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John rinn

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https://www.readbyqxmd.com/read/29039474/evaluation-of-a-radiocobalt-labelled-affibody-molecule-for-imaging-of-human-epidermal-growth-factor-receptor-3-expression
#1
Maria Rosestedt, Ken G Andersson, Bogdan Mitran, Sara S Rinne, Vladimir Tolmachev, John Löfblom, Anna Orlova, Stefan Ståhl
The human epidermal growth factor receptor 3 (HER3) is involved in the development of cancer resistance towards tyrosine kinase-targeted therapies. Several HER3‑targeting therapeutics are currently under clinical evaluation. Non-invasive imaging of HER3 expression could improve patient management. Affibody molecules are small engineered scaffold proteins demonstrating superior properties as targeting probes for molecular imaging compared with monoclonal antibodies. Feasibility of in vivo HER3 imaging using affibody molecules has been previously demonstrated...
October 11, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28973438/p53-regulates-enhancer-accessibility-and-activity-in-response-to-dna-damage
#2
Scott T Younger, John L Rinn
The tumor suppressor p53 is a well-characterized transcription factor that can bind gene promoters and regulate target gene transcription in response to DNA damage. Recent studies, however, have revealed that p53 binding events occur predominantly within regulatory enhancer elements. The effect of p53 binding on enhancer function has not been systematically evaluated. Here, we perform a genome-scale analysis of enhancer activity from p53-bound sequences using a series of massively parallel reporter assays (MPRAs) coupled with the assay for transposase-accessible chromatin (ATAC-Seq)...
September 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28930659/group-1-innate-lymphoid-cell-lineage-identity-is-determined-by-a-cis-regulatory-element-marked-by-a-long-non-coding-rna
#3
Walter K Mowel, Sam J McCright, Jonathan J Kotzin, Magalie A Collet, Asli Uyar, Xin Chen, Alexandra DeLaney, Sean P Spencer, Anthony T Virtue, EnJun Yang, Alejandro Villarino, Makoto Kurachi, Margaret C Dunagin, Gretchen Harms Pritchard, Judith Stein, Cynthia Hughes, Diogo Fonseca-Pereira, Henrique Veiga-Fernandes, Arjun Raj, Taku Kambayashi, Igor E Brodsky, John J O'Shea, E John Wherry, Loyal A Goff, John L Rinn, Adam Williams, Richard A Flavell, Jorge Henao-Mejia
Commitment to the innate lymphoid cell (ILC) lineage is determined by Id2, a transcriptional regulator that antagonizes T and B cell-specific gene expression programs. Yet how Id2 expression is regulated in each ILC subset remains poorly understood. We identified a cis-regulatory element demarcated by a long non-coding RNA (lncRNA) that controls the function and lineage identity of group 1 ILCs, while being dispensable for early ILC development and homeostasis of ILC2s and ILC3s. The locus encoding this lncRNA, which we termed Rroid, directly interacted with the promoter of its neighboring gene, Id2, in group 1 ILCs...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28875933/lncrna-requirements-for-mouse-acute-myeloid-leukemia-and-normal-differentiation
#4
M Joaquina Delás, Leah R Sabin, Egor Dolzhenko, Simon Rv Knott, Ester Munera Maravilla, Benjamin T Jackson, Sophia A Wild, Tatjana Kovacevic, Eva Maria Stork, Meng Zhou, Nicolas Erard, Emily Lee, David R Kelley, Mareike Roth, Ine S Am Barbosa, Johannes Zuber, John L Rinn, Andrew D Smith, Gregory J Hannon
A substantial fraction of the genome is transcribed in a cell-type-specific manner, producing long non-coding RNAs (lncRNAs), rather than protein-coding transcripts. Here, we systematically characterize transcriptional dynamics during hematopoiesis and in hematological malignancies. Our analysis of annotated and de novo assembled lncRNAs showed many are regulated during differentiation and mis-regulated in disease. We assessed lncRNA function via an in vivo RNAi screen in a model of acute myeloid leukemia. This identified several lncRNAs essential for leukemia maintenance, and found that a number act by promoting leukemia stem cell signatures...
