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Tissue specific gene network

Hyejung Won, Luis de la Torre-Ubieta, Jason L Stein, Neelroop N Parikshak, Jerry Huang, Carli K Opland, Michael J Gandal, Gavin J Sutton, Farhad Hormozdiari, Daning Lu, Changhoon Lee, Eleazar Eskin, Irina Voineagu, Jason Ernst, Daniel H Geschwind
Three-dimensional physical interactions within chromosomes dynamically regulate gene expression in a tissue-specific manner. However, the 3D organization of chromosomes during human brain development and its role in regulating gene networks dysregulated in neurodevelopmental disorders, such as autism or schizophrenia, are unknown. Here we generate high-resolution 3D maps of chromatin contacts during human corticogenesis, permitting large-scale annotation of previously uncharacterized regulatory relationships relevant to the evolution of human cognition and disease...
October 19, 2016: Nature
Qiangfeng Wang, Huanxia Yang, Lingjiao Wu, Jian Yao, Xiaohua Meng, Han Jiang, Cheng Xiao, Fusheng Wu
BACKGROUND: In recent years, long non-coding RNAs (lncRNAs) have been shown to play a critical regulatory role in cancer biology. However, the contribution of lncRNAs to papillary thyroid cancer (PTC) remains largely unknown. METHODS: RNA sequencing and quantitative reverse transcription PCR (qRT-PCR) were used to detect and verify, respectively, changes to the transcriptomic profile in 12 PTC tissues compared to paired normal adjacent tissues. The statistical correlation between differentially expressed lncRNAs and clinicopathological characteristics was analysed, and potential lncRNA functions were predicted by examining annotations for the co-expressed mRNAs...
October 19, 2016: Thyroid: Official Journal of the American Thyroid Association
Christophe Ampe, Marleen Van Troys
Actin is the central building block of the actin cytoskeleton, a highly regulated filamentous network enabling dynamic processes of cells and simultaneously providing structure. Mammals have six actin isoforms that are very conserved and thus share common functions. Tissue-specific expression in part underlies their differential roles, but actin isoforms also coexist in various cell types and tissues, suggesting specific functions and preferential interaction partners. Gene deletion models, antibody-based staining patterns, gene silencing effects, and the occurrence of isoform-specific mutations in certain diseases have provided clues for specificity on the subcellular level and its consequences on the organism level...
October 19, 2016: Handbook of Experimental Pharmacology
Hjalte C R Sass, Rehannah Borup, Mikkel Alanin, Finn Cilius Nielsen, Per Cayé-Thomasen
The objective of this study was to determine global gene expression in relation to Vestibular schwannomas (VS) growth rate and to identify signal transduction pathways and functional molecular networks associated with growth. Repeated magnetic resonance imaging (MRI) prior to surgery determined tumor growth rate. Following tissue sampling during surgery, mRNA was extracted from 16 sporadic VS. Double stranded cDNA was synthesized from the mRNA and used as template for in vitro transcription reaction to synthesize biotin-labeled antisense cRNA, which was hybridized to Affymetrix HG-U133A arrays and analyzed by dChip software...
October 17, 2016: Journal of Neuro-oncology
Maksim Kitsak, Amitabh Sharma, Jörg Menche, Emre Guney, Susan Dina Ghiassian, Joseph Loscalzo, Albert-László Barabási
Genes carrying mutations associated with genetic diseases are present in all human cells; yet, clinical manifestations of genetic diseases are usually highly tissue-specific. Although some disease genes are expressed only in selected tissues, the expression patterns of disease genes alone cannot explain the observed tissue specificity of human diseases. Here we hypothesize that for a disease to manifest itself in a particular tissue, a whole functional subnetwork of genes (disease module) needs to be expressed in that tissue...
October 17, 2016: Scientific Reports
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
Anne-Laure Chateigner-Boutin, José J Ordaz-Ortiz, Camille Alvarado, Brigitte Bouchet, Sylvie Durand, Yves Verhertbruggen, Yves Barrière, Luc Saulnier
Cell walls are comprised of networks of entangled polymers that differ considerably between species, tissues and developmental stages. The cell walls of grasses, a family that encompasses major crops, contain specific polysaccharide structures such as xylans substituted with feruloylated arabinose residues. Ferulic acid is involved in the grass cell wall assembly by mediating linkages between xylan chains and between xylans and lignins. Ferulic acid contributes to the physical properties of cell walls, it is a hindrance to cell wall degradability (thus biomass conversion and silage digestibility) and may contribute to pest resistance...
2016: Frontiers in Plant Science
Josh Clevenger, Ye Chu, Brian Scheffler, Peggy Ozias-Akins
The advent of the genome sequences of Arachis duranensis and Arachis ipaensis has ushered in a new era for peanut genomics. With the goal of producing a gene atlas for cultivated peanut (Arachis hypogaea), 22 different tissue types and ontogenies that represent the full development of peanut were sequenced, including a complete reproductive series from flower to peg elongation and peg tip immersion in the soil to fully mature seed. Using a genome-guided assembly pipeline, a homeolog-specific transcriptome assembly for Arachis hypogaea was assembled and its accuracy was validated...
