HIST1H2AC (Human) Recombinant Protein (Q01)

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HIST1H2AC (Human) Recombinant Protein (Q01) Catalog # : H00008334-Q01 規格 : [ 10 ug ] [ 25 ug ] List All Specification Application Image Product Human HIST1H2AC partial ORF ( NP_003503, 25 a.a. - 96 a.a.) Enzyme-linked Immunoabsorbent Assay Description: recombinant protein with GST-tag at N-terminal. Western Blot (Recombinant Sequence: QFPVGRVHRLLRKGNYAERVGAGAPVYLAAVLEYLTAEILELAGNAARD protein) NKKTRIIPRHLQLAIRNDEELNK Antibody Production Host: Wheat Germ (in vitro) Protein Array Theoretical MW 33.66 (kDa): Preparation in vitro wheat germ expression system Method: Purification: Glutathione Sepharose 4 Fast Flow Quality Control 12.5% SDS-PAGE Stained with Coomassie Blue. Testing: Storage Buffer: 50 mM Tris-HCI, 10 mM reduced Glutathione, pH=8.0 in the elution buffer. Storage Store at -80°C. Aliquot to avoid repeated freezing and thawing. Instruction: Note: Best use within three months from the date of receipt of this protein. MSDS: Download Datasheet: Download Applications Enzyme-linked Immunoabsorbent Assay Western Blot (Recombinant protein) Antibody Production Protein Array Page 1 of 2 2016/5/22 Gene Information Entrez GeneID: 8334 GeneBank NM_003512 Accession#: Protein NP_003503 Accession#: Gene Name: HIST1H2AC Gene Alias: H2A/l,H2AFL,MGC99519,dJ221C16.4 Gene histone cluster 1, H2ac Description: Omim ID: 602794 Gene Ontology: Hyperlink Gene Summary: Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a member of the histone H2A family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq Other H2A histone family, member L,OTTHUMP00000016145,histone 1, Designations: H2ac,histone H2AC Gene Pathway Systemic lupus erythematosus 服務條款 | 隱私權政策 | 著作及商標 | 網站地圖 ©2016 亞諾法生技股份有限公司 Abnova Corporation. 版權所有. Page 2 of 2 2016/5/22.

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Histone Isoform H2A1H Promotes Attainment of Distinct Physiological
Bhattacharya et al. Epigenetics & Chromatin (2017) 10:48 DOI 10.1186/s13072-017-0155-z Epigenetics & Chromatin RESEARCH Open Access Histone isoform H2A1H promotes attainment of distinct physiological states by altering chromatin dynamics Saikat Bhattacharya1,4,6, Divya Reddy1,4, Vinod Jani5†, Nikhil Gadewal3†, Sanket Shah1,4, Raja Reddy2,4, Kakoli Bose2,4, Uddhavesh Sonavane5, Rajendra Joshi5 and Sanjay Gupta1,4* Abstract Background: The distinct functional efects of the replication-dependent histone H2A isoforms have been dem- onstrated; however, the mechanistic basis of the non-redundancy remains unclear. Here, we have investigated the specifc functional contribution of the histone H2A isoform H2A1H, which difers from another isoform H2A2A3 in the identity of only three amino acids. Results: H2A1H exhibits varied expression levels in diferent normal tissues and human cancer cell lines (H2A1C in humans). It also promotes cell proliferation in a context-dependent manner when exogenously overexpressed. To uncover the molecular basis of the non-redundancy, equilibrium unfolding of recombinant H2A1H-H2B dimer was performed. We found that the M51L alteration at the H2A–H2B dimer interface decreases the temperature of melting of H2A1H-H2B by ~ 3 °C as compared to the H2A2A3-H2B dimer. This diference in the dimer stability is also refected in the chromatin dynamics as H2A1H-containing nucleosomes are more stable owing to M51L and K99R substitu- tions. Molecular dynamic simulations suggest that these substitutions increase the number of hydrogen bonds and hydrophobic interactions of H2A1H, enabling it to form more stable nucleosomes. Conclusion: We show that the M51L and K99R substitutions, besides altering the stability of histone–histone and histone–DNA complexes, have the most prominent efect on cell proliferation, suggesting that the nucleosome sta- bility is intimately linked with the physiological efects observed.
