Chromatin Poises Mirna- and Protein-Coding Genes for Expression
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The Histone Methyltransferase DOT1L Prevents Antigen-Independent
bioRxiv preprint doi: https://doi.org/10.1101/826255; this version posted November 18, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+ T cells Eliza Mari Kwesi-Maliepaard1*, Muhammad Assad Aslam2,3*, Mir Farshid Alemdehy2*, Teun van den Brand4, Chelsea McLean1, Hanneke Vlaming1, Tibor van Welsem1, Tessy Korthout1, Cesare Lancini1, Sjoerd Hendriks1, Tomasz Ahrends5, Dieke van Dinther6, Joke M.M. den Haan6, Jannie Borst5, Elzo de Wit4, Fred van Leeuwen1,7,#, and Heinz Jacobs2,# 1Division of Gene Regulation, Netherlands Cancer Institute, 1066CX Amsterdam, The Netherlands 2Division of Tumor Biology & Immunology, Netherlands Cancer Institute, 1066CX Amsterdam, The Netherlands 3Institute of Molecular Biology and Biotechnology, Bahauddin Zakariya University, 60800 Multan, Pakistan 4Division of Gene Regulation, Netherlands Cancer Institute, 1066CX Amsterdam, and Oncode Institute, The Netherlands 5Division of Tumor Biology & Immunology, Netherlands Cancer Institute, 1066CX Amsterdam, and Oncode Institute, The Netherlands 6Department of Molecular Cell Biology and Immunology, Amsterdam UMC, Location VUmc, 1081HV Amsterdam, The Netherlands 7Department of Medical Biology, Amsterdam UMC, location AMC, UvA, 1105 AZ Amsterdam, The Netherlands * These authors contributed equally to this work. # Equal contribution and corresponding authors [email protected]; [email protected] Lead contact: Fred van Leeuwen 1 bioRxiv preprint doi: https://doi.org/10.1101/826255; this version posted November 18, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. -
The Diverse Functions of Dot1 and H3K79 Methylation
Downloaded from genesdev.cshlp.org on October 8, 2021 - Published by Cold Spring Harbor Laboratory Press REVIEW The diverse functions of Dot1 and H3K79 methylation Anh Tram Nguyen1,2 and Yi Zhang1,2,3 1Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA; 2Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA DOT1 (disruptor of telomeric silencing; also called ute to transcriptional regulation is to serve as a platform Kmt4) was initially discovered in budding yeast in a genetic for the recruitment of effector proteins. The well-studied screen for genes whose deletion confers defects in telo- lysine methylation residues include K4, K9, K27, K36, meric silencing. Since the discovery ~10 years ago that and K79 of histone H3, and K20 of histone H4. In general, Dot1 and its mammalian homolog, DOT1L (DOT1-Like), methylation at H3K9, H3K27, and H4K20 correlates with possess histone methyltransferase activity toward histone transcriptional repression, while methylation at H3K4, H3 Lys 79, great progress has been made in characterizing H3K36, and H3K79 correlates with gene transcription their enzymatic activities and the role of Dot1/DOT1L- (Kouzarides 2002; Peterson and Laniel 2004; Martin and mediated H3K79 methylation in transcriptional regula- Zhang 2005). In addition to its role in transcriptional tion, cell cycle regulation, and the DNA damage response. regulation, methylation has also been linked to X inacti- In addition, gene disruption in mice has revealed that vation, cell fate determination, terminal differentiation, mouse DOT1L plays an essential role in embryonic de- and the spatiotemporal patterning of Hox genes (Cavalli velopment, hematopoiesis, cardiac function, and the de- 2006; Minard et al. -
Dynamics of Transcription-Dependent H3k36me3 Marking by the SETD2:IWS1:SPT6 Ternary Complex