September 6, 2017: ELife
https://www.readbyqxmd.com/read/28698299/neat1-is-a-p53-inducible-lincrna-essential-for-transformation-suppression
#5
Stephano S Mello, Carolyn Sinow, Nitin Raj, Pawel K Mazur, Kathryn Bieging-Rolett, Daniela Kenzelmann Broz, Jamie F Conklin Imam, Hannes Vogel, Laura D Wood, Julien Sage, Tetsuro Hirose, Shinichi Nakagawa, John Rinn, Laura D Attardi
The p53 gene is mutated in over half of all cancers, reflecting its critical role as a tumor suppressor. Although p53 is a transcriptional activator that induces myriad target genes, those p53-inducible genes most critical for tumor suppression remain elusive. Here, we leveraged p53 ChIP-seq (chromatin immunoprecipitation [ChIP] combined with high-throughput sequencing) and RNA-seq (RNA sequencing) data sets to identify new p53 target genes, focusing on the noncoding genome. We identify Neat1, a noncoding RNA (ncRNA) constituent of paraspeckles, as a p53 target gene broadly induced by mouse and human p53 in different cell types and by diverse stress signals...
June 1, 2017: Genes & Development
https://www.readbyqxmd.com/read/28561737/synergistic-interactions-with-pi3k-inhibition-that-induce-apoptosis
#6
Yaara Zwang, Oliver Jonas, Casandra Chen, Mikael L Rinne, John G Doench, Federica Piccioni, Li Tan, Hai-Tsang Huang, Jinhua Wang, Young Jin Ham, Joyce O'Connell, Patrick Bhola, Mihir Doshi, Matthew Whitman, Michael Cima, Anthony Letai, David E Root, Robert S Langer, Nathanael Gray, William C Hahn
Activating mutations involving the PI3K pathway occur frequently in human cancers. However, PI3K inhibitors primarily induce cell cycle arrest, leaving a significant reservoir of tumor cells that may acquire or exhibit resistance. We searched for genes that are required for the survival of PI3K mutant cancer cells in the presence of PI3K inhibition by conducting a genome scale shRNA-based apoptosis screen in a PIK3CA mutant human breast cancer cell. We identified 5 genes (PIM2, ZAK, TACC1, ZFR, ZNF565) whose suppression induced cell death upon PI3K inhibition...
May 31, 2017: ELife
https://www.readbyqxmd.com/read/28315828/weber-s-and-rinne-s-tests-bad-vibrations
#7
Iain John McGurgan, David Joseph Nicholl
No abstract text is available yet for this article.
August 2017: Practical Neurology
https://www.readbyqxmd.com/read/27927715/chromatin-environment-transcriptional-regulation-and-splicing-distinguish-lincrnas-and-mrnas
#8
Marta Melé, Kaia Mattioli, William Mallard, David M Shechner, Chiara Gerhardinger, John L Rinn
While long intergenic noncoding RNAs (lincRNAs) and mRNAs share similar biogenesis pathways, these transcript classes differ in many regards. LincRNAs are less evolutionarily conserved, less abundant, and more tissue-specific, suggesting that their pre- and post-transcriptional regulation is different from that of mRNAs. Here, we perform an in-depth characterization of the features that contribute to lincRNA regulation in multiple human cell lines. We find that lincRNA promoters are depleted of transcription factor (TF) binding sites, yet enriched for some specific factors such as GATA and FOS relative to mRNA promoters...