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HIST1H2AC Human Shrna Plasmid Kit (Locus ID 8334) Product Data
OriGene Technologies, Inc. 9620 Medical Center Drive, Ste 200 Rockville, MD 20850, US Phone: +1-888-267-4436 [email protected] EU: [email protected] CN: [email protected] Product datasheet for TL312444 HIST1H2AC Human shRNA Plasmid Kit (Locus ID 8334) Product data: Product Type: shRNA Plasmids Product Name: HIST1H2AC Human shRNA Plasmid Kit (Locus ID 8334) Locus ID: 8334 Synonyms: dJ221C16.4; H2A/l; H2AFL; HIST1H2AC Vector: pGFP-C-shLenti (TR30023) Format: Lentiviral plasmids Components: HIST1H2AC - Human, 4 unique 29mer shRNA constructs in lentiviral GFP vector(Gene ID = 8334). 5µg purified plasmid DNA per construct Non-effective 29-mer scrambled shRNA cassette in pGFP-C-shLenti Vector, TR30021, included for free. RefSeq: NM_003512, NM_003512.1, NM_003512.2, NM_003512.3, BC085010, BC017379, BC050602, NM_003512.4 Summary: Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H2A family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6. [provided by RefSeq, Aug 2015] shRNA Design: These shRNA constructs were designed against multiple splice variants at this gene locus.
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Mutational Landscape of Uterine and Ovarian Carcinosarcomas Implicates Histone Genes in Epithelial–Mesenchymal Transition
Mutational landscape of uterine and ovarian carcinosarcomas implicates histone genes in epithelial–mesenchymal transition Siming Zhaoa,b, Stefania Bellonec, Salvatore Lopezc, Durga Thakrala,b, Carlton Schwabc, Diana P. Englishc, Jonathan Blackc, Emiliano Coccoc, Jungmin Choia,b, Luca Zammataroc, Federica Predolinic, Elena Bonazzolic, Mark Bia,b, Natalia Buzad, Pei Huid, Serena Wongd, Maysa Abu-Khalafe, Antonella Ravaggif, Eliana Bignottif, Elisabetta Bandieraf, Chiara Romanif, Paola Todeschinif, Renata Tassif, Laura Zanottif, Franco Odicinof, Sergio Pecorellif, Carla Donzellig, Laura Ardighierig, Fabio Facchettig, Marcella Falchettig, Dan-Arin Silasic, Elena Ratnerc, Masoud Azodic, Peter E. Schwartzc, Shrikant Manea,b, Roberto Angiolih, Corrado Terranovah, Charles Matthew Quicki, Babak Edrakij, Kaya Bilgüvara,b, Moses Leek, Murim Choik, Amy L. Stieglerl, Titus J. Boggonl, Joseph Schlessingerl, Richard P. Liftona,b,m,1, and Alessandro D. Santinc aDepartment of Genetics, Yale University School of Medicine, New Haven, CT 06510; bHoward Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510; cDepartment of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06510; dDepartment of Pathology, Yale University School of Medicine, New Haven, CT 06510; eInternal Medicine & Oncology, Yale University School of Medicine, New Haven, CT 06510; f“Angelo Nocivelli” Institute of Molecular Medicine, Department of Obstetrics & Gynecology, University of Brescia, 25100 Brescia, Italy;
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Histone-Related Genes Are Hypermethylated in Lung Cancer
Published OnlineFirst October 1, 2019; DOI: 10.1158/0008-5472.CAN-19-1019 Cancer Genome and Epigenome Research Histone-Related Genes Are Hypermethylated in Lung Cancer and Hypermethylated HIST1H4F Could Serve as a Pan-Cancer Biomarker Shihua Dong1,Wei Li1, Lin Wang2, Jie Hu3,Yuanlin Song3, Baolong Zhang1, Xiaoguang Ren1, Shimeng Ji3, Jin Li1, Peng Xu1, Ying Liang1, Gang Chen4, Jia-Tao Lou2, and Wenqiang Yu1 Abstract Lung cancer is the leading cause of cancer-related deaths lated in all 17 tumor types from TCGA datasets (n ¼ 7,344), worldwide. Cytologic examination is the current "gold stan- which was further validated in nine different types of cancer dard" for lung cancer diagnosis, however, this has low sensi- (n ¼ 243). These results demonstrate that HIST1H4F can tivity. Here, we identified a typical methylation signature of function as a universal-cancer-only methylation (UCOM) histone genes in lung cancer by whole-genome DNA methyl- marker, which may aid in understanding general tumorigen- ation analysis, which was validated by The Cancer Genome esis and improve screening for early cancer diagnosis. Atlas (TCGA) lung cancer cohort (n ¼ 907) and was further confirmed in 265 bronchoalveolar lavage fluid samples with Significance: These findings identify a new biomarker for specificity and sensitivity of 96.7% and 87.0%, respectively. cancer detection and show that hypermethylation of histone- More importantly, HIST1H4F was universally hypermethy- related genes seems to persist across cancers. Introduction to its low specificity, LDCT is far from satisfactory as a screening tool for clinical application, similar to other currently used cancer Lung cancer is one of the most common malignant tumors and biomarkers, such as carcinoembryonic antigen (CEA), neuron- the leading cause of cancer-related deaths worldwide (1, 2).
