated the involvement of protein inhibitor for activated stat 4 (PIAS4) in liver fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH). We report that PIAS4 silencing using short hairpin RNA (shRNA) attenuated high-fat high-carbohydrate (HFHC) diet induced liver fibrosis in mice...
November 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/27924044/plamom-a-comprehensive-database-compiles-plant-mobile-macromolecules
#15
Daogang Guan, Bin Yan, Christoph Thieme, Jingmin Hua, Hailong Zhu, Kenneth R Boheler, Zhongying Zhao, Friedrich Kragler, Yiji Xia, Shoudong Zhang
In plants, various phloem-mobile macromolecules including noncoding RNAs, mRNAs and proteins are suggested to act as important long-distance signals in regulating crucial physiological and morphological transition processes such as flowering, plant growth and stress responses. Given recent advances in high-throughput sequencing technologies, numerous mobile macromolecules have been identified in diverse plant species from different plant families. However, most of the identified mobile macromolecules are not annotated in current versions of species-specific databases and are only available as non-searchable datasheets...
October 24, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27923956/adaptation-to-potassium-limitation-is-essential-for-acinetobacter-baumannii-pneumonia-pathogenesis
#16
Reham Samir, Salma H Hussein, Noha M Elhosseiny, Marwa S Khattab, Alaa E Shawky, Ahmed S Attia
BACKGROUND:  Acinetobacter baumannii is challenging the healthcare community as the cause of a wide range of untreatable infections. New targets need to be explored for the development of therapeutics. METHODS:  The potassium-dependent protein (Kdp) system was investigated via bioinformatics and genetic tools. An isogenic mutant was constructed in kdpE and complemented in trans Gene expression and the ability to grow under potassium-limited conditions were investigated...
December 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27923835/rb-loss-promotes-prostate-cancer-metastasis
#17
Chellappagounder Thangavel, Ettickan Boopathi, Yi Liu, Alex Haber, Adam Ertel, Anshul Bhardwaj, Sankar Addya, Noelle Williams, Steve Ciment, Paolo Cotzia, Jeffry L Dean, Adam E Snook, Chris McNair, Matthew A Price, James R Hernandez, Shuang G Zhao, Ruth Birbe, James B McCarthy, Eva A Turely, Kenneth J Pienta, Felix Y Feng, Adam P Dicker, Karen E Knudsen, Robert B Den
RB loss occurs commonly in neoplasia but its contributions to advanced cancer have not been assessed directly. Here we show that RB loss in multiple murine models of cancer produces a pro-metastatic phenotype. Gene expression analyses showed that regulation of the cell motility receptor RHAMM by the RB/E2F pathway was critical for epithelia-mesenchyme translation, motility and invasion by cancer cells. Genetic modulation or pharmacological inhibition of RHAMM activity was sufficient and necessary for metastatic phenotypes induced by RB loss in prostate cancer...
December 6, 2016: Cancer Research
https://www.readbyqxmd.com/read/27923776/establishment-of-expression-in-the-shortroot-scarecrow-transcriptional-cascade-through-opposing-activities-of-both-activators-and-repressors
#18
Erin E Sparks, Colleen Drapek, Allison Gaudinier, Song Li, Mitra Ansariola, Ning Shen, Jessica H Hennacy, Jingyuan Zhang, Gina Turco, Jalean J Petricka, Jessica Foret, Alexander J Hartemink, Raluca Gordân, Molly Megraw, Siobhan M Brady, Philip N Benfey
Tissue-specific gene expression is often thought to arise from spatially restricted transcriptional cascades. However, it is unclear how expression is established at the top of these cascades in the absence of pre-existing specificity. We generated a transcriptional network to explore how transcription factor expression is established in the Arabidopsis thaliana root ground tissue. Regulators of the SHORTROOT-SCARECROW transcriptional cascade were validated in planta. At the top of this cascade, we identified both activators and repressors of SHORTROOT...
December 5, 2016: Developmental Cell
https://www.readbyqxmd.com/read/27923712/regulation-of-microrna-1-mir-1-expression-in-human-cancer
#19
REVIEW
Chao Han, Jacson K Shen, Francis J Hornicek, Quancheng Kan, Zhenfeng Duan
MicroRNAs (miRs) have been found to play important roles in tumorigenesis, apoptosis, metastasis, and drug resistance in cancer. Among a number of miRs, miR-1 was shown to be predominantly downregulated in almost all examined human cancers. As a tumor suppressor miR involved in post-transcriptional regulation of crucial tumor associated gene expression, miR-1 represents a promising target for anticancer therapy. Re-expression of miR-1 can suppress cancer cell proliferation, promote apoptosis, and reverse drug resistance in cancers both in vitro and in vivo...
December 3, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27923658/temporal-regulation-of-gap-junctional-communication-between-tenocytes-subjected-to-static-tensile-strain-with-physiological-and-non-physiological-amplitudes
#20
Eijiro Maeda, Haicheng Pian, Toshiro Ohashi
The present study has been performed on temporal changes in gap junctional intercellular communication (GJIC) between tenocytes under static tensile strain with the magnitude of 0% (no strain), 4% (physiological magnitude) or 8% (overloading magnitude) during a 24-h culture period. Tenocytes were isolated from rabbit Achilles tendon and seeded on a stretchable microgroove substrate. GJIC was evaluated as intercellular diffusion coefficient of calcein (DGJ) using fluorescence loss in photobleaching (FLIP) protocol accompanied with a mathematical model of molecular diffusion both within the cell and between the cells...
December 3, 2016: Biochemical and Biophysical Research Communications
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