January 2017: Genome Research
https://www.readbyqxmd.com/read/27626181/linc00520-is-induced-by-src-stat3-and-pi3k-and-plays-a-functional-role-in-breast-cancer
#9
Whitney S Henry, David G Hendrickson, Francisco Beca, Benjamin Glass, Marianne Lindahl-Allen, Lizhi He, Zhe Ji, Kevin Struhl, Andrew H Beck, John L Rinn, Alex Toker
Long non-coding RNAs (lncRNAs) have been implicated in normal cellular homeostasis as well as pathophysiological conditions, including cancer. Here we performed global gene expression profiling of mammary epithelial cells transformed by oncogenic v-Src, and identified a large subset of uncharacterized lncRNAs potentially involved in breast cancer development. Specifically, our analysis revealed a novel lncRNA, LINC00520 that is upregulated upon ectopic expression of oncogenic v-Src, in a manner that is dependent on the transcription factor STAT3...
December 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27595844/in-vivo-ebola-virus-infection-leads-to-a-strong-innate-response-in-circulating-immune-cells
#10
Ignacio S Caballero, Anna N Honko, Stephen K Gire, Sarah M Winnicki, Marta Melé, Chiara Gerhardinger, Aaron E Lin, John L Rinn, Pardis C Sabeti, Lisa E Hensley, John H Connor
BACKGROUND: Ebola virus is the causative agent of a severe syndrome in humans with a fatality rate that can approach 90 %. During infection, the host immune response is thought to become dysregulated, but the mechanisms through which this happens are not entirely understood. In this study, we analyze RNA sequencing data to determine the host response to Ebola virus infection in circulating immune cells. RESULTS: Approximately half of the 100 genes with the strongest early increases in expression were interferon-stimulated genes, such as ISG15, OAS1, IFIT2, HERC5, MX1 and DHX58...
September 5, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27525555/the-long-non-coding-rna-morrbid-regulates-bim-and-short-lived-myeloid-cell-lifespan
#11
Jonathan J Kotzin, Sean P Spencer, Sam J McCright, Dinesh B Uthaya Kumar, Magalie A Collet, Walter K Mowel, Ellen N Elliott, Asli Uyar, Michelle A Makiya, Margaret C Dunagin, Christian C D Harman, Anthony T Virtue, Stella Zhu, Will Bailis, Judith Stein, Cynthia Hughes, Arjun Raj, E John Wherry, Loyal A Goff, Amy D Klion, John L Rinn, Adam Williams, Richard A Flavell, Jorge Henao-Mejia
Neutrophils, eosinophils and 'classical' monocytes collectively account for about 70% of human blood leukocytes and are among the shortest-lived cells in the body. Precise regulation of the lifespan of these myeloid cells is critical to maintain protective immune responses and minimize the deleterious consequences of prolonged inflammation. However, how the lifespan of these cells is strictly controlled remains largely unknown. Here we identify a long non-coding RNA that we termed Morrbid, which tightly controls the survival of neutrophils, eosinophils and classical monocytes in response to pro-survival cytokines in mice...
September 8, 2016: Nature
https://www.readbyqxmd.com/read/27524623/in%C3%A2-vivo-characterization-of-linc-p21-reveals-functional-cis-regulatory-dna-elements
#12
Abigail F Groff, Diana B Sanchez-Gomez, Marcela M L Soruco, Chiara Gerhardinger, A Rasim Barutcu, Eric Li, Lara Elcavage, Olivia Plana, Lluvia V Sanchez, James C Lee, Martin Sauvageau, John L Rinn
The Linc-p21 locus, encoding a long non-coding RNA, plays an important role in p53 signaling, cell-cycle regulation, and tumor suppression. However, despite extensive study, confusion exists regarding its mechanism of action: is activity driven by the transcript acting in trans, in cis, or by an underlying functional enhancer? Here, using a knockout mouse model and a massively parallel enhancer assay, we delineate the functional elements at this locus. We observe that, even in tissues with no detectable Linc-p21 transcript, deletion of the locus significantly affects local gene expression, including of the cell-cycle regulator Cdkn1a...
