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https://www.readbyqxmd.com/read/28343999/a-genome-wide-analysis-of-human-pluripotent-stem-cell-derived-endothelial-cells-in-2d-or-3d-culture
#1
Jue Zhang, Michael P Schwartz, Zhonggang Hou, Yongsheng Bai, Hamisha Ardalani, Scott Swanson, John Steill, Victor Ruotti, Angela Elwell, Bao Kim Nguyen, Jennifer Bolin, Ron Stewart, James A Thomson, William L Murphy
A defined protocol for efficiently deriving endothelial cells from human pluripotent stem cells was established and vascular morphogenesis was used as a model system to understand how synthetic hydrogels influence global biological function compared with common 2D and 3D culture platforms. RNA sequencing demonstrated that gene expression profiles were similar for endothelial cells and pericytes cocultured in polyethylene glycol (PEG) hydrogels or Matrigel, while monoculture comparisons identified distinct vascular signatures for each cell type...
March 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28334818/chromosomal-dynamics-predicted-by-an-elastic-network-model-explains-genome-wide-accessibility-and-long-range-couplings
#2
Natalie Sauerwald, She Zhang, Carl Kingsford, Ivet Bahar
Understanding the three-dimensional (3D) architecture of chromatin and its relation to gene expression and regulation is fundamental to understanding how the genome functions. Advances in Hi-C technology now permit us to study 3D genome organization, but we still lack an understanding of the structural dynamics of chromosomes. The dynamic couplings between regions separated by large genomic distances (>50 Mb) have yet to be characterized. We adapted a well-established protein-modeling framework, the Gaussian Network Model (GNM), to model chromatin dynamics using Hi-C data...
March 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28333290/evolution-of-the-genome-3d-organization-comparison-of-fused-and-segregated-globin-gene-clusters
#3
Anastasia P Kovina, Natalia V Petrova, Ekaterina S Gushchanskaya, Konstantin V Dolgushin, Evgeny S Gerasimov, Aleksandra A Galitsyna, Alexey A Penin, Ilya M Flyamer, Elena S Ioudinkova, Alexey A Gavrilov, Yegor S Vassetzky, Sergey V Ulianov, Olga V Iarovaia, Sergey V Razin
The genomes are folded in a complex three-dimensional (3D) structure. Some features of this organization are common for all eukaryotes, but little is known about its evolution. Here we have studied the 3D organization and regulation of zebrafish globin domain and compared its organization and regulation with those of other vertebrate species. In birds and mammals, the alpha- and beta-globin genes are segregated into separate clusters located on different chromosomes and organized into chromatin domains of different types, whereas in cold-blooded vertebrates, including Danio rerio, alpha- and beta-globin genes are organized into common clusters...
March 7, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/28331082/kaposi-s-sarcoma-associated-herpesvirus-hijacks-rna-polymerase-ii-to-create-a-viral-transcriptional-factory
#4
Christopher Phillip Chen, Yuanzhi Lyu, Frank Chuang, Kazushi Nakano, Chie Izumiya, Di Jin, Mel Campbell, Yoshihiro Izumiya
Locally concentrated nuclear factors ensure efficient binding to the DNA templates, facilitating RNA polymerase II recruitment and frequent reutilization of stable pre-initiation complexes. Here we have uncovered a mechanism for effective viral transcription by focal assembly of RNA polymerase II around KSHV genomes in the host cell nucleus. Using immunofluorescent labeling of latent nuclear antigen (LANA) protein, together with fluorescence in situ RNA hybridization (RNA-FISH) of the intron region of immediate-early transcripts, we visualized active transcription of viral genomes in naturally infected cells...
March 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28330874/high-resolution-3d-nmr-structure-of-the-kras-proto-oncogene-promoter-reveals-key-features-of-a-g-quadruplex-involved-in-transcriptional-regulation
#5
Abdelaziz Kerkour, Julien Marquevielle, Stefaniia Ivashchenko, Liliya A Yatsunyk, Jean-Louis Mergny, Gilmar F Salgado
Non-canonical base pairing within guanine-rich DNA and RNA sequences can produce G-quartets, whose stacking leads to the formation of a G-quadruplex (G4). G4s can coexist with canonical duplex DNA in the human genome and have been suggested to suppress gene transcription, and much attention has therefore focused on studying G4s in promotor regions of disease-related genes. For example, the human KRAS proto-oncogene contains a nuclease-hypersensitive element (1) located upstream of the major transcription start site...
