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YAP1 subgroup supratentorial ependymoma requires TEAD and nuclear factor I-mediated transcriptional programmes for tumorigenesis.

Kristian W Pajtler | Yiju Wei | Konstantin Okonechnikov | Patricia B G Silva | Mikaella Vouri | Lei Zhang | Sebastian Brabetz | Laura Sieber | Melissa Gulley | Monika Mauermann | Tatjana Wedig | Norman Mack | Yuka Imamura Kawasawa | Tanvi Sharma | Marc Zuckermann | Felipe Andreiuolo | Eric Holland | Kendra Maass | Huiqin Körkel-Qu | Hai-Kun Liu | Felix Sahm | David Capper | Jens Bunt | Linda J Richards | David T W Jones | Andrey Korshunov | Lukas Chavez | Peter Lichter | Mikio Hoshino | Stefan M Pfister | Marcel Kool | Wei Li | Daisuke Kawauchi
Nature communications | 2019

YAP1 fusion-positive supratentorial ependymomas predominantly occur in infants, but the molecular mechanisms of oncogenesis are unknown. Here we show YAP1-MAMLD1 fusions are sufficient to drive malignant transformation in mice, and the resulting tumors share histo-molecular characteristics of human ependymomas. Nuclear localization of YAP1-MAMLD1 protein is mediated by MAMLD1 and independent of YAP1-Ser127 phosphorylation. Chromatin immunoprecipitation-sequencing analyses of human YAP1-MAMLD1-positive ependymoma reveal enrichment of NFI and TEAD transcription factor binding site motifs in YAP1-bound regulatory elements, suggesting a role for these transcription factors in YAP1-MAMLD1-driven tumorigenesis. Mutation of the TEAD binding site in the YAP1 fusion or repression of NFI targets prevents tumor induction in mice. Together, these results demonstrate that the YAP1-MAMLD1 fusion functions as an oncogenic driver of ependymoma through recruitment of TEADs and NFIs, indicating a rationale for preclinical studies to block the interaction between YAP1 fusions and NFI and TEAD transcription factors.

Pubmed ID: 31477715

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This is a list of tools and resources that we have found mentioned in this publication.


Covance (tool)

RRID:SCR_001224

A contract research organization providing drug development and animal testing services. Under the name Covance Research Products Inc., based in Denver, Pennsylvania, the company also deals in the import, breeding and sale of laboratory animals. It breeds dogs, rabbits, guinea pigs, non-human primates, and pigs, and runs the largest non-human primate laboratory in Germany. (Wikipedia)

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ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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DAVID (tool)

RRID:SCR_001881

Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.

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Addgene (tool)

RRID:SCR_002037

Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.

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ImageJ (tool)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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Systems Transcriptional Activity Reconstruction (tool)

RRID:SCR_005622

A next-generation web-based application that aims to provide an integrated solution for both visualization and analysis of deep-sequencing data, along with simple access to public datasets.

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REViGO (tool)

RRID:SCR_005825

Web server that summarizes lists of Gene Ontology terms by removing redundant terms and visualizing the remaining ones in scatterplots, interactive graphs, treemaps, or tag clouds. Platform: Online tool

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BEDTools (tool)

RRID:SCR_006646

A powerful toolset for genome arithmetic allowing one to address common genomics tasks such as finding feature overlaps and computing coverage. Bedtools allows one to intersect, merge, count, complement, and shuffle genomic intervals from multiple files in widely-used genomic file formats such as BAM, BED, GFF/GTF, VCF. While each individual tool is designed to do a relatively simple task (e.g., intersect two interval files), quite sophisticated analyses can be conducted by combining multiple bedtools operations on the UNIX command line.

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ENCODE (tool)

RRID:SCR_006793

Encyclopedia of DNA elements consisting of list of functional elements in human genome, including elements that act at protein and RNA levels, and regulatory elements that control cells and circumstances in which gene is active. Enables scientific and medical communities to interpret role of human genome in biology and disease. Provides identification of common cell types to facilitate integrative analysis and new experimental technologies based on high-throughput sequencing. Genome Browser containing ENCODE and Epigenomics Roadmap data. Data are available for entire human genome.

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QIAGEN (tool)

RRID:SCR_008539

A commercial organization which provides assay technologies to isolate DNA, RNA, and proteins from any biological sample. Assay technologies are then used to make specific target biomolecules, such as the DNA of a specific virus, visible for subsequent analysis.

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Millipore (tool)

RRID:SCR_008983

An Antibody supplier

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Sigma-Aldrich (tool)

RRID:SCR_008988

American chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.

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Subread (tool)

RRID:SCR_009803

Software package for high-performance read alignment, quantification and mutation discovery.General purpose read aligner which can be used to map both genomic DNA-seq reads and RNA-seq reads. Subread aligner as fast, accurate and scalable read mapping by seed-and-vote.These programs were also implemented in Bioconductor R package Rsubread.

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HOMER (tool)

RRID:SCR_010881

Software tools for Motif Discovery and next-gen sequencing analysis. Used for analyzing ChIP-Seq, GRO-Seq, RNA-Seq, DNase-Seq, Hi-C and numerous other types of functional genomics sequencing data sets. Collection of command line programs for unix style operating systems written in Perl and C++.

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LIMMA (tool)

RRID:SCR_010943

Software package for the analysis of gene expression microarray data, especially the use of linear models for analyzing designed experiments and the assessment of differential expression.

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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Abcam (tool)

RRID:SCR_012931

A commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.

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NIH 3T3 (tool)

RRID:CVCL_0594

Cell line NIH 3T3 is a Spontaneously immortalized cell line with a species of origin Mus musculus

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HEK293T (tool)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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LN-229 (tool)

RRID:CVCL_0393

Cell line LN-229 is a Cancer cell line with a species of origin Homo sapiens (Human)

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Crl:CD1(ICR) (tool)

RRID:IMSR_CRL:022

Mus musculus with name Crl:CD1(ICR) from IMSR.

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HEK293T (tool)

RRID:CVCL_0063

Cell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)

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