August 23, 2016: Cell Reports
https://www.readbyqxmd.com/read/27259198/-cat-s-cradling-the-3d-genome-by-the-act-of-lncrna-transcription
#13
REVIEW
Marta Melé, John L Rinn
There is growing evidence that transcription and nuclear organization are tightly linked. Yet, whether transcription of thousands of long noncoding RNAs (lncRNAs) could play a role in this packaging process remains elusive. Although some lncRNAs have been found to have clear roles in nuclear architecture (e.g., FIRRE, NEAT1, XIST, and others), the vast majority remain poorly understood. In this Perspective, we highlight how the act of transcription can affect nuclear architecture. We synthesize several recent findings into a proposed model where the transcription of lncRNAs can serve as guide-posts for shaping genome organization...
June 2, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27197224/basset-learning-the-regulatory-code-of-the-accessible-genome-with-deep-convolutional-neural-networks
#14
David R Kelley, Jasper Snoek, John L Rinn
The complex language of eukaryotic gene expression remains incompletely understood. Despite the importance suggested by many noncoding variants statistically associated with human disease, nearly all such variants have unknown mechanisms. Here, we address this challenge using an approach based on a recent machine learning advance-deep convolutional neural networks (CNNs). We introduce the open source package Basset to apply CNNs to learn the functional activity of DNA sequences from genomics data. We trained Basset on a compendium of accessible genomic sites mapped in 164 cell types by DNase-seq, and demonstrate greater predictive accuracy than previous methods...
July 2016: Genome Research
https://www.readbyqxmd.com/read/27078102/a-distant-trophoblast-specific-enhancer-controls-hla-g-expression-at-the-maternal-fetal-interface
#15
Leonardo M R Ferreira, Torsten B Meissner, Tarjei S Mikkelsen, William Mallard, Charles W O'Donnell, Tamara Tilburgs, Hannah A B Gomes, Raymond Camahort, Richard I Sherwood, David K Gifford, John L Rinn, Chad A Cowan, Jack L Strominger
HLA-G, a nonclassical HLA molecule uniquely expressed in the placenta, is a central component of fetus-induced immune tolerance during pregnancy. The tissue-specific expression of HLA-G, however, remains poorly understood. Here, systematic interrogation of the HLA-G locus using massively parallel reporter assay (MPRA) uncovered a previously unidentified cis-regulatory element 12 kb upstream of HLA-G with enhancer activity, Enhancer L Strikingly, clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9-mediated deletion of this enhancer resulted in ablation of HLA-G expression in JEG3 cells and in primary human trophoblasts isolated from placenta...
May 10, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27058446/biallelic-mutations-in-pde10a-lead-to-loss-of-striatal-pde10a-and-a-hyperkinetic-movement-disorder-with-onset-in-infancy
#16
Christine P Diggle, Stacey J Sukoff Rizzo, Michael Popiolek, Reetta Hinttala, Jan-Philip Schülke, Manju A Kurian, Ian M Carr, Alexander F Markham, David T Bonthron, Christopher Watson, Saghira Malik Sharif, Veronica Reinhart, Larry C James, Michelle A Vanase-Frawley, Erik Charych, Melanie Allen, John Harms, Christopher J Schmidt, Joanne Ng, Karen Pysden, Christine Strick, Päivi Vieira, Katariina Mankinen, Hannaleena Kokkonen, Matti Kallioinen, Raija Sormunen, Juha O Rinne, Jarkko Johansson, Kati Alakurtti, Laura Huilaja, Tiina Hurskainen, Kaisa Tasanen, Eija Anttila, Tiago Reis Marques, Oliver Howes, Marius Politis, Somayyeh Fahiminiya, Khanh Q Nguyen, Jacek Majewski, Johanna Uusimaa, Eamonn Sheridan, Nicholas J Brandon
Deficits in the basal ganglia pathways modulating cortical motor activity underlie both Parkinson disease (PD) and Huntington disease (HD). Phosphodiesterase 10A (PDE10A) is enriched in the striatum, and animal data suggest that it is a key regulator of this circuitry. Here, we report on germline PDE10A mutations in eight individuals from two families affected by a hyperkinetic movement disorder due to homozygous mutations c.320A>G (p.Tyr107Cys) and c.346G>C (p.Ala116Pro). Both mutations lead to a reduction in PDE10A levels in recombinant cellular systems, and critically, positron-emission-tomography (PET) studies with a specific PDE10A ligand confirmed that the p...
