A Single Allele of Hdac2 but Not Hdac1 Is Sufficient for Normal Mouse Brain
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Screening and Identification of Key Biomarkers in Clear Cell Renal Cell Carcinoma Based on Bioinformatics Analysis
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder.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. Screening and identification of key biomarkers in clear cell renal cell carcinoma based on bioinformatics analysis Basavaraj Vastrad1, Chanabasayya Vastrad*2 , Iranna Kotturshetti 1. Department of Biochemistry, Basaveshwar College of Pharmacy, Gadag, Karnataka 582103, India. 2. Biostatistics and Bioinformatics, Chanabasava Nilaya, Bharthinagar, Dharwad 580001, Karanataka, India. 3. Department of Ayurveda, Rajiv Gandhi Education Society`s Ayurvedic Medical College, Ron, Karnataka 562209, India. * Chanabasayya Vastrad [email protected] Ph: +919480073398 Chanabasava Nilaya, Bharthinagar, Dharwad 580001 , Karanataka, India bioRxiv preprint doi: https://doi.org/10.1101/2020.12.21.423889; this version posted December 23, 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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder.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. Abstract Clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignancy of the urinary system. The pathogenesis and effective diagnosis of ccRCC have become popular topics for research in the previous decade. In the current study, an integrated bioinformatics analysis was performed to identify core genes associated in ccRCC. An expression dataset (GSE105261) was downloaded from the Gene Expression Omnibus database, and included 26 ccRCC and 9 normal kideny samples. Assessment of the microarray dataset led to the recognition of differentially expressed genes (DEGs), which was subsequently used for pathway and gene ontology (GO) enrichment analysis. -
Mapping Influenza-Induced Posttranslational Modifications On
viruses Article Mapping Influenza-Induced Posttranslational Modifications on Histones from CD8+ T Cells Svetlana Rezinciuc 1, Zhixin Tian 2, Si Wu 2, Shawna Hengel 2, Ljiljana Pasa-Tolic 2 and Heather S. Smallwood 1,3,* 1 Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN 38163, USA; [email protected] 2 Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99354, USA; [email protected] (Z.T.); [email protected] (S.W.); [email protected] (S.H.); [email protected] (L.P.-T.) 3 Children’s Foundation Research Institute, Memphis, TN 38105, USA * Correspondence: [email protected]; Tel.: +1-(901)-448–3068 Academic Editor: Italo Tempera Received: 10 October 2020; Accepted: 2 December 2020; Published: 8 December 2020 Abstract: T cell function is determined by transcriptional networks that are regulated by epigenetic programming via posttranslational modifications (PTMs) to histone proteins and DNA. Bottom-up mass spectrometry (MS) can identify histone PTMs, whereas intact protein analysis by MS can detect species missed by bottom-up approaches. We used a novel approach of online two-dimensional liquid chromatography-tandem MS with high-resolution reversed-phase liquid chromatography (RPLC), alternating electron transfer dissociation (ETD) and collision-induced dissociation (CID) on precursor ions to maximize fragmentation of uniquely modified species. The first online RPLC separation sorted histone families, then RPLC or weak cation exchange hydrophilic interaction liquid chromatography (WCX-HILIC) separated species heavily clad in PTMs. Tentative identifications were assigned by matching proteoform masses to predicted theoretical masses that were verified with tandem MS. We used this innovative approach for histone-intact protein PTM mapping (HiPTMap) to identify and quantify proteoforms purified from CD8 T cells after in vivo influenza infection. -
SF3B3) and Sin3a Associated Protein 130 (SAP130
cells Communication Ambiguity about Splicing Factor 3b Subunit 3 (SF3B3) and Sin3A Associated Protein 130 (SAP130) Paula I. Metselaar 1,* , Celine Hos 1, Olaf Welting 1, Jos A. Bosch 2,3, Aletta D. Kraneveld 4 , Wouter J. de Jonge 1 and Anje A. Te Velde 1 1 Tytgat Institute for Liver and Intestinal Research, AGEM, Amsterdam UMC, University of Amsterdam, 1105BK Amsterdam, The Netherlands; [email protected] (C.H.); [email protected] (O.W.); [email protected] (W.J.d.J.); [email protected] (A.A.T.V.) 2 Department of Psychology, University of Amsterdam, 1018WS Amsterdam, The Netherlands; [email protected] 3 Department of Medical Psychology, Amsterdam UMC, University of Amsterdam, 1001NK Amsterdam, The Netherlands 4 Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584CG Utrecht, The Netherlands; [email protected] * Correspondence: [email protected] Abstract: In 2020, three articles were published on a protein that can activate the immune system by binding to macrophage-inducible C-type lectin receptor (Mincle). In the articles, the protein was referred to as ‘SAP130, a subunit of the histone deacetylase complex.’ However, the Mincle ligand the authors aimed to investigate is splicing factor 3b subunit 3 (SF3B3). This splicing factor is unrelated to SAP130 (Sin3A associated protein 130, a subunit of the histone deacetylase-dependent Sin3A corepressor complex). The conclusions in the three articles were formulated for SF3B3, Citation: Metselaar, P.I.; Hos, C.; while the researchers used qPCR primers and antibodies against SAP130. -