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WNT16 Is a New Marker of Senescence
Table S1. A. Complete list of 177 genes overexpressed in replicative senescence Value Gene Description UniGene RefSeq 2.440 WNT16 wingless-type MMTV integration site family, member 16 (WNT16), transcript variant 2, mRNA. Hs.272375 NM_016087 2.355 MMP10 matrix metallopeptidase 10 (stromelysin 2) (MMP10), mRNA. Hs.2258 NM_002425 2.344 MMP3 matrix metallopeptidase 3 (stromelysin 1, progelatinase) (MMP3), mRNA. Hs.375129 NM_002422 2.300 HIST1H2AC Histone cluster 1, H2ac Hs.484950 2.134 CLDN1 claudin 1 (CLDN1), mRNA. Hs.439060 NM_021101 2.119 TSPAN13 tetraspanin 13 (TSPAN13), mRNA. Hs.364544 NM_014399 2.112 HIST2H2BE histone cluster 2, H2be (HIST2H2BE), mRNA. Hs.2178 NM_003528 2.070 HIST2H2BE histone cluster 2, H2be (HIST2H2BE), mRNA. Hs.2178 NM_003528 2.026 DCBLD2 discoidin, CUB and LCCL domain containing 2 (DCBLD2), mRNA. Hs.203691 NM_080927 2.007 SERPINB2 serpin peptidase inhibitor, clade B (ovalbumin), member 2 (SERPINB2), mRNA. Hs.594481 NM_002575 2.004 HIST2H2BE histone cluster 2, H2be (HIST2H2BE), mRNA. Hs.2178 NM_003528 1.989 OBFC2A Oligonucleotide/oligosaccharide-binding fold containing 2A Hs.591610 1.962 HIST2H2BE histone cluster 2, H2be (HIST2H2BE), mRNA. Hs.2178 NM_003528 1.947 PLCB4 phospholipase C, beta 4 (PLCB4), transcript variant 2, mRNA. Hs.472101 NM_182797 1.934 PLCB4 phospholipase C, beta 4 (PLCB4), transcript variant 1, mRNA. Hs.472101 NM_000933 1.933 KRTAP1-5 keratin associated protein 1-5 (KRTAP1-5), mRNA. Hs.534499 NM_031957 1.894 HIST2H2BE histone cluster 2, H2be (HIST2H2BE), mRNA. Hs.2178 NM_003528 1.884 CYTL1 cytokine-like 1 (CYTL1), mRNA. Hs.13872 NM_018659 tumor necrosis factor receptor superfamily, member 10d, decoy with truncated death domain (TNFRSF10D), 1.848 TNFRSF10D Hs.213467 NM_003840 mRNA.