April 7, 2016: American Journal of Human Genetics
https://www.readbyqxmd.com/read/27009974/function-and-evolution-of-local-repeats-in-the-firre-locus
#17
Ezgi Hacisuleyman, Chinmay J Shukla, Catherine L Weiner, John L Rinn
More than half the human and mouse genomes are comprised of repetitive sequences, such as transposable elements (TEs), which have been implicated in many biological processes. In contrast, much less is known about other repeats, such as local repeats that occur in multiple instances within a given locus in the genome but not elsewhere. Here, we systematically characterize local repeats in the genomic locus of the Firre long noncoding RNA (lncRNA). We find a conserved function for the RRD repeat as a ribonucleic nuclear retention signal that is sufficient to retain an otherwise cytoplasmic mRNA in the nucleus...
March 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/26975529/integrative-analyses-reveal-a-long-noncoding-rna-mediated-sponge-regulatory-network-in-prostate-cancer
#18
Zhou Du, Tong Sun, Ezgi Hacisuleyman, Teng Fei, Xiaodong Wang, Myles Brown, John L Rinn, Mary Gwo-Shu Lee, Yiwen Chen, Philip W Kantoff, X Shirley Liu
Mounting evidence suggests that long noncoding RNAs (lncRNAs) can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts. However, the prevalence, functional significance and targets of lncRNA-mediated sponge regulation of cancer are mostly unknown. Here we identify a lncRNA-mediated sponge regulatory network that affects the expression of many protein-coding prostate cancer driver genes, by integrating analysis of sequence features and gene expression profiles of both lncRNAs and protein-coding genes in tumours...
March 15, 2016: Nature Communications
https://www.readbyqxmd.com/read/26883116/widespread-rna-binding-by-chromatin-associated-proteins
#19
David G Hendrickson, David R Kelley, Danielle Tenen, Bradley Bernstein, John L Rinn
BACKGROUND: Recent evidence suggests that RNA interaction can regulate the activity and localization of chromatin-associated proteins. However, it is unknown if these observations are specialized instances for a few key RNAs and chromatin factors in specific contexts, or a general mechanism underlying the establishment of chromatin state and regulation of gene expression. RESULTS: Here, we perform formaldehyde RNA immunoprecipitation (fRIP-Seq) to survey the RNA associated with a panel of 24 chromatin regulators and traditional RNA binding proteins...
February 16, 2016: Genome Biology
https://www.readbyqxmd.com/read/26832224/transcriptional-silencing-of-long-noncoding-rna-gng12-as1-uncouples-its-transcriptional-and-product-related-functions
#20
Lovorka Stojic, Malwina Niemczyk, Arturo Orjalo, Yoko Ito, Anna Elisabeth Maria Ruijter, Santiago Uribe-Lewis, Nimesh Joseph, Stephen Weston, Suraj Menon, Duncan T Odom, John Rinn, Fanni Gergely, Adele Murrell
Long noncoding RNAs (lncRNAs) regulate gene expression via their RNA product or through transcriptional interference, yet a strategy to differentiate these two processes is lacking. To address this, we used multiple small interfering RNAs (siRNAs) to silence GNG12-AS1, a nuclear lncRNA transcribed in an antisense orientation to the tumour-suppressor DIRAS3. Here we show that while most siRNAs silence GNG12-AS1 post-transcriptionally, siRNA complementary to exon 1 of GNG12-AS1 suppresses its transcription by recruiting Argonaute 2 and inhibiting RNA polymerase II binding...
February 2, 2016: Nature Communications
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