Mediator of DNA Damage Checkpoint 1 (MDC1) Is a Novel Estrogen Receptor Co-Regulator in Invasive 6 Lobular Carcinoma of the Breast 7 8 Evelyn K
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.16.423142; this version posted December 16, 2020. 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 4.0 International license. 1 Running Title: MDC1 co-regulates ER in ILC 2 3 Research article 4 5 Mediator of DNA damage checkpoint 1 (MDC1) is a novel estrogen receptor co-regulator in invasive 6 lobular carcinoma of the breast 7 8 Evelyn K. Bordeaux1+, Joseph L. Sottnik1+, Sanjana Mehrotra1, Sarah E. Ferrara2, Andrew E. Goodspeed2,3, James 9 C. Costello2,3, Matthew J. Sikora1 10 11 +EKB and JLS contributed equally to this project. 12 13 Affiliations 14 1Dept. of Pathology, University of Colorado Anschutz Medical Campus 15 2Biostatistics and Bioinformatics Shared Resource, University of Colorado Comprehensive Cancer Center 16 3Dept. of Pharmacology, University of Colorado Anschutz Medical Campus 17 18 Corresponding author 19 Matthew J. Sikora, PhD.; Mail Stop 8104, Research Complex 1 South, Room 5117, 12801 E. 17th Ave.; Aurora, 20 CO 80045. Tel: (303)724-4301; Fax: (303)724-3712; email: [email protected]. Twitter: 21 @mjsikora 22 23 Authors' contributions 24 MJS conceived of the project. MJS, EKB, and JLS designed and performed experiments. JLS developed models 25 for the project. EKB, JLS, SM, and AEG contributed to data analysis and interpretation. SEF, AEG, and JCC 26 developed and performed informatics analyses. MJS wrote the draft manuscript; all authors read and revised the 27 manuscript and have read and approved of this version of the manuscript. -
Exogenous Hydrogen Sulfide Plays an Important Role by Regulating
International Journal of Molecular Sciences Review Exogenous Hydrogen Sulfide Plays an Important Role by Regulating Autophagy in Diabetic-Related Diseases Shuangyu Lv , Huiyang Liu and Honggang Wang * Henan International Joint Laboratory of Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng 475000, China; [email protected] (S.L.); [email protected] (H.L.) * Correspondence: [email protected] Abstract: Autophagy is a vital cell mechanism which plays an important role in many physiological processes including clearing long-lived, accumulated and misfolded proteins, removing damaged organelles and regulating growth and aging. Autophagy also participates in a variety of biological functions, such as development, cell differentiation, resistance to pathogens and nutritional hunger. Recently, autophagy has been reported to be involved in diabetes, but the mechanism is not fully understood. Hydrogen sulfide (H2S) is a colorless, water-soluble, flammable gas with the typical odor of rotten eggs, which has been known as a highly toxic gas for many years. However, it has been reported recently that H2S, together with nitric oxide and carbon monoxide, is an important gas signal transduction molecule. H2S has been reported to play a protective role in many diabetes- related diseases, but the mechanism is not fully clear. Recent studies indicate that H2S plays an important role by regulating autophagy in many diseases including cancer, tissue fibrosis diseases and glycometabolic diseases; however, the related mechanism has not been fully studied. In this review, we summarize recent research on the role of H2S in regulating autophagy in diabetic-related diseases to provide references for future related research. -
Subcellular Distribution of HDAC1 in Neurotoxic Conditions Is Dependent on Serine Phosphorylation
The Journal of Neuroscience, August 2, 2017 • 37(31):7547–7559 • 7547 Neurobiology of Disease Subcellular Distribution of HDAC1 in Neurotoxic Conditions Is Dependent on Serine Phosphorylation Yunjiao Zhu,1* Oscar G. Vidaurre,1* XKadidia P. Adula,1 XNebojsa Kezunovic,1 XMaureen Wentling,1 X George W. Huntley,1 and XPatrizia Casaccia1,2 1Department of Neuroscience, Friedman Brain Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York 10029, and 2Advanced Science Research Center at the Graduate Center of the City University of New York, New York, New York 10031 Calcium-dependent nuclear export of histone deacetylase 1 (HDAC1) was shown previously to precede axonal damage in culture, but the in vivo relevance of these findings and the potential