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Genome-Wide Transcriptional Analysis of Carboplatin Response in Chemosensitive and Chemoresistant Ovarian Cancer Cells
1605 Genome-wide transcriptional analysis of carboplatin response in chemosensitive and chemoresistant ovarian cancer cells David Peters,1,2 John Freund,2 and Robert L. Ochs2 variety of disease processes, including cancer. Patterns of global gene expression can reveal the molecular pathways 1 Department of Pharmacology and Therapeutics, University of relevant to the disease process and identify potential new Liverpool, United Kingdom and 2Precision Therapeutics, Inc., Pittsburgh, Pennsylvania therapeutic targets. The use of this technology for the molecular classification of cancer was recently shown with the identification of an expression profile that was Abstract predictive of patient outcome for B-cell lymphoma (1). We have recently described an ex vivo chemoresponse In addition, this study showed that histologically similar assay for determining chemosensitivity in primary cultures tumors can be differentiated based on their gene expression of human tumors. In this study, we have extended these profiles. Ultimately, these unique patterns of gene expres- experiments in an effort to correlate chemoresponse data sion may be used as guidelines to direct different modes of with gene expression patterns at the level of transcription. therapy. Primary cultures of cells derived from ovarian carcinomas Although it is widely recognized that patients with the of individual patients (n = 6) were characterized using same histologic stage and grade of cancer respond to the ChemoFx assay and classified as either carboplatin therapies differently, few clinical tests can predict indi- sensitive (n = 3) or resistant (n = 3). Three representa- vidual patient responses. The next great challenge will be tive cultures of cells from each individual tumor were then to use the power of post-genomic technology, including subjected to Affymetrix gene chip analysis (n = 18) using microarray analyses, to correlate gene expression patterns U95A human gene chip arrays.
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Targeting the DEK Oncogene in Head and Neck Squamous Cell Carcinoma: Functional and Transcriptional Consequences
Targeting the DEK oncogene in head and neck squamous cell carcinoma: functional and transcriptional consequences A dissertation submitted to the Graduate School of the University of Cincinnati in partial fulfillment of the requirements to the degree of Doctor of Philosophy (Ph.D.) in the Department of Cancer and Cell Biology of the College of Medicine March 2015 by Allie Kate Adams B.S. The Ohio State University, 2009 Dissertation Committee: Susanne I. Wells, Ph.D. (Chair) Keith A. Casper, M.D. Peter J. Stambrook, Ph.D. Ronald R. Waclaw, Ph.D. Susan E. Waltz, Ph.D. Kathryn A. Wikenheiser-Brokamp, M.D., Ph.D. Abstract Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignancies worldwide with over 50,000 new cases in the United States each year. For many years tobacco and alcohol use were the main etiological factors; however, it is now widely accepted that human papillomavirus (HPV) infection accounts for at least one-quarter of all HNSCCs. HPV+ and HPV- HNSCCs are studied as separate diseases as their prognosis, treatment, and molecular signatures are distinct. Five-year survival rates of HNSCC hover around 40-50%, and novel therapeutic targets and biomarkers are necessary to improve patient outcomes. Here, we investigate the DEK oncogene and its function in regulating HNSCC development and signaling. DEK is overexpressed in many cancer types, with roles in molecular processes such as transcription, DNA repair, and replication, as well as phenotypes such as apoptosis, senescence, and proliferation. DEK had never been previously studied in this tumor type; therefore, our studies began with clinical specimens to examine DEK expression patterns in primary HNSCC tissue.
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Human Papillomavirus Oncoprotein E7 Dysregulates Immune
HUMAN PAPILLOMAVIRUS ONCOPROTEIN E7 DYSREGULATES IMMUNE RESPONSES THROUGH EPIGENETIC MANIPULATION by LOUIS J CICCHINI B.S., University of Arizona, 2009 A thesis submitted to the Faculty of the Graduate School of the University of Colorado in partial fulfillment of the requirements for the degree of Doctor of Philosophy Molecular Biology 2016 This thesis for the Doctor of Philosophy degree by Louis J Cicchini has been approved for the Molecular Biology Program by Rytis Prekeris, Chair Dohun Pyeon, Advisor James Hagman Thomas E. Morrison Xiao-Jing Wang Date: August 18, 2016 ii Cicchini, Louis J. (PhD, Molecular Biology) Human Papillomavirus Oncoprotein E7 Dysregulates Immune Responses through Epigenetic Manipulation Thesis directed by Associate Professor Dohun Pyeon ABSTRACT High-risk human papillomaviruses (HPVs) are causally associated with multiple human cancers. Previous studies have shown that the HPV oncoprotein E7 induces immune suppression; however, the underlying mechanisms remain unknown. We report that, while expression of many proinflammatory chemokines increases throughout HPV-positive cancer progression, CXCL14 is dramatically downregulated by promoter hypermethylation in an E7- dependent manner. Our in vivo mouse models revealed that restoration of Cxcl14 expression in HPV-positive mouse oropharyngeal carcinoma cells clears tumors in immunocompetent syngeneic mice, but not in Rag1-deficient mice. Further, restoration of Cxcl14 expression significantly increases natural killer (NK), CD4+ T, and CD8+ T cell infiltration into the tumor-draining lymph nodes in vivo. In vitro transwell migration assays show that restoration of Cxcl14 expression induces chemotaxis of NK, CD4+ T, and CD8+ T cells. These findings suggest that high-risk HPV E7 is likely to dysregulate host gene expression in order to persist by modulating host DNA methylation.