March 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28322583/interplay-between-genetic-and-epigenetic-mechanisms-in-rheumatoid-arthritis
#6
Mojca Frank-Bertoncelj, Kerstin Klein, Steffen Gay
Genetic and environmental factors contribute to the risk for rheumatoid arthritis (RA), with epigenetics serving as a possible interface through which risk factors contribute to RA. High-throughput technologies for interrogating genome and epigenome, and the availability of genetic and epigenetic datasets across a diversity of cell types, enable the identification of candidate causal genetic variants for RA to study their function in core RA processes. To date, RA risk variants were studied in the immune cells but not joint resident cells, for example, synovial fibroblasts...
March 21, 2017: Epigenomics
https://www.readbyqxmd.com/read/28321632/metastatic-melanoma-moves-on-translational-science-in-the-era-of-personalized-medicine
#7
Mitchell P Levesque, Phil F Cheng, Marieke I G Raaijmakers, Annalisa Saltari, Reinhard Dummer
Progress in understanding and treating metastatic melanoma is the result of decades of basic and translational research as well as the development of better in vitro tools for modeling the disease. Here, we review the latest therapeutic options for metastatic melanoma and the known genetic and non-genetic mechanisms of resistance to these therapies, as well as the in vitro toolbox that has provided the greatest insights into melanoma progression. These include next-generation sequencing technologies and more complex 2D and 3D cell culture models to functionally test the data generated by genomics approaches...
March 20, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28320945/three-dimensional-culture-system-identifies-a-new-mode-of-cetuximab-resistance-and-disease-relevant-genes-in-colorectal-cancer
#8
Cunxi Li, Bhuminder Singh, Ramona Graves-Deal, Haiting Ma, Alina Starchenko, William H Fry, Yuanyuan Lu, Yang Wang, Galina Bogatcheva, Mohseen P Khan, Ginger L Milne, Shilin Zhao, Gregory Daniel Ayers, Nenggan Li, Huaying Hu, Mary Kay Washington, Timothy J Yeatman, Oliver G McDonald, Qi Liu, Robert J Coffey
We previously reported that single cells from a human colorectal cancer (CRC) cell line (HCA-7) formed either hollow single-layered polarized cysts or solid spiky masses when plated in 3D in type-I collagen. To begin in-depth analyses into whether clonal cysts and spiky masses possessed divergent properties, individual colonies of each morphology were isolated and expanded. The lines thus derived faithfully retained their parental cystic and spiky morphologies and were termed CC (cystic) and SC (spiky), respectively...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28298204/immunoglobulin-t-from-sea-bass-dicentrarchus-labrax-l-molecular-characterization-tissue-localization-and-expression-after-nodavirus-infection
#9
Francesco Buonocore, Valentina Stocchi, Noelia Nunez-Ortiz, Elisa Randelli, Marco Gerdol, Alberto Pallavicini, Angelo Facchiano, Chiara Bernini, Laura Guerra, Giuseppe Scapigliati, Simona Picchietti
BACKGROUND: Immunoglobulins (Igs) are fundamental components of the adaptive immune system of vertebrates, with the IgT/IgZ isotype specific of Teleosts. In this paper we describe the identification of an IgT heavy chain from the European sea bass (Dicentrarchus labrax L.), its molecular characterization and tissue mRNA localization by in situ hybridization. RESULTS: Sea bass IgT consists of 552 aa (Accession Number KM410929) and it contains a putative 19 amino acids long signal peptide and one potential N-glycosylation site...
March 15, 2017: BMC Molecular Biology
https://www.readbyqxmd.com/read/28289288/3d-structures-of-individual-mammalian-genomes-studied-by-single-cell-hi-c
#10
Tim J Stevens, David Lando, Srinjan Basu, Liam P Atkinson, Yang Cao, Steven F Lee, Martin Leeb, Kai J Wohlfahrt, Wayne Boucher, Aoife O'Shaughnessy-Kirwan, Julie Cramard, Andre J Faure, Meryem Ralser, Enrique Blanco, Lluis Morey, Miriam Sansó, Matthieu G S Palayret, Ben Lehner, Luciano Di Croce, Anton Wutz, Brian Hendrich, Dave Klenerman, Ernest D Laue
The folding of genomic DNA from the beads-on-a-string-like structure of nucleosomes into higher-order assemblies is crucially linked to nuclear processes. Here we calculate 3D structures of entire mammalian genomes using data from a new chromosome conformation capture procedure that allows us to first image and then process single cells. The technique enables genome folding to be examined at a scale of less than 100 kb, and chromosome structures to be validated. The structures of individual topological-associated domains and loops vary substantially from cell to cell...