posttranslational modifications of HDAC1 remained elusive. Using acute hippocam- pal slices from mice of either sex with genetic conditional ablation of Hdac1 in CA1 hippocampal neurons (i.e., Camk2a-cre;Hdac1 fl/fl), we show significantly diminished axonal damage in response to neurotoxic stimuli. The protective effect of Hdac1 ablation was detected also in CA3 neurons in Grik4-cre;Hdac1 fl/f mice, which were more resistant to the excitotoxic damage induced by intraventricular injection of kainic acid. The amino acid residues modulating HDAC1 subcellular localization were identified by site-directed mutagenesis, which identified serine residues 421 and 423 as critical for its nuclear localization. The physiological phosphorylation of HDAC1 was decreased by neurotoxic stimuli, which stimulated the phosphatase enzymatic activity of calcineurin. Treatment of neurons with the calcineurin inhibitors FK506 or cyclosporin A resulted in nuclear accumulation of phospho-HDAC1 and was neuroprotective. -
Determining HDAC8 Substrate Specificity by Noah Ariel Wolfson A
Determining HDAC8 substrate specificity by Noah Ariel Wolfson A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy (Biological Chemistry) in the University of Michigan 2014 Doctoral Committee: Professor Carol A. Fierke, Chair Professor Robert S. Fuller Professor Anna K. Mapp Associate Professor Patrick J. O’Brien Associate Professor Raymond C. Trievel Dedication My thesis is dedicated to all my family, mentors, and friends who made getting to this point possible. ii Table of Contents Dedication ....................................................................................................................................... ii List of Figures .............................................................................................................................. viii List of Tables .................................................................................................................................. x List of Appendices ......................................................................................................................... xi Abstract ......................................................................................................................................... xii Chapter 1 HDAC8 substrates: Histones and beyond ...................................................................... 1 Overview ..................................................................................................................................... 1 HDAC introduction -
Loss of Fam60a, a Sin3a Subunit, Results in Embryonic Lethality and Is Associated with Aberrant Methylation at a Subset of Gene
RESEARCH ARTICLE Loss of Fam60a, a Sin3a subunit, results in embryonic lethality and is associated with aberrant methylation at a subset of gene promoters Ryo Nabeshima1,2, Osamu Nishimura3,4, Takako Maeda1, Natsumi Shimizu2, Takahiro Ide2, Kenta Yashiro1†, Yasuo Sakai1, Chikara Meno1, Mitsutaka Kadota3,4, Hidetaka Shiratori1†, Shigehiro Kuraku3,4*, Hiroshi Hamada1,2* 1Developmental Genetics Group, Graduate School of Frontier Biosciences, Osaka University, Suita, Japan; 2Laboratory for Organismal Patterning, RIKEN Center for Developmental Biology, Kobe, Japan; 3Phyloinformatics Unit, RIKEN Center for Life Science Technologies, Kobe, Japan; 4Laboratory for Phyloinformatics, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan Abstract We have examined the role of Fam60a, a gene highly expressed in embryonic stem cells, in mouse development. Fam60a interacts with components of the Sin3a-Hdac transcriptional corepressor complex, and most Fam60a–/– embryos manifest hypoplasia of visceral organs and die in utero. Fam60a is recruited to the promoter regions of a subset of genes, with the expression of these genes being either up- or down-regulated in Fam60a–/– embryos. The DNA methylation level of the Fam60a target gene Adhfe1 is maintained at embryonic day (E) 7.5 but markedly reduced at –/– *For correspondence: E9.5 in Fam60a embryos, suggesting that DNA demethylation is enhanced in the mutant. [email protected] (SK); Examination of genome-wide DNA methylation identified several differentially methylated regions, [email protected] (HH) which were preferentially hypomethylated, in Fam60a–/– embryos. Our data suggest that Fam60a is †These authors contributed required for proper embryogenesis, at least in part as a result of its regulation of DNA methylation equally to this work at specific gene promoters. -
Cellular and Molecular Signatures in the Disease Tissue of Early
Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of -
Up-Regulation of UVRAG by HDAC1 Inhibition Attenuates 5FU-Induced
