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Gene regulatory networks

Jeganathan Manivannan, Manjunath Prashanth, Venkatesan Saravana Kumar, Manickaraj Shairam, Jayachandran Subburaj
Since there is no precise therapy for treating vascular calcification by directly targeting the vascular wall, we aim to unveil novel drug targets through mining the molecular effect of a high phosphate environment on vascular cells through computational methods. Here, we hypothesize that manipulation of the vascular pathogenic network by small molecule therapeutics predicted from prior knowledge might offer great promise. With this, we intend to understand the publicly available transcriptomic data of vascular smooth muscle cells and endothelial cells exposed to the high phosphate induced vascular calcification milieu and to re-examine the above published experiments for reasons different from those examined in the previous studies through multilevel systems biological understanding...
October 18, 2016: Molecular BioSystems
Federica Parodi, Roberta Carosio, Marco Ragusa, Cinzia Di Pietro, Marco Maugeri, Davide Barbagallo, Fabio Sallustio, Giorgio Allemanni, Maria Pia Pistillo, Ida Casciano, Alessandra Forlani, Francesco P Schena, Michele Purrello, Massimo Romani, Barbara Banelli
In neuroblastoma, the epigenetic landscape is more profoundly altered in aggressive compared to lower grade tumors and the concomitant hypermethylation of many genes, defined as "methylator phenotype", has been associated with poor outcome. DNA methylation can interfere with gene expression acting at distance through the methylation or demethylation of the regulatory regions of miRNAs. The multiplicity of miRNA targets may result in the simultaneous alteration of many biological pathways like cell proliferation, apoptosis, migration and differentiation...
October 14, 2016: Biochimica et Biophysica Acta
Shanshan Xu, Lanlan Dong, Yingying Shi, Liujun Chen, Peipei Yuan, Shuang Wang, Zhi Li, Yan Sun, Song Han, Jun Yin, Biwen Peng, Xiaohua He, Wanhong Liu
Human foamy virus (HFV) is a complex and unique retrovirus with the longest genomes among retroviruses used as vectors for gene therapy. Long non-coding RNAs (lncRNAs) are regarded as key regulators that involved in diverse biological processes during viral infection. However, the role of lncRNAs in HFV infection remains unknown. In this study, we utilized next-generation sequencing to first characterize lncRNAs in 293T cells after HFV infection, evaluating length distribution, exon number distribution, volcano picture and lncRNA class distribution...
October 18, 2016: AIDS Research and Human Retroviruses
Steven J Burgess, Ignasi Granero-Moya, Mathieu J Grangé-Guermente, Chris Boursnell, Matthew J Terry, Julian M Hibberd
C4 photosynthesis acts as a carbon concentrating mechanism that leads to large increases in photosynthetic efficiency. The C4 pathway is found in more than 60 plant lineages(1) but the molecular enablers of this evolution are poorly understood. In particular, it is unclear how non-photosynthetic proteins in the ancestral C3 system have repeatedly become strongly expressed and integrated into photosynthesis gene regulatory networks in C4 leaves. Here, we provide clear evidence that in C3 leaves, genes encoding key enzymes of the C4 pathway are already co-regulated with photosynthesis genes and are controlled by both light and chloroplast-to-nucleus signalling...
October 17, 2016: Nature Plants
Paulina Płoszaj, Andrzej Regiec, Stanisław Ryng, Agnieszka Piwowar, Marian L Kruzel
The 5-amino-3-methyl-4-isoxazolecarboxylic acid hydrazide (HIX) is a synthetic isoxazole derivative with a potential for development as an anti-inflammatory drug candidate. The goal of this study was to explore in vitro autoimmune and inflammatory gene modulation by HIX in human Caco-2 cultured cells. The effect of low dose of HIX was tested on the expression level of RNA in 24h Caco-2 cultures using the QIAGEN Th17 for Autoimmunity & Inflammation RT(2) Profiler PCR Array. We choose the PCR technology as the most reliable and sensitive gene expression profiling method for analyzing specific gene regulatory networks...