March 13, 2017: Nature
https://www.readbyqxmd.com/read/28283009/-production-and-molecular-characterization-of-plasmodium-falciparum-recombinant-circumsporozoite-protein-with-37-nanp-and-4-nvdp-epitopes
#11
Yunus Uyar, Abdüssamed Akşit, Serkan Karaca, Şirin Sahra Ceylan, Merve Yürük
Malaria is caused by the protozoan parasite Plasmodium, the leading cause of death amongst the parasitic diseases. The disease is transmitted to human by the bites of female Anopheles mosquitoes. According to the World Health Organization (WHO) data, there were an estimated 214 million malaria cases and estimated 438.000 deaths occurred worldwide, in 2015. It is observed that 90% of all the deaths due to malaria occur in Africa. 78% of these cases were children who are under five years old. Intensive malaria interventions helped to reduce malaria incidence by 37% between 2000 and 2015...
January 2017: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28274266/rna-isolation-from-precision-cut-lung-slices-pcls-from-different-species
#12
Monika Niehof, Tobias Hildebrandt, Olga Danov, Kirsten Arndt, Jeannette Koschmann, Franziska Dahlmann, Tanja Hansen, Katherina Sewald
BACKGROUND: Functional 3D organ models such as precision-cut lung slices (PCLS) have recently captured the attention of biomedical research. To enable wider implementation in research and development, these new biologically relevant organ models are being constantly refined. A very important issue is to improve the preparation of high-quality RNA (ribonucleic acid) from PCLS for drug discovery and development of new therapies. Gene expression analysis at different levels is used as an important experimental readout...
March 9, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28270148/mdm4-actively-restrains-cytoplasmic-mtorc1-by-sensing-nutrient-availability
#13
Francesca Mancini, Emanuela Teveroni, Giusy Di Conza, Valentina Monteleone, Ivan Arisi, Marsha Pellegrino, Marianna Buttarelli, Luisa Pieroni, Mara D'Onofrio, Andrea Urbani, Alfredo Pontecorvi, Massimiliano Mazzone, Fabiola Moretti
BACKGROUND: Many tumor-related factors have shown the ability to affect metabolic pathways by paving the way for cancer-specific metabolic features. Here, we investigate the regulation of mTORC1 by MDM4, a p53-inhibitor with oncogenic or anti-survival activities depending on cell growth conditions. METHOD: MDM4-mTOR relationship was analysed through experiments of overexpression or silencing of endogenous proteins in cell culture and using purified proteins in vitro...
March 7, 2017: Molecular Cancer
https://www.readbyqxmd.com/read/28264068/quantitative-trait-locus-analysis-for-spikelet-shape-related-traits-in-wild-wheat-progenitor-aegilops-tauschii-implications-for-intraspecific-diversification-and-subspecies-differentiation
#14
Ryo Nishijima, Yuki Okamoto, Hitoshi Hatano, Shigeo Takumi
Wild diploid wheat Aegilops tauschii, the D-genome progenitor of common wheat, carries large genetic variation in spikelet and grain morphology. Two differentiated subspecies of Ae. tauschii, subspecies tauschii and strangulata, have been traditionally defined based on differences in spikelet morphology. Here, we first assessed six spikelet shape-related traits among 199 Ae. tauschii accessions, and found that the accessions belonging to TauL1major lineage produced significantly longer spikes, higher spikelet density, and shorter, narrower spikelets than another major lineage, TauL2, in which the strangulata accessions are included...
2017: PloS One
https://www.readbyqxmd.com/read/28263319/asymmetric-subgenome-selection-and-cis-regulatory-divergence-during-cotton-domestication
#15
Maojun Wang, Lili Tu, Min Lin, Zhongxu Lin, Pengcheng Wang, Qingyong Yang, Zhengxiu Ye, Chao Shen, Jianying Li, Lin Zhang, Xiaolin Zhou, Xinhui Nie, Zhonghua Li, Kai Guo, Yizan Ma, Cong Huang, Shuangxia Jin, Longfu Zhu, Xiyan Yang, Ling Min, Daojun Yuan, Qinghua Zhang, Keith Lindsey, Xianlong Zhang
Comparative population genomics offers an excellent opportunity for unraveling the genetic history of crop domestication. Upland cotton (Gossypium hirsutum) has long been an important economic crop, but a genome-wide and evolutionary understanding of the effects of human selection is lacking. Here, we describe a variation map for 352 wild and domesticated cotton accessions. We scanned 93 domestication sweeps occupying 74 Mb of the A subgenome and 104 Mb of the D subgenome, and identified 19 candidate loci for fiber-quality-related traits through a genome-wide association study...
