A Caspase-2-RFXANK Interaction and Its Implication for MHC Class II
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CIITA Stimulation of Transcription Factor Binding to Major Histocompatibility Complex Class II and Associated Promoters in Vivo
Proc. Natl. Acad. Sci. USA Vol. 95, pp. 6267–6272, May 1998 Genetics CIITA stimulation of transcription factor binding to major histocompatibility complex class II and associated promoters in vivo i KENNETH L. WRIGHT*†§,KEH-CHUANG CHIN‡§¶,MICHAEL LINHOFF*, CHERYL SKINNER*, JEFFREY A. BROWN , i JEREMY M. BOSS ,GEORGE R. STARK**, AND JENNY P.-Y. TING*†† *Lineberger Comprehensive Cancer Center and the Department of Immunology and Microbiology, and ‡Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599; iDepartment of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and **Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195 Contributed by George R. Stark, March 12, 1998 ABSTRACT CIITA is a master transactivator of the ma- RFX5 (14). However, the mode of action of CIITA and its in jor histocompatibility complex class II genes, which are vivo target have remained elusive. involved in antigen presentation. Defects in CIITA result in Changes in promoter assembly or proteinyDNA interactions fatal immunodeficiencies. CIITA activation is also the control can be detected in intact cells by in vivo genomic footprinting point for the induction of major histocompatibility complex (15). Analysis of the DRA promoter by this technique has class II and associated genes by interferon-g, but CIITA does revealed interactions at promoter-proximal transcription fac- not bind directly to DNA. Expression of CIITA in G3A cells, tor binding sites X and Y in both B lymphocytes and IFN-g- which lack endogenous CIITA, followed by in vivo genomic treated cells (16, 17). The Ii and DMB promoters show similar footprinting, now reveals that CIITA is required for the interactions at the their X and Y sites (18–20). -
Significant Shortest Paths for the Detection of Putative Disease Modules
bioRxiv preprint doi: https://doi.org/10.1101/2020.04.01.019844; this version posted April 2, 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 The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.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-ND 4.0 International license. SIGNIFICANT SHORTEST PATHS FOR THE DETECTION OF PUTATIVE DISEASE MODULES Daniele Pepe1 1Department of Oncology, KU Leuven, LKI–Leuven Cancer Institute, Leuven, Belgium Email address: DP: [email protected] bioRxiv preprint doi: https://doi.org/10.1101/2020.04.01.019844; this version posted April 2, 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-ND 4.0 International license. Keywords Structural equation modeling, significant shortest paths, pathway analysis, disease modules. Abstract Background The characterization of diseases in terms of perturbated gene modules was recently introduced for the analysis of gene expression data. Some approaches were proposed in literature, but many times they are inductive approaches. This means that starting directly from data, they try to infer key gene networks potentially associated to the biological phenomenon studied. However they ignore the biological information already available to characterize the gene modules. Here we propose the detection of perturbed gene modules using the combination of data driven and hypothesis-driven approaches relying on biological metabolic pathways and significant shortest paths tested by structural equation modeling. -
RFXANK Mouse Monoclonal Antibody [Clone ID: OTI3C10] – TA504261
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 TA504261 RFXANK Mouse Monoclonal Antibody [Clone ID: OTI3C10] Product data: Product Type: Primary Antibodies Clone Name: OTI3C10 Applications: FC, IF, IHC, WB Recommended Dilution: WB 1:500, IHC 1:150, IF 1:100, FLOW 1:100 Reactivity: Human, Mouse, Rat Host: Mouse Isotype: IgG1 Clonality: Monoclonal Immunogen: Full length human recombinant protein of human RFXANK(NP_604389) produced in HEK293T cell. Formulation: PBS (PH 7.3) containing 1% BSA, 50% glycerol and 0.02% sodium azide. Concentration: 1 mg/ml Purification: Purified from mouse ascites fluids or tissue culture supernatant by affinity chromatography (protein A/G) Conjugation: Unconjugated Storage: Store at -20°C as received. Stability: Stable for 12 months from date of receipt. Predicted Protein Size: 25.4 kDa Gene Name: regulatory factor X associated ankyrin containing protein