October 17, 2016: Immunopharmacology and Immunotoxicology
Jing-Yi Li, Li-Li Zheng, Ting-Ting Wang, Min Hu
BACKGROUND: Melanoma is a type of cancer that develops from the pigment-containing cells. Until now, its pathological mechanisms remain largely unknown. The aim of this study was to identify metastasis-related microRNA (miRNAs) and gain an understanding of the biological functions in the metastasis of melanoma. METHODS: We searched the PubMed and Gene Expression Omnibus database to collect miRNA expression profiling datasets about melanoma, with key words of "melanoma", "miRNA", "microarray", and "gene expression profiling"...
2016: Chinese Medical Journal
John G Conboy
The Rbfox genes encode an ancient family of sequence-specific RNA binding proteins (RBPs) that are critical developmental regulators in multiple tissues including skeletal muscle, cardiac muscle, and brain. The hallmark of Rbfox proteins is a single high-affinity RRM domain, highly conserved from insects to humans, that binds preferentially to UGCAUG motifs at diverse regulatory sites in pre-mRNA introns, mRNA 3'UTRs, and pre-miRNAs hairpin structures. Versatile regulatory circuits operate on Rbfox pre-mRNA and mRNA to ensure proper expression of Rbfox1 protein isoforms, which then act on the broader transcriptome to regulate alternative splicing networks, mRNA stability and translation, and microRNA processing...
October 17, 2016: Wiley Interdisciplinary Reviews. RNA
Jingxue Wang, Sanjay K Singh, Chunfang Du, Chen Li, Jianchun Fan, Sitakanta Pattanaik, Ling Yuan
Rapeseed (Brassica napus) is an important oil seed crop, providing more than 13% of the world's supply of edible oils. An in-depth knowledge of the gene network involved in biosynthesis and accumulation of seed oil is critical for the improvement of B. napus. Using available genomic and transcriptomic resources, we identified 1,750 acyl-lipid metabolism (ALM) genes that are distributed over 19 chromosomes in the B. napus genome. B. rapa and B. oleracea, two diploid progenitors of B. napus, contributed almost equally to the ALM genes...
2016: Frontiers in Plant Science
Ke Huang, Jiao Gao, Juan Du, Ning Ma, Yanling Zhu, Pengfei Wu, Tian Zhang, Wenqian Wang, Yuhang Li, Qianyu Chen, Andrew Paul Hutchins, Zhongzhou Yang, Yi Zheng, Jian Zhang, Yongli Shan, Xuejia Li, Baojian Liao, Jiajun Liu, Jinyong Wang, Bing Liu, Guangjin Pan
The transition from hemogenic endothelial cells (HECs) to hematopoietic stem/progenitor cells (HS/PCs), or endothelial to hematopoietic transition (EHT), is a critical step during hematopoiesis. However, little is known about the molecular determinants of HECs due to the challenge in defining HECs. We report here the generation of GATA2(w/eGFP) reporter in human embryonic stem cells (hESCs) to mark cells expressing GATA2, a critical gene for EHT. We show that during differentiation, functional HECs are almost exclusively GATA2/eGFP(+)...
October 12, 2016: Stem Cell Reports
Yuejuan Cao, Rongqing Li, Yangchun Li, Tao Zhang, Nan Wu, Jianyan Zhang, Zhaozeng Guo
BACKGROUND: Acute myocardial infarction (AMI) is a common disease with serious mortality and morbidity, worldwide. The present study aimed to identify differentially expressed genes (DEGs) and construct a transcription factor-gene regulatory network to further study the early diagnosis of AMI. METHODS: The integrated analysis of publicly available Gene Expression Omnibus datasets of AMI was performed. Differentially expressed genes were identified between AMI and normal blood samples...