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Functionally Distinct Roles for Replication-Dependent Histone H2A Isoforms in Cell Proliferation and Carcinogenesis Rajbir Singh1, Amir Mortazavi2, Kelly H
9284–9295 Nucleic Acids Research, 2013, Vol. 41, No. 20 Published online 16 August 2013 doi:10.1093/nar/gkt736 NAR Breakthrough Article Increasing the complexity of chromatin: functionally distinct roles for replication-dependent histone H2A isoforms in cell proliferation and carcinogenesis Rajbir Singh1, Amir Mortazavi2, Kelly H. Telu3, Prabakaran Nagarajan1, David M. Lucas2, Jennifer M. Thomas-Ahner2, Steven K. Clinton2, John C. Byrd2, Michael A. Freitas4 and Mark R. Parthun1,* 1Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, OH 43210, USA, 2Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA, 3Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA, 4Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA Received June 21, 2013; Revised July 22, 2013; Accepted July 25, 2013 ABSTRACT nucleosome consists of 147 base pairs of DNA wrapped around a protein complex called the histone Replication-dependent histones are encoded by octamer that contains two molecules of each of the four multigene families found in several large clusters in core histones (H2A, H2B, H3 and H4). The importance of the human genome and are thought to be functionally chromatin structure for the packaging and regulation of redundant. However, the abundance of specific rep- eukaryotic genomes is evidenced by the extraordinary con- lication-dependent isoforms of histone H2A is altered servation of this structure throughout eukaryotic evolu- in patients with chronic lymphocytic leukemia. Similar tion. The core histones are among the most highly changes in the abundance of H2A isoforms are also conserved eukaryotic proteins with many residues being associated with the proliferation and tumorigenicity completely invariant (1).
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Genomic Insights Into the Pathogenesis of Epstein–Barr Virus
Gebauer et al. Blood Cancer Journal (2021) 11:102 https://doi.org/10.1038/s41408-021-00493-5 Blood Cancer Journal ARTICLE Open Access Genomic insights into the pathogenesis of Epstein–Barr virus-associated diffuse large B-cell lymphoma by whole-genome and targeted amplicon sequencing Niklas Gebauer 1,2,AxelKünstner 2,3,4, Julius Ketzer1,2,5,HannoM.Witte 1,2,6,TobiasRausch 7, Vladimir Benes 7, Jürgen Zimmermann7,JudithGebauer2,8,HartmutMerz9,VeronicaBernard9, Lana Harder10,KatharinaRatjen10, Stefan Gesk10,WolfgangPeter11,12, Yannik Busch11, Peter Trojok11, Nikolas von Bubnoff 1,2, Harald Biersack1,2, Hauke Busch2,3,4 and Alfred C. Feller9 Abstract Epstein–Barr virus (EBV)-associated diffuse large B-cell lymphoma not otherwise specified (DLBCL NOS) constitute a distinct clinicopathological entity in the current World Health Organization (WHO) classification. However, its genomic features remain sparsely characterized. Here, we combine whole-genome sequencing (WGS), targeted amplicon sequencing (tNGS), and fluorescence in situ hybridization (FISH) from 47 EBV + DLBCL (NOS) cases to delineate the genomic landscape of this rare disease. Integrated WGS and tNGS analysis clearly distinguished this tumor type from EBV-negative DLBCL due to frequent mutations in ARID1A (45%), KMT2A/KMT2D (32/30%), ANKRD11 (32%), or NOTCH2 (32%). WGS uncovered structural aberrations including 6q deletions (5/8 patients), which were subsequently validated 1234567890():,; 1234567890():,; 1234567890():,; 1234567890():,; by FISH (14/32 cases). Expanding on previous reports, we identified recurrent alterations in CCR6 (15%), DAPK1 (15%), TNFRSF21 (13%), CCR7 (11%), and YY1 (6%). Lastly, functional annotation of the mutational landscape by sequential gene set enrichment and network propagation predicted an effect on the nuclear factor κB (NFκB) pathway (CSNK2A2, CARD10), IL6/JAK/STAT (SOCS1/3, STAT3), and WNT signaling (FRAT1, SFRP5) alongside aberrations in immunological processes, such as interferon response.