March 6, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28261265/new-insights-into-transcriptional-and-leukemogenic-mechanisms-of-aml1-eto-and-e2a-fusion-proteins
#16
Jian Li, Chun Guo, Nickolas Steinauer, Jinsong Zhang
BACKGROUND: Nearly 15% of acute myeloid leukemia (AML) cases are caused by aberrant expression of AML1-ETO, a fusion protein generated by the t(8;21) chromosomal translocation. Since its discovery, AML1-ETO has served as a prototype to understand how leukemia fusion proteins deregulate transcription to promote leukemogenesis. Another leukemia fusion protein, E2A-Pbx1, generated by the t(1;19) translocation, is involved in acute lymphoblastic leukemias (ALLs). While AML1-ETO and E2A-Pbx1 are structurally unrelated fusion proteins, we have recently shown that a common axis, the ETO/E-protein interaction, is involved in the regulation of both fusion proteins, underscoring the importance of studying protein-protein interactions in elucidating the mechanisms of leukemia fusion proteins...
August 2016: Frontiers in Biology
https://www.readbyqxmd.com/read/28251877/genomic-landscape-of-cpg-rich-elements-in-human
#17
Vladimir N Babenko, Irina V Chadaeva, Yuriy L Orlov
BACKGROUND: The studies on CpG islands (CGI) and Alu elements functions, evolution, and distribution in the genome started since the discovery in nineteen eighties (1981, 1986, correspondingly). Their highly skewed genome wide distribution implies the non-random retrotransposition pattern. Besides CGIs in gene promoters, CGIs clusters were observed in the homeobox gene regions and in the macrosatellites, but the whole picture of their distribution specifics was not grasped. Attempts to identify any causative features upon their (genome wide) distribution, such as the DNA context mediated preferred insertion sites of Alu repeats, have been made to ascribe their clusters location...
February 7, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/28251841/topologically-associated-domains-a-successful-scaffold-for-the-evolution-of-gene-regulation-in-animals
#18
REVIEW
Rafael D Acemel, Ignacio Maeso, José Luis Gómez-Skarmeta
The evolution of gene regulation is considered one of the main drivers causing the astonishing morphological diversity in the animal kingdom. Gene regulation in animals heavily depends upon cis-regulatory elements, discrete pieces of DNA that interact with target promoters to regulate gene expression. In the last years, Chromosome Conformation Capture experiments (4C-seq, 5C, and HiC) in several organisms have shown that the genomes of many bilaterian animals are organized in the 3D chromatin space in compartments called topologically associated domains (TADs)...
March 2, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28244183/nonketotic-hyperglycinemia-functional-assessment-of-missense-variants-in-gldc-to-understand-phenotypes-of-the-disease
#19
Irene Bravo-Alonso, Rosa Navarrete, Laura Arribas-Carreira, Almudena Perona, David Abia, María Luz Couce, Angels García-Cazorla, Ana Morais, Rosario Domingo, María Antonia Ramos, Michael A Swanson, Johan L K Van Hove, Magdalena Ugarte, Belén Pérez, Celia Pérez-Cerdá, Pilar Rodríguez-Pombo
The rapid analysis of genomic data is providing effective mutational confirmation in patients with clinical and biochemical hallmarks of a specific disease. This is the case for Nonketotic Hyperglycinemia (NKH), a Mendelian disorder causing seizures in neonates and early-infants, primarily due to mutations in the GLDC gene. However, understanding the impact of missense-variants identified in this gene is a major challenge for the application of genomics into clinical practice. Herein, a comprehensive functional and structural analysis of 19 GLDC missense-variants identified in a cohort of 26 NKH patients was performed...
February 28, 2017: Human Mutation
https://www.readbyqxmd.com/read/28240214/genomic-alterations-of-non-coding-regions-underlie-human-cancer-lessons-from-t-all
#20
REVIEW
Adrian Rivera-Reyes, Katharina E Hayer, Craig H Bassing
It has been appreciated for decades that somatic genomic alterations that change coding sequences of proto-oncogenes, translocate enhancers/promoters near proto-oncogenes, or create fusion oncogenes can drive cancer by inducing oncogenic activities. An explosion of genome-wide technologies over the past decade has fueled discoveries of the roles of three-dimensional chromosome structure and powerful cis-acting elements (super-enhancers) in regulating gene transcription. In recent years, studies of human T cell acute lymphoblastic leukemia (T-ALL) using genome-wide technologies have provided paradigms for how non-coding genomic region alterations can disrupt 3D chromosome architecture or establish super-enhancers to activate oncogenic transcription of proto-oncogenes...
December 2016: Trends in Molecular Medicine
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