bioRxiv preprint doi: https://doi.org/10.1101/636084; this version posted May 14, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Dynamics of transcription-dependent H3K36me3 marking by the SETD2:IWS1:SPT6 ternary complex Katerina Cermakova1, Eric A. Smith1, Vaclav Veverka2, H. Courtney Hodges1,3,4,* 1 Department of Molecular & Cellular Biology, Center for Precision Environmental Health, and Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA 2 Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Prague, Czech Republic 3 Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA 4 Department of Bioengineering, Rice University, Houston, TX, 77005, USA * Lead contact; Correspondence to: [email protected] Abstract The genome-wide distribution of H3K36me3 is maintained SETD2 contributes to gene expression by marking gene through various mechanisms. In human cells, H3K36 is bodies with H3K36me3, which is thought to assist in the mono- and di-methylated by eight distinct histone concentration of transcription machinery at the small portion methyltransferases; however, the predominant writer of the of the coding genome. Despite extensive genome-wide data trimethyl mark on H3K36 is SETD21,11,12. Interestingly, revealing the precise localization of H3K36me3 over gene SETD2 is a major tumor suppressor in clear cell renal cell bodies, the physical basis for the accumulation, carcinoma13, breast cancer14, bladder cancer15, and acute maintenance, and sharp borders of H3K36me3 over these lymphoblastic leukemias16–18. In these settings, mutations sites remains rudimentary. -
16-0368 Technical Data Sheet
Nucleosome, Recombinant Human, H3K79me2 dNuc, Biotinylated Catalog No. 16-0368 Lot No. 19045001 Pack Size 50 µg Product Description: 1 2 Mononucleosomes assembled from recombinant human histones expressed in E. coli (two each of histones H2A, H2B, H3 and H4; accession numbers: H2A-P04908; H2B- O60814; H3.1-P68431; H4-P62805) wrapped by 147 base pairs of 601 positioning sequence DNA. Histone H3 (created by a proprietary synthetic method) contains dimethyl-lysine at position 79. The nucleosome is the basic subunit of chromatin. The 601 sequence, identified by Lowary and Widom, is a 147-base pair sequece that has high affinity for histone octamers and is useful for nucleosome assembly and contains a 5’ biotin-TEG group. Western Blot Data: Western Analysis of Nucleosome, Recombinant Human, H3K79me2. Top Panel: Unmodified H3 Formulation: (Lane 1) and H3K79me2 containing nucleosomes (Lane 2) were Nucleosome, Recombinant Human, H3K79me2 (27.3 µg probed with an anti-H3K79me2 antibody and analyzed via ECL protein weight, 50 µg total weight) in µl of 10 mM Tris readout. Only the H3K79me2sample produced a detectable signal. HCl, pH 7.5, 25 mM NaCl, 1 mM EDTA, 2 mM DTT, 20% Bottom Panel: Detailfrom Coomassie stained gel showing glycerol. unmodified nucleosomes (Lane 1) and H3K79me2 nucleosomes Molarity = μmolar. MW = Da. (Lane 2). Storage and Stability: Stable for six months at -80°C from date of receipt. For best results, aliquot and avoid multiple freeze/thaws. Application Notes: Nucleosome, Recombinant Human, H3K79me2 dNucs are highly purified and are suitable for use as substrates in enzyme screening assays or for effector protein binding experiments. -
Multi-Dimensional Genomic Analysis of Myoepithelial Carcinoma Identifies Prevalent Oncogenic Gene Fusions
ARTICLE DOI: 10.1038/s41467-017-01178-z OPEN Multi-dimensional genomic analysis of myoepithelial carcinoma identifies prevalent oncogenic gene fusions Martin G. Dalin1,2,3, Nora Katabi4, Marta Persson5, Ken-Wing Lee1, Vladimir Makarov1,6, Alexis Desrichard 1,6, Logan A. Walsh1, Lyndsay West7, Zaineb Nadeem1,7, Deepa Ramaswami1,7, Jonathan J. Havel1,6, Fengshen Kuo 1,6, Kalyani Chadalavada8, Gouri J. Nanjangud 8, Ian Ganly7, Nadeem Riaz6,9, Alan L. Ho10, Cristina R. Antonescu4, Ronald Ghossein4, Göran Stenman 5, Timothy A. Chan1,6,9 & Luc G.T. Morris 1,6,7 1234567890 Myoepithelial carcinoma (MECA) is an aggressive salivary gland cancer with largely unknown genetic features. Here we comprehensively analyze molecular alterations in 40 MECAs using integrated genomic analyses. We identify a low mutational load, and high prevalence (70%) of oncogenic gene fusions. Most fusions involve the PLAG1 oncogene, which is associated with PLAG1 overexpression. We find FGFR1-PLAG1 in seven (18%) cases, and the novel TGFBR3-PLAG1 fusion in six (15%) cases. TGFBR3-PLAG1 promotes a tumorigenic phenotype in vitro, and is absent in 723 other salivary gland tumors. Other novel PLAG1 fusions include ND4-PLAG1; a fusion between mitochondrial and nuclear DNA. We also identify higher number of copy number alterations as a risk factor for recurrence, independent of tumor stage at diagnosis. Our findings indicate that MECA is a fusion-driven disease, nominate TGFBR3-PLAG1 as a hallmark of MECA, and provide a framework for future diagnostic and therapeutic research in this lethal cancer. 1 Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. -