Database Link: NP_604389 Entrez Gene 8625 Human O14593 This product is to be used for laboratory only. Not for diagnostic or therapeutic use. View online » ©2021 OriGene Technologies, Inc., 9620 Medical Center Drive, Ste 200, Rockville, MD 20850, US 1 / 3 RFXANK Mouse Monoclonal Antibody [Clone ID: OTI3C10] – TA504261 Background: Major histocompatibility (MHC) class II molecules are transmembrane proteins that have a central role in development and control of the immune system. The protein encoded by this gene, along with regulatory factor X-associated protein and regulatory factor-5, forms a complex that binds to the X box motif of certain MHC class II gene promoters and activates their transcription. -
A Computational Approach for Defining a Signature of Β-Cell Golgi Stress in Diabetes Mellitus
Page 1 of 781 Diabetes A Computational Approach for Defining a Signature of β-Cell Golgi Stress in Diabetes Mellitus Robert N. Bone1,6,7, Olufunmilola Oyebamiji2, Sayali Talware2, Sharmila Selvaraj2, Preethi Krishnan3,6, Farooq Syed1,6,7, Huanmei Wu2, Carmella Evans-Molina 1,3,4,5,6,7,8* Departments of 1Pediatrics, 3Medicine, 4Anatomy, Cell Biology & Physiology, 5Biochemistry & Molecular Biology, the 6Center for Diabetes & Metabolic Diseases, and the 7Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202; 2Department of BioHealth Informatics, Indiana University-Purdue University Indianapolis, Indianapolis, IN, 46202; 8Roudebush VA Medical Center, Indianapolis, IN 46202. *Corresponding Author(s): Carmella Evans-Molina, MD, PhD ([email protected]) Indiana University School of Medicine, 635 Barnhill Drive, MS 2031A, Indianapolis, IN 46202, Telephone: (317) 274-4145, Fax (317) 274-4107 Running Title: Golgi Stress Response in Diabetes Word Count: 4358 Number of Figures: 6 Keywords: Golgi apparatus stress, Islets, β cell, Type 1 diabetes, Type 2 diabetes 1 Diabetes Publish Ahead of Print, published online August 20, 2020 Diabetes Page 2 of 781 ABSTRACT The Golgi apparatus (GA) is an important site of insulin processing and granule maturation, but whether GA organelle dysfunction and GA stress are present in the diabetic β-cell has not been tested. We utilized an informatics-based approach to develop a transcriptional signature of β-cell GA stress using existing RNA sequencing and microarray datasets generated using human islets from donors with diabetes and islets where type 1(T1D) and type 2 diabetes (T2D) had been modeled ex vivo. To narrow our results to GA-specific genes, we applied a filter set of 1,030 genes accepted as GA associated. -
4-6 Weeks Old Female C57BL/6 Mice Obtained from Jackson Labs Were Used for Cell Isolation
Methods Mice: 4-6 weeks old female C57BL/6 mice obtained from Jackson labs were used for cell isolation. Female Foxp3-IRES-GFP reporter mice (1), backcrossed to B6/C57 background for 10 generations, were used for the isolation of naïve CD4 and naïve CD8 cells for the RNAseq experiments. The mice were housed in pathogen-free animal facility in the La Jolla Institute for Allergy and Immunology and were used according to protocols approved by the Institutional Animal Care and use Committee. Preparation of cells: Subsets of thymocytes were isolated by cell sorting as previously described (2), after cell surface staining using CD4 (GK1.5), CD8 (53-6.7), CD3ε (145- 2C11), CD24 (M1/69) (all from Biolegend). DP cells: CD4+CD8 int/hi; CD4 SP cells: CD4CD3 hi, CD24 int/lo; CD8 SP cells: CD8 int/hi CD4 CD3 hi, CD24 int/lo (Fig S2). Peripheral subsets were isolated after pooling spleen and lymph nodes. T cells were enriched by negative isolation using Dynabeads (Dynabeads untouched mouse T cells, 11413D, Invitrogen). After surface staining for CD4 (GK1.5), CD8 (53-6.7), CD62L (MEL-14), CD25 (PC61) and CD44 (IM7), naïve CD4+CD62L hiCD25-CD44lo and naïve CD8+CD62L hiCD25-CD44lo were obtained by sorting (BD FACS Aria). Additionally, for the RNAseq experiments, CD4 and CD8 naïve cells were isolated by sorting T cells from the Foxp3- IRES-GFP mice: CD4+CD62LhiCD25–CD44lo GFP(FOXP3)– and CD8+CD62LhiCD25– CD44lo GFP(FOXP3)– (antibodies were from Biolegend). In some cases, naïve CD4 cells were cultured in vitro under Th1 or Th2 polarizing conditions (3, 4). -
A Flexible Microfluidic System for Single-Cell Transcriptome Profiling