July 26, 2016: Heart, Lung & Circulation
Juan Xu, ZiShan Wang, Shengli Li, Juan Chen, Jinwen Zhang, Chunjie Jiang, Zheng Zhao, Jing Li, Yongsheng Li, Xia Li
Although systematic genomic studies have identified a broad spectrum of non-coding RNAs (ncRNAs) that are involved in breast cancer, our understanding of the epigenetic dysregulation of those ncRNAs remains limited. Here, we systematically analysed the epigenetic alterations of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in two breast cancer subtypes (luminal and basal). Widespread epigenetic alterations of miRNAs and lncRNAs were observed in both cancer subtypes. In contrast to protein-coding genes, the majority of epigenetically dysregulated ncRNAs were shared between subtypes, but a subset of transcriptomic and corresponding epigenetic changes occurred in a subtype-specific manner...
October 14, 2016: Briefings in Bioinformatics
P Zhang, L Tao, X Zeng, C Qin, S Y Chen, F Zhu, S Y Yang, Z R Li, W P Chen, Y Z Chen
The studies of biological, disease and pharmacological networks are facilitated by the systems-level investigations using computational tools. In particular, the network descriptors developed in other disciplines have found increasing applications in the study of the protein, gene regulatory, metabolic, disease, and drug-targeted networks. Facilities are provided by the public web-servers for computing network descriptors, but many descriptors are not covered including those used or useful for biological studies...
October 11, 2016: Journal of Molecular Biology
Trey K Sato, Mary Tremaine, Lucas S Parreiras, Alexander S Hebert, Kevin S Myers, Alan J Higbee, Maria Sardi, Sean J McIlwain, Irene M Ong, Rebecca J Breuer, Ragothaman Avanasi Narasimhan, Mick A McGee, Quinn Dickinson, Alex La Reau, Dan Xie, Mingyuan Tian, Jennifer L Reed, Yaoping Zhang, Joshua J Coon, Chris Todd Hittinger, Audrey P Gasch, Robert Landick
The inability of native Saccharomyces cerevisiae to convert xylose from plant biomass into biofuels remains a major challenge for the production of renewable bioenergy. Despite extensive knowledge of the regulatory networks controlling carbon metabolism in yeast, little is known about how to reprogram S. cerevisiae to ferment xylose at rates comparable to glucose. Here we combined genome sequencing, proteomic profiling, and metabolomic analyses to identify and characterize the responsible mutations in a series of evolved strains capable of metabolizing xylose aerobically or anaerobically...
October 2016: PLoS Genetics
Alireza Karbalayghareh, Ulisses Braga-Neto, Jianping Hua, Edward R Dougherty
Gene-expression-based phenotype classification is used for disease diagnosis and prognosis relating to treatment strategies. The present paper considers classification based on sequential measurements of multiple genes using gene regulatory network (GRN) modeling. There are two networks, original and mutated, and observations consist of trajectories of network states. The problem is to classify an observation trajectory as coming from either the original or mutated network. GRNs are modeled via probabilistic Boolean networks, which incorporate stochasticity at both the gene and network levels...
October 11, 2016: IEEE/ACM Transactions on Computational Biology and Bioinformatics
Agata Stryjewska, Ruben Dries, Tim Pieters, Griet Verstappen, Andrea Conidi, Kathleen Coddens, Annick Francis, Lieve Umans, Wilfred F J van IJcken, Geert Berx, Leo A van Grunsven, Frank Grosveld, Steven Goossens, Jody J Haigh, Danny Huylebroeck
In human ESCs the transcription factor Zeb2 regulates neuroectoderm versus mesendoderm formation, but it is unclear how Zeb2 affects the global transcriptional regulatory network in these cell-fate decisions. We generated Zeb2 knockout (KO) mouse ESCs, subjected them as embryoid bodies (EBs) to neural and general differentiation and carried out temporal RNA-sequencing (RNA-seq) and reduced representation bisulfite sequencing (RRBS) analysis in neural differentiation. This shows that Zeb2 acts preferentially as a transcriptional repressor associated with developmental progression and that Zeb2 KO ESCs can exit from their naïve state...