ANTICANCER RESEARCH 38 : 271-277 (2018) doi:10.21873/anticanres.12218 Up-regulation of UVRAG by HDAC1 Inhibition Attenuates 5FU-induced Cell Death in HCT116 Colorectal Cancer Cells YOON KYUNG JO 1* , NA YEON PARK 1* , JI HYUN SHIN 1, DOO SIN JO 1, JI-EUN BAE 1, EUN SUN CHOI 1, SUNGHO MAENG 1, HONG BAE JEON 2, SEON AE ROH 3, JONG WOOK CHANG 4, JIN CHEON KIM 3,5 and DONG-HYUNG CHO 1 1Department of Gerontology, Graduate School of East-West Medical Science, Kyung Hee University, Seoul, Republic of Korea; 2Biomedical Research Institute, MEDIPOST Corporation, Seongnam, Republic of Korea; 3Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea; 4Stem Cell & Regenerative Medicine Institute, Samsung Medical Center, Seoul, Republic of Korea; 5Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea Abstract. The ultraviolent irradiation resistance-associated Autophagy has important roles in cellular homeostasis gene (UVRAG), a component of the Beclin 1/autophagy- through the degradation of useless or damaged proteins and related 6 complex, regulates the autophagy initiation step organelles via lysosomes (1, 2). The primordial function of and functions in the DNA-damage response. UVRAG is autophagy is a response to stress, such as starvation, frequently mutated in various cancer types, and mutations of oxidative stress, and ion stress (1, 2). Given that multiple UVRAG increase sensitivity to chemotherapy by impairing signaling pathways are involved in the regulation of DNA-damage repair. In this study, we addressed the autophagy progress, various autophagy-related (ATG) epigenetic regulation of UVRAG in colorectal cancer cells. -
A Role for Mammalian Sin3 in Permanent Gene Silencing
Molecular Cell Article A Role for Mammalian Sin3 in Permanent Gene Silencing Chris van Oevelen,1 Jinhua Wang,1 Patrik Asp,1 Qin Yan,2,3 William G. Kaelin, Jr.,2,3 Yuval Kluger,1,* and Brian David Dynlacht1,* 1New York University School of Medicine, NYU Cancer Institute, 522 1st Avenue, New York, NY 10016, USA 2Howard Hughes Medical Institute 3Department of Medical Oncology Dana Farber Cancer Institute and Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA *Correspondence: [email protected] (B.D.D.), [email protected] (Y.K.) DOI 10.1016/j.molcel.2008.10.015 SUMMARY substoichiometric regulatory proteins, including Swi/Snf-remod- eling proteins, retinoblastoma (RB)-binding protein 2 (RBP2), and The multisubunit Sin3 corepressor complex regu- other proteins (Hayakawa et al., 2007; Nagl et al., 2007; Sif et al., lates gene transcription through deacetylation of nu- 2001). Interestingly, RBP2 was recently shown to be a demethy- cleosomes. However, the full range of Sin3 activities lase specific for di- and trimethylated lysine 4 of histone H3 and targets is not well understood. Here, we have (Christensen et al., 2007; Klose et al., 2007). Thus, the Sin3 investigated genome-wide binding of mouse Sin3 complex provides a versatile platform for chromatin modifying and RBP2 as well as histone modifications and nucle- and remodeling activities. Sin3/Rpd3 corepressor complexes are recruited to promoter osome positioning as a function of myogenic differ- regions via sequence-specific repressors such as Ume6 or entiation. Remarkably, we find that Sin3 complexes Mad in yeast and mammalian cells, respectively, resulting in spread immediately downstream of the transcription localized deacetylation of histones within promoter regions and start site on repressed and transcribed genes during transcriptional silencing (Ayer et al., 1995; Kadosh and Struhl, differentiation. -
Small-Molecule Suppressors of Cytokine-Induced Beta-Cell Apoptosis
Small-Molecule Suppressors of Cytokine-Induced Beta-Cell Apoptosis The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Chou, Danny Hung-Chieh. 2011. Small-Molecule Suppressors of Cytokine-Induced Beta-Cell Apoptosis. Doctoral dissertation, Harvard University. Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:10121978 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA © 2011- Hung-Chieh Chou All rights reserved. Professor Stuart Schreiber Danny Hung-Chieh Chou Small-molecule suppressors of cytokine-induced beta-cell apoptosis Abstract Type-1 diabetes is caused by the autoimmune destruction of insulin-producing beta cells in the pancreas. Beta-cell apoptosis involves a complex set of signaling cascades initiated by interleukin-1 (IL-1), interferon- (IFN-), and tumor necrosis factor- (TNF- ). IL-1 and TNF- induce NFB expression, while IFN- induces STAT1 activation. These cytokines lead to a decrease of beta-cell function. The goal of this thesis is to identify small-molecule suppressors of cytokine-induced beta-cell apoptosis using high- throughput screening approach. Using the rat INS-1E beta-cell line, I developed an assay to measure cellular viability after 48 hours of cytokine treatment. I screened 29,760 compounds for their ability to suppress the negative effects of the cytokines. I identified several compounds to be suppressors of beta-cell apoptosis.