www.nature.com/scientificreports OPEN A fexible microfuidic system for single‑cell transcriptome profling elucidates phased transcriptional regulators of cell cycle Karen Davey1,7, Daniel Wong2,7, Filip Konopacki2, Eugene Kwa1, Tony Ly3, Heike Fiegler2 & Christopher R. Sibley 1,4,5,6* Single cell transcriptome profling has emerged as a breakthrough technology for the high‑resolution understanding of complex cellular systems. Here we report a fexible, cost‑efective and user‑ friendly droplet‑based microfuidics system, called the Nadia Instrument, that can allow 3′ mRNA capture of ~ 50,000 single cells or individual nuclei in a single run. The precise pressure‑based system demonstrates highly reproducible droplet size, low doublet rates and high mRNA capture efciencies that compare favorably in the feld. Moreover, when combined with the Nadia Innovate, the system can be transformed into an adaptable setup that enables use of diferent bufers and barcoded bead confgurations to facilitate diverse applications. Finally, by 3′ mRNA profling asynchronous human and mouse cells at diferent phases of the cell cycle, we demonstrate the system’s ability to readily distinguish distinct cell populations and infer underlying transcriptional regulatory networks. Notably this provided supportive evidence for multiple transcription factors that had little or no known link to the cell cycle (e.g. DRAP1, ZKSCAN1 and CEBPZ). In summary, the Nadia platform represents a promising and fexible technology for future transcriptomic studies, and other related applications, at cell resolution. Single cell transcriptome profling has recently emerged as a breakthrough technology for understanding how cellular heterogeneity contributes to complex biological systems. Indeed, cultured cells, microorganisms, biopsies, blood and other tissues can be rapidly profled for quantifcation of gene expression at cell resolution. -
ATP-Binding and Hydrolysis in Inflammasome Activation
molecules Review ATP-Binding and Hydrolysis in Inflammasome Activation Christina F. Sandall, Bjoern K. Ziehr and Justin A. MacDonald * Department of Biochemistry & Molecular Biology, Cumming School of Medicine, University of Calgary, 3280 Hospital Drive NW, Calgary, AB T2N 4Z6, Canada; [email protected] (C.F.S.); [email protected] (B.K.Z.) * Correspondence: [email protected]; Tel.: +1-403-210-8433 Academic Editor: Massimo Bertinaria Received: 15 September 2020; Accepted: 3 October 2020; Published: 7 October 2020 Abstract: The prototypical model for NOD-like receptor (NLR) inflammasome assembly includes nucleotide-dependent activation of the NLR downstream of pathogen- or danger-associated molecular pattern (PAMP or DAMP) recognition, followed by nucleation of hetero-oligomeric platforms that lie upstream of inflammatory responses associated with innate immunity. As members of the STAND ATPases, the NLRs are generally thought to share a similar model of ATP-dependent activation and effect. However, recent observations have challenged this paradigm to reveal novel and complex biochemical processes to discern NLRs from other STAND proteins. In this review, we highlight past findings that identify the regulatory importance of conserved ATP-binding and hydrolysis motifs within the nucleotide-binding NACHT domain of NLRs and explore recent breakthroughs that generate connections between NLR protein structure and function. Indeed, newly deposited NLR structures for NLRC4 and NLRP3 have provided unique perspectives on the ATP-dependency of inflammasome activation. Novel molecular dynamic simulations of NLRP3 examined the active site of ADP- and ATP-bound models. The findings support distinctions in nucleotide-binding domain topology with occupancy of ATP or ADP that are in turn disseminated on to the global protein structure. -
Association of Gene Ontology Categories with Decay Rate for Hepg2 Experiments These Tables Show Details for All Gene Ontology Categories
Supplementary Table 1: Association of Gene Ontology Categories with Decay Rate for HepG2 Experiments These tables show details for all Gene Ontology categories. Inferences for manual classification scheme shown at the bottom. Those categories used in Figure 1A are highlighted in bold. Standard Deviations are shown in parentheses. P-values less than 1E-20 are indicated with a "0". Rate r (hour^-1) Half-life < 2hr. Decay % GO Number Category Name Probe Sets Group Non-Group Distribution p-value In-Group Non-Group Representation p-value GO:0006350 transcription 1523 0.221 (0.009) 0.127 (0.002) FASTER 0 13.1 (0.4) 4.5 (0.1) OVER 0 GO:0006351 transcription, DNA-dependent 1498 0.220 (0.009) 0.127 (0.002) FASTER 0 13.0 (0.4) 4.5 (0.1) OVER 0 GO:0006355 