Le G´Enome En Action
LEGENOME´ EN ACTION SEQUENC´ ¸ AGE HAUT DEBIT´ ET EPIG´ ENOMIQUE´ Epig´enomique´ ? IFT6299 H2014 ? UdeM ? Mikl´osCs}ur¨os Regulation´ d’expression la transcription d’une region´ de l’ADN necessite´ ? liaisons proteine-ADN´ (facteur de transcription et son site reconnu) ? accessibilite´ de la chromatine REVIEWS Identification of regions that control transcription An initial step in the analysis of any gene is the identifi- cation of larger regions that might harbour regulatory control elements. Several advances have facilitated the prediction of such regions in the absence of knowl- edge about the specific characteristics of individual cis- Chromatin regulatory elements. These tools broadly fall into two categories: promoter (transcription start site; TSS) and enhancer detection. The methods are influenced Distal TFBS by sequence conservation between ORTHOLOGOUS genes (PHYLOGENETIC FOOTPRINTING), nucleotide composition and the assessment of available transcript data. Functional regulatory regions that control transcrip- tion rates tend to be proximal to the initiation site(s) of transcription. Although there is some circularity in the Co-activator complex data-collection process (regulatory sequences are sought near TSSs and are therefore found most often in these regions), the current set of laboratory-annotated regula- tory sequences indicates that sequences near a TSS are Transcription more likely to contain functionally important regulatory initiation complex Transcription controls than those that are more distal. However, specifi- initiation cation of the position of a TSS can be difficult. This is fur- ther complicated by the growing number of genes that CRM Proximal TFBS selectively use alternative start sites in certain contexts. Underlying most algorithms for promoter prediction is a Figure 1 | Components of transcriptional regulation. -
Complex Humoral Immune Response Against a Benign Tumor: Frequent Antibody Response Against Specific Antigens As Diagnostic Targets
Complex humoral immune response against a benign tumor: Frequent antibody response against specific antigens as diagnostic targets Nicole Comtesse*, Andrea Zippel*, Sascha Walle*, Dominik Monz*, Christina Backes*, Ulrike Fischer*, Jens Mayer*, Nicole Ludwig*, Andreas Hildebrandt†, Andreas Keller†, Wolf-Ingo Steudel‡, Hans-Peter Lenhof†, and Eckart Meese*§ *Department of Human Genetics, Medical School, University of Saarland, Building 60, 66421 Homburg͞Saar, Germany; ‡Department of Neurosurgery, Medical School, University of Saarland, Building 90, 66421 Homburg͞Saar, Germany; and †Department of Bioinformatics, University of Saarland, Building 36.1, 66041 Saarbru¨cken, Germany Edited by George Klein, Karolinska Institutet, Stockholm, Sweden, and approved May 16, 2005 (received for review January 17, 2005) There are numerous studies on the immune response against are likely attributed to overexpression of MGEA6͞11 protein in malignant human tumors. This study was aimed to address the tumor cells (12). complexity and specificity of humoral immune response against a Immunogenic tumor-associated antigens have been reported for benign human tumor. We assembled a panel of 62 meningioma- a large variety of malignant tumors, including melanomas and colon expressed antigens that show reactivity with serum antibodies of cancer. The finding of immunogenic antigens in meningioma leaves meningioma patients, including 41 previously uncharacterized an- several questions. Are benign tumors associated with a frequent tigens by screening of a fetal brain -
Modeling Circrnas Expression Pattern with Integrated Sequence And