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Mechanism of Progression in Cervical Intraepithelial Neoplasia
Università degli Studi di Ferrara DOTTORATO DI RICERCA IN SCIENZE BIOMEDICHE CICLO XXVII COORDINATORE Prof. Silvano Capitani Mechanism of progression in cervical intraepithelial neoplasia Settore Scientifico Disciplinare BIO/13 Dottorando Tutore Dott. John Charles Rotondo Prof. Mauro Tognon Anni 2012/2014 INDEX INTRODUCTION 3 OBJECTIVE AND AIMS OF THE STUDY 25 MATERIALS AND METHODS 26 RESULTS 36 DISCUSSION 58 REFERENCES 68 2 INTRODUCTION CERVICAL INTRAEPITHELIAL NEOPLASIA Classification of the cervical intraepithelial neoplasia The cervical intraepithelial neoplasia (CIN) is a pre-cancerous lesion of uterine cervical squamous cell carcinoma (SCC) and is characterized by potentially premalignant transformation and abnormal growth, named dysplasia, of cervical keratinocytes. The histological classification system provides three CIN grades referred to as CIN1 (mild dysplasia), CIN2 (moderate dysplasia) and CIN3 (severe dysplasia) lesions. Each CIN grade remains confined to the cervical epithelium (Figure 1, A, www.lookfordiagnosis.com) and has a variable potential evolution towards the cancer. CIN1 lesions are characterized by keratinocytes with abnormal cell growth, perinuclear cytoplasmic vacuolation, named koilocytosis, and increase volume of the nucleus. This histologic change is confined to the basal third of the cervical epithelium (Figure 1, B). CIN2 lesions, compared to CIN1, are characterized by higher cytologic atypia and cellular disorganization, while koilocytosis is lower or absent. The histological abnormalities are confined to the basal two thirds of the cervical epithelium (Figure 1, C). CIN2 cervical cells show two main features: (i) atypical mitotic figures induced by aneuploidy; (ii) abnormal nucleus/cytoplasm ratio. CIN3 lesions are characterized by keratinocytes endowed with high proliferative index, immaturity and vertical orientation. Abnormal keratinocytes exceed the two thirds of the epithelium or expand throughout the thickness of the epithelium, altering the whole cyto-architecture of the tissue (Figure 1, D).
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Viral Integration Transforms Chromatin to Drive Oncogenesis
bioRxiv preprint doi: https://doi.org/10.1101/2020.02.12.942755; this version posted September 3, 2020. 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. Viral integration transforms chromatin to drive oncogenesis Mehran Karimzadeh (ORCID: 0000-0002-7324-6074)1,2,3, Christopher Arlidge (ORCID: 0000-0001-9454-8541)2, Ariana Rostami (ORCID: 0000-0002-3423-8303)1,2, Mathieu Lupien (ORCID: 0000-0003-0929-9478)1,2,5, Scott V. Bratman (ORCID: 0000-0001-8610-4908)1,2,5, and Michael M. Hoffman (ORCID: 0000-0002-4517-1562)1,2,3,4,5 1Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada 2Princess Margaret Cancer Centre, Toronto, ON, Canada 3Vector Institute, Toronto, ON, Canada 4Department of Computer Science, University of Toronto, Toronto, ON, Canada 5Lead contact: [email protected], [email protected], [email protected] September 1, 2020 Abstract Human papillomavirus (HPV) drives almost all cervical cancers and up to 70% of head and neck cancers. Frequent integration into the host genome occurs only for tumourigenic strains of HPV.We hypothesized that changes in the epigenome and transcriptome contribute to the tumourigenicity∼ of HPV. We found that viral integration events often occurred along with changes in chromatin state and expression of genes near the integration site. We investigated whether introduction of new transcription factor binding sites due to HPV integration could invoke these changes. Some regions within the HPV genome, particularly the position of a conserved CTCF sequence motif, showed enriched chromatin accessibility signal.
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