2016: Frontiers in Plant Science
Jennifer Jurkin, Corinna Krump, René Köffel, Christina Fieber, Christopher Schuster, Patrick M Brunner, Izabela Borek, Gregor Eisenwort, Clarice Lim, Jörg Mages, Roland Lang, Wolfgang Bauer, Diana Mechtcheriakova, Anastasia Meshcheryakova, Adelheid Elbe-Bürger, Georg Stingl, Herbert Strobl
BACKGROUND: Langerhans cell (LC) networks play key roles in immunity and tolerance at body surfaces. LCs are established prenatally and can be replenished from blood monocytes. Unlike skin-resident dermal/interstitial-type DCs (d/intDCs) and inflammatory dendritic epidermal cells (IDECs) appearing in dermatitis/eczema lesions, LCs lack key monocyte-affiliated markers. Inversely, LCs express various epithelial genes critical for their long-term peripheral tissue residency. OBJECTIVE: DCs are functionally involved in inflammatory diseases; however, mechanisms remained poorly understood...
October 11, 2016: Journal of Allergy and Clinical Immunology
Kaye Showler, Mayumi Nishimura, Kazuhiro Daino, Tatsuhiko Imaoka, Yukiko Nishimura, Takamitsu Morioka, Benjamin J Blyth, Toshiaki Kokubo, Masaru Takabatake, Maki Fukuda, Hitomi Moriyama, Shizuko Kakinuma, Masahiro Fukushi, Yoshiya Shimada
The PI3K/AKT pathway is one of the most important signaling networks in human breast cancer, and since it was potentially implicated in our preliminary investigations of radiation-induced rat mammary carcinomas, our aim here was to verify its role. We included mammary carcinomas induced by the chemical carcinogen 1-methyl-1-nitrosourea to determine whether any changes were radiation-specific. Most carcinomas from both groups showed activation of the PI3K/AKT pathway, but phosphorylation of AKT1 was often heterogeneous and only present in a minority of carcinoma cells...
October 13, 2016: Journal of Radiation Research
Helen Ross-Adams, Stephen Ball, Kate Lawrenson, Silvia Halim, Roslin Russell, Claire Wells, Siri H Strand, Torben F Ørntoft, Melissa Larson, Sebastian Armasu, Charles E Massie, Mohammad Asim, Martin M Mortensen, Michael Borre, Kathryn Woodfine, Anne Y Warren, Alastair D Lamb, Jonathan Kay, Hayley Whitaker, Antonio Ramos-Montoya, Adele Murrell, Karina D Sørensen, Brooke L Fridley, Ellen L Goode, Simon A Gayther, John Masters, David E Neal, Ian G Mills
Two independent regions within HNF1B are consistently identified in prostate and ovarian cancer genome-wide association studies (GWAS); their functional roles are unclear. We link prostate cancer (PC) risk SNPs rs11649743 and rs3760511 with elevated HNF1B gene expression and allele-specific epigenetic silencing, and outline a mechanism by which common risk variants could effect functional changes that increase disease risk: functional assays suggest that HNF1B is a pro-differentiation factor that suppresses epithelial-to-mesenchymal transition (EMT) in unmethylated, healthy tissues...
October 9, 2016: Oncotarget
Amer Sehic, Amela Tulek, Cuong Khuu, Minou Nirvani, Lars Peter Sand, Tor Paaske Utheim
MicroRNAs (miRNAs) are a class of small, non-coding RNAs that provide an efficient pathway for regulation of gene expression at a post-transcriptional level. Tooth development is regulated by a complex network of cell-cell signaling during all steps of organogenesis. Most of the congenital dental defects in humans are caused by mutations in genes involved in developmental regulatory networks. Whereas the developmental morphological stages of the tooth development already are thoroughly documented, the implicated genetic network is still under investigation...
October 7, 2016: Gene
Joelle M Fenger, Ryan D Roberts, O Hans Iwenofu, Misty D Bear, Xiaoli Zhang, Jason I Couto, Jaime F Modiano, William C Kisseberth, Cheryl A London
BACKGROUND: MicroRNAs (miRNAs) regulate the expression of networks of genes and their dysregulation is well documented in human malignancies; however, limited information exists regarding the impact of miRNAs on the development and progression of osteosarcoma (OS). Canine OS exhibits clinical and molecular features that closely resemble the corresponding human disease and it is considered a well-established spontaneous animal model to study OS biology. The purpose of this study was to investigate miRNA dysregulation in canine OS...