October 14, 2016: Stem Cells
Vijay Gahlaut, Vandana Jaiswal, Anuj Kumar, Pushpendra Kumar Gupta
TFs involved in drought tolerance in plants may be utilized in future for developing drought tolerant cultivars of wheat and some other crops. Plants have developed a fairly complex stress response system to deal with drought and other abiotic stresses. These response systems often make use of transcription factors (TFs); a gene encoding a specific TF together with -its target genes constitute a regulon, and take part in signal transduction to activate/silence genes involved in response to drought. Since, five specific families of TFs (out of >80 known families of TFs) have gained widespread attention on account of their significant role in drought tolerance in plants, TFs and regulons belonging to these five multi-gene families (AP2/EREBP, bZIP, MYB/MYC, NAC and WRKY) have been described and their role in improving drought tolerance discussed in this brief review...
October 13, 2016: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
Hanna Taipaleenmäki, Nicholas H Farina, Andre J van Wijnen, Janet L Stein, Eric Hesse, Gary S Stein, Jane B Lian
Wnt signaling is implicated in bone formation and activated in breast cancer cells promoting primary and metastatic tumor growth. A compelling question is whether osteogenic miRNAs that increase Wnt activity for bone formation are aberrantly expressed in breast tumor cells to support metastatic bone disease. Here we report that miR-218-5p is highly expressed in bone metastases from breast cancer patients, but is not detected in normal mammary epithelial cells. Furthermore, inhibition of miR-218-5p impaired the growth of bone metastatic MDA-MB-231 cells in the bone microenvironment in vivo...
October 12, 2016: Oncotarget
Epameinondas Gousopoulos, Steven T Proulx, Samia B Bachmann, Jeannette Scholl, Dimitris Dionyssiou, Efterpi Demiri, Cornelia Halin, Lothar C Dieterich, Michael Detmar
Secondary lymphedema is a common postcancer treatment complication, but the underlying pathological processes are poorly understood and no curative treatment exists. To investigate lymphedema pathomechanisms, a top-down approach was applied, using genomic data and validating the role of a single target. RNA sequencing of lymphedematous mouse skin indicated upregulation of many T cell-related networks, and indeed depletion of CD4(+) cells attenuated lymphedema. The significant upregulation of Foxp3, a transcription factor specifically expressed by regulatory T cells (Tregs), along with other Treg-related genes, implied a potential role of Tregs in lymphedema...
October 6, 2016: JCI Insight
Sivan Subburaju, Andrew J Coleman, Miles G Cunningham, W Brad Ruzicka, Francine M Benes
GABAergic dysfunction in hippocampus, a key feature of schizophrenia (SZ), may contribute to cognitive impairment in this disorder. In stratum oriens (SO) of sector CA3/2 of the human hippocampus, a network of genes involved in the regulation of glutamic acid decarboxylase GAD67 has been identified. Several of the genes in this network including epigenetic factors histone deacetylase 1 (HDAC1) and death-associated protein 6 (DAXX), the GABAergic enzyme GAD65 as well as the kainate receptor (KAR) subunits GluR6 and 7 show significant changes in expression in this area in SZ...
October 12, 2016: Cerebral Cortex
Saiprasad Ramnarayanan, Chandrashekara Kyathanahalli, Judith Ingles, Miejung Park-York, Pancharatnam Jeyasuria, Jennifer C Condon
There is considerable evidence that implicates oxidative stress in the pathophysiology of human pregnancy complications. However the role and the mechanism of maintaining an anti-oxidant pro-survival uterine environment during normal pregnancy is largely unresolved. Herein we report the highly active uterine unfolded protein response plays a key role in promoting anti-oxidant activity in the uterine myocyte across gestation. The unfolded protein response senses the accumulation of misfolded proteins in the endoplasmic reticulum (ER) and activates a signaling network that consists of the transmembrane protein kinase eukaryotic translation initiation factor 2 alpha kinase 3/PKR-like-ER kinase (EIF2AK3), which acts to decrease protein translation levels allowing for a lowered need for protein folding during periods of ER stress...
October 12, 2016: Biology of Reproduction
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