bioRxiv preprint doi: https://doi.org/10.1101/392019; this version posted August 15, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Modeling circRNAs expression pattern with integrated sequence and 2 epigenetic features identifies H3K79me2 as regulators for circRNAs 3 expression 4 Jia-Bin Chen1#, Shan-Shan Dong1#, Shi Yao1, Yuan-Yuan Duan1, Wei-Xin Hu1, Hao 5 Chen1, Nai-Ning Wang1, Ruo-Han Hao1, Ming-Rui Guo1, Yu-Jie Zhang1, Yu Rong1, Yi- 6 Xiao Chen1, Hlaing Nwe Thynn1, Fu-Ling Zhou2, Yan Guo1*, Tie-Lin Yang1* 7 8 Running title: Exploring circRNAs expression regulatory mechanism 9 10 1Key Laboratory of Biomedical Information Engineering of Ministry of Education, 11 School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P. R. 12 China 13 2Department of Hematopathology, Zhongnan Hospital of Wuhan University, Wuhan 14 430071, P. R. China 15 16 #These authors contribute equally to this work. 17 The authors wish it to be known that, in their opinion, the first 2 authors should be 18 regarded as joint First Authors 19 20 *Corresponding Authors: 21 Tie-Lin Yang, Ph.D. 22 Key Laboratory of Biomedical Information Engineering of Ministry of Education, 23 School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, P. R. 24 China 25 Tel: 86-29-82668463 1 bioRxiv preprint doi: https://doi.org/10.1101/392019; this version posted August 15, 2018. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. -
Nº Ref Uniprot Proteína Péptidos Identificados Por MS/MS 1 P01024
Document downloaded from http://www.elsevier.es, day 26/09/2021. This copy is for personal use. Any transmission of this document by any media or format is strictly prohibited. Nº Ref Uniprot Proteína Péptidos identificados 1 P01024 CO3_HUMAN Complement C3 OS=Homo sapiens GN=C3 PE=1 SV=2 por 162MS/MS 2 P02751 FINC_HUMAN Fibronectin OS=Homo sapiens GN=FN1 PE=1 SV=4 131 3 P01023 A2MG_HUMAN Alpha-2-macroglobulin OS=Homo sapiens GN=A2M PE=1 SV=3 128 4 P0C0L4 CO4A_HUMAN Complement C4-A OS=Homo sapiens GN=C4A PE=1 SV=1 95 5 P04275 VWF_HUMAN von Willebrand factor OS=Homo sapiens GN=VWF PE=1 SV=4 81 6 P02675 FIBB_HUMAN Fibrinogen beta chain OS=Homo sapiens GN=FGB PE=1 SV=2 78 7 P01031 CO5_HUMAN Complement C5 OS=Homo sapiens GN=C5 PE=1 SV=4 66 8 P02768 ALBU_HUMAN Serum albumin OS=Homo sapiens GN=ALB PE=1 SV=2 66 9 P00450 CERU_HUMAN Ceruloplasmin OS=Homo sapiens GN=CP PE=1 SV=1 64 10 P02671 FIBA_HUMAN Fibrinogen alpha chain OS=Homo sapiens GN=FGA PE=1 SV=2 58 11 P08603 CFAH_HUMAN Complement factor H OS=Homo sapiens GN=CFH PE=1 SV=4 56 12 P02787 TRFE_HUMAN Serotransferrin OS=Homo sapiens GN=TF PE=1 SV=3 54 13 P00747 PLMN_HUMAN Plasminogen OS=Homo sapiens GN=PLG PE=1 SV=2 48 14 P02679 FIBG_HUMAN Fibrinogen gamma chain OS=Homo sapiens GN=FGG PE=1 SV=3 47 15 P01871 IGHM_HUMAN Ig mu chain C region OS=Homo sapiens GN=IGHM PE=1 SV=3 41 16 P04003 C4BPA_HUMAN C4b-binding protein alpha chain OS=Homo sapiens GN=C4BPA PE=1 SV=2 37 17 Q9Y6R7 FCGBP_HUMAN IgGFc-binding protein OS=Homo sapiens GN=FCGBP PE=1 SV=3 30 18 O43866 CD5L_HUMAN CD5 antigen-like OS=Homo -
The Human Gene Connectome As a Map of Short Cuts for Morbid Allele Discovery
The human gene connectome as a map of short cuts for morbid allele discovery Yuval Itana,1, Shen-Ying Zhanga,b, Guillaume Vogta,b, Avinash Abhyankara, Melina Hermana, Patrick Nitschkec, Dror Friedd, Lluis Quintana-Murcie, Laurent Abela,b, and Jean-Laurent Casanovaa,b,f aSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065; bLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Paris Descartes University, Institut National de la Santé et de la Recherche Médicale U980, Necker Medical School, 75015 Paris, France; cPlateforme Bioinformatique, Université Paris Descartes, 75116 Paris, France; dDepartment of Computer Science, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel; eUnit of Human Evolutionary Genetics, Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, Institut Pasteur, F-75015 Paris, France; and fPediatric Immunology-Hematology Unit, Necker Hospital for Sick Children, 75015 Paris, France Edited* by Bruce Beutler, University of Texas Southwestern Medical Center, Dallas, TX, and approved February 15, 2013 (received for review October 19, 2012) High-throughput genomic data reveal thousands of gene variants to detect a single mutated gene, with the other polymorphic genes per patient, and it is often difficult to determine which of these being of less interest. This goes some way to explaining why, variants underlies disease in a given individual. However, at the despite the abundance of NGS data, the discovery of disease- population level, there may be some degree of phenotypic homo- causing alleles from such data remains somewhat limited. geneity, with alterations of specific physiological pathways under- We developed the human gene connectome (HGC) to over- come this problem. -