October 10, 2016: BMC Cancer
Michael Seifert, Betty Friedrich, Andreas Beyer
It has proven exceedingly difficult to ascertain rare copy number alterations (CNAs) that may have strong effects in individual tumors. We show that a regulatory network inferred from gene expression and gene copy number data of 768 human cancer cell lines can be used to quantify the impact of patient-specific CNAs on survival signature genes. A focused analysis of tumors from six tissues reveals that rare patient-specific gene CNAs often have stronger effects on signature genes than frequent gene CNAs. Further comparison to a related network-based approach shows that the integration of indirectly acting gene CNAs significantly improves the survival analysis...
October 3, 2016: Genome Biology
Marc-Emmanuel Dumas, Céline Domange, Sophie Calderari, Andrea Rodríguez Martínez, Rafael Ayala, Steven P Wilder, Nicolas Suárez-Zamorano, Stephan C Collins, Robert H Wallis, Quan Gu, Yulan Wang, Christophe Hue, Georg W Otto, Karène Argoud, Vincent Navratil, Steve C Mitchell, John C Lindon, Elaine Holmes, Jean-Baptiste Cazier, Jeremy K Nicholson, Dominique Gauguier
BACKGROUND: The genetic regulation of metabolic phenotypes (i.e., metabotypes) in type 2 diabetes mellitus occurs through complex organ-specific cellular mechanisms and networks contributing to impaired insulin secretion and insulin resistance. Genome-wide gene expression profiling systems can dissect the genetic contributions to metabolome and transcriptome regulations. The integrative analysis of multiple gene expression traits and metabolic phenotypes (i.e., metabotypes) together with their underlying genetic regulation remains a challenge...
September 30, 2016: Genome Medicine
Heng Xia, Libin Zhang, Gang Wu, Chunhua Fu, Yan Long, Jun Xiang, Jianping Gan, Yanhong Zhou, Longjiang Yu, Maoteng Li
MiRNAs function in post-transcriptional regulation of gene expression and play very important roles in plant development. Lonicera japonica is one of the important medicinal plants in China. However, few studies on the discovery of conserved and novel miRNAs from L. japonica were reported. In this study, we employed deep sequencing technology to identify miRNAs in leaf and flower tissues of L. japonica. A total of 22.97 million clean reads from flower and leaf tissues were obtained, which generated 146 conserved miRNAs distributed in 20 families and 110 novel miRNAs...
2016: PloS One
Liyun Miao, Libin Zhang, Nadia Raboanatahiry, Guangyuan Lu, Xuekun Zhang, Jun Xiang, Jianping Gan, Chunhua Fu, Maoteng Li
Brassica napus is one of the most important oilseed crops in the world. However, there is currently no enough stem transcriptome information and comparative transcriptome analysis of different tissues, which impedes further functional genomics research on B. napus. In this study, the stem transcriptome of B. napus was characterized by RNA-seq technology. Approximately 13.4 Gb high-quality clean reads with an average length of 100 bp were generated and used for comparative transcriptome analysis with the existing transcriptome sequencing data of roots, leaves, flower buds, and immature embryos of B...
2016: Frontiers in Plant Science
Z Z Liu, S T Cui, B Tang, Z Z Wang, Z X Luan
The aim of this study was to screen for key biomarkers of osteosarcoma (OS) by tracking altered modules. Protein-protein interaction (PPI) networks of OS and normal groups were constructed and re-weighted using the Pearson correlation coefficient (PCC), respectively. The condition-specific modules were explored from OS and normal PPI networks using a clique-merging algorithm. Altered modules were identified by a maximum weight bipartite-matching method. The important biological pathways in OS were identified by a pathway-enrichment analysis using genes from disrupted modules...
August 26, 2016: Genetics and Molecular Research: GMR
Simon C Johnson, Brenda Gonzalez, Quanwei Zhang, Brandon Milholland, Zhengdong Zhang, Yousin Suh
While mitochondria have been linked to many human diseases through genetic association and functional studies, the precise role of mitochondria in specific pathologies, such as cardiovascular, neurodegenerative, and metabolic diseases, is often unclear. Here, we take advantage of the catalog of human genome-wide associations, whole-genome tissue expression and expression quantitative trait loci datasets, and annotated mitochondrial proteome databases to examine the role of common genetic variation in mitonuclear genes in human disease...
October 4, 2016: Human Genetics
Ana L Salgado, Tomasz Suchan, Loïc Pellissier, Sergio Rasmann, Anne-Lyse Ducrest, Nadir Alvarez
Elevation gradients impose large differences in abiotic and biotic conditions over short distances, in turn, likely driving differences in gene expression more than would genetic variation per se, as natural selection and drift are less likely to fix alleles at such a narrow spatial scale. As elevation increases, the pressure exerted on plants by herbivores and on arthropod herbivores by predators decreases, and organisms spanning the elevation gradient are thus expected to show lower levels of defence at high elevation...
September 2016: Royal Society Open Science
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