regulation of transcription, DNA-dependent 1163 0.230 (0.011) 0.128 (0.002) FASTER 5.00E-21 14.2 (0.5) 4.6 (0.1) OVER 0 GO:0006366 transcription from Pol II promoter 845 0.225 (0.012) 0.130 (0.002) FASTER 1.88E-14 13.0 (0.5) 4.8 (0.1) OVER 0 GO:0006139 nucleobase, nucleoside, nucleotide and nucleic acid metabolism3004 0.173 (0.006) 0.127 (0.002) FASTER 1.28E-12 8.4 (0.2) 4.5 (0.1) OVER 0 GO:0006357 regulation of transcription from Pol II promoter 487 0.231 (0.016) 0.132 (0.002) FASTER 6.05E-10 13.5 (0.6) 4.9 (0.1) OVER 0 GO:0008283 cell proliferation 625 0.189 (0.014) 0.132 (0.002) FASTER 1.95E-05 10.1 (0.6) 5.0 (0.1) OVER 1.50E-20 GO:0006513 monoubiquitination 36 0.305 (0.049) 0.134 (0.002) FASTER 2.69E-04 25.4 (4.4) 5.1 (0.1) OVER 2.04E-06 GO:0007050 cell cycle arrest 57 0.311 (0.054) 0.133 (0.002) -
UNIVERSITY of CALIFORNIA RIVERSIDE Investigations Into The
UNIVERSITY OF CALIFORNIA RIVERSIDE Investigations into the Role of TAF1-mediated Phosphorylation in Gene Regulation A Dissertation submitted in partial satisfaction of the requirements for the degree of Doctor of Philosophy in Cell, Molecular and Developmental Biology by Brian James Gadd December 2012 Dissertation Committee: Dr. Xuan Liu, Chairperson Dr. Frank Sauer Dr. Frances M. Sladek Copyright by Brian James Gadd 2012 The Dissertation of Brian James Gadd is approved Committee Chairperson University of California, Riverside Acknowledgments I am thankful to Dr. Liu for her patience and support over the last eight years. I am deeply indebted to my committee members, Dr. Frank Sauer and Dr. Frances Sladek for the insightful comments on my research and this dissertation. Thanks goes out to CMDB, especially Dr. Bachant, Dr. Springer and Kathy Redd for their support. Thanks to all the members of the Liu lab both past and present. A very special thanks to the members of the Sauer lab, including Silvia, Stephane, David, Matt, Stephen, Ninuo, Toby, Josh, Alice, Alex and Flora. You have made all the years here fly by and made them so enjoyable. From the Sladek lab I want to thank Eugene, John, Linh and Karthi. Special thanks go out to all the friends I’ve made over the years here. Chris, Amber, Stephane and David, thank you so much for feeding me, encouraging me and keeping me sane. Thanks to the brothers for all your encouragement and prayers. To any I haven’t mentioned by name, I promise I haven’t forgotten all you’ve done for me during my graduate years. -
A Role for the Nlr Family Members Nlrc4 and Nlrp3 in Astrocytic Inflammasome Activation and Astrogliosis
A ROLE FOR THE NLR FAMILY MEMBERS NLRC4 AND NLRP3 IN ASTROCYTIC INFLAMMASOME ACTIVATION AND ASTROGLIOSIS Leslie C. Freeman A dissertation submitted to the faculty of the University of North Carolina at Chapel Hill in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Curriculum of Genetics and Molecular Biology. Chapel Hill 2016 Approved by: Jenny P. Y. Ting Glenn K. Matsushima Beverly H. Koller Silva S. Markovic-Plese Pauline. Kay Lund ©2016 Leslie C. Freeman ALL RIGHTS RESERVED ii ABSTRACT Leslie C. Freeman: A Role for the NLR Family Members NLRC4 and NLRP3 in Astrocytic Inflammasome Activation and Astrogliosis (Under the direction of Jenny P.Y. Ting) The inflammasome is implicated in many inflammatory diseases but has been primarily studied in the macrophage-myeloid lineage. Here we demonstrate a physiologic role for nucleotide-binding domain, leucine-rich repeat, CARD domain containing 4 (NLRC4) in brain astrocytes. NLRC4 has been primarily studied in the context of gram-negative bacteria, where it is required for the maturation of pro-caspase-1 to active caspase-1. We show the heightened expression of NLRC4 protein in astrocytes in a cuprizone model of neuroinflammation and demyelination as well as human multiple sclerotic brains. Similar to macrophages, NLRC4 in astrocytes is required for inflammasome activation by its known agonist, flagellin. However, NLRC4 in astrocytes also mediate inflammasome activation in response to lysophosphatidylcholine (LPC), an inflammatory molecule associated with neurologic disorders. In addition to NLRC4, astrocytic NLRP3 is required for inflammasome activation by LPC. Two biochemical assays show the interaction of NLRC4 with NLRP3, suggesting the possibility of a NLRC4-NLRP3 co-inflammasome. -
The RFX Complex Is Crucial for the Constitutive and CIITA-Mediated Transactivation of MHC Class I and 2-Microglobulin Genes
View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Immunity, Vol