The Human Gene Connectome As a Map of Short Cuts for Morbid Allele Discovery
The human gene connectome as a map of short cuts for morbid allele discovery Yuval Itana,1, Shen-Ying Zhanga,b, Guillaume Vogta,b, Avinash Abhyankara, Melina Hermana, Patrick Nitschkec, Dror Friedd, Lluis Quintana-Murcie, Laurent Abela,b, and Jean-Laurent Casanovaa,b,f aSt. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY 10065; bLaboratory of Human Genetics of Infectious Diseases, Necker Branch, Paris Descartes University, Institut National de la Santé et de la Recherche Médicale U980, Necker Medical School, 75015 Paris, France; cPlateforme Bioinformatique, Université Paris Descartes, 75116 Paris, France; dDepartment of Computer Science, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel; eUnit of Human Evolutionary Genetics, Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, Institut Pasteur, F-75015 Paris, France; and fPediatric Immunology-Hematology Unit, Necker Hospital for Sick Children, 75015 Paris, France Edited* by Bruce Beutler, University of Texas Southwestern Medical Center, Dallas, TX, and approved February 15, 2013 (received for review October 19, 2012) High-throughput genomic data reveal thousands of gene variants to detect a single mutated gene, with the other polymorphic genes per patient, and it is often difficult to determine which of these being of less interest. This goes some way to explaining why, variants underlies disease in a given individual. However, at the despite the abundance of NGS data, the discovery of disease- population level, there may be some degree of phenotypic homo- causing alleles from such data remains somewhat limited. geneity, with alterations of specific physiological pathways under- We developed the human gene connectome (HGC) to over- come this problem. -
Synthetic Histone Code
Available online at www.sciencedirect.com ScienceDirect Synthetic histone code 1 2 3 Wolfgang Fischle , Henning D Mootz and Dirk Schwarzer Chromatin is the universal template of genetic information in all copies each of the core histones H2A, H2B, H3, and H4 eukaryotic cells. This complex of DNA and histone proteins not and one copy of linker histone H1, Figure 1a) [1]. By only packages and organizes genomes but also regulates gene various levels of folding, the originating primary chroma- expression. A multitude of posttranslational histone tin fiber can be organized into various structural arrange- modifications and their combinations are thought to constitute ments, including highly condensed mitotic chromosomes a code for directing distinct structural and functional states of (Figure 1b). While the basic architecture of nucleosomes chromatin. Methods of protein chemistry, including protein is the same throughout the genome, posttranslational semisynthesis, amber suppression technology, and cysteine modifications (PTMs) of histones are central means of bioconjugation, have enabled the generation of so-called increasing the biochemical divergence that regulates designer chromatin containing histones in defined and chromatin structure and function [2,3]. Histone PTMs homogeneous modification states. Several of these are structurally diverse and include methylation, acetyla- approaches have matured from proof-of-concept studies into tion and ubiquitinylation of lysine, as well as phosphor- efficient tools and technologies for studying the biochemistry of ylation of serine and threonine residues (Figure 1c). More chromatin regulation and for interrogating the histone code. We than 150 histone modification sites have been identified summarize pioneering experiments and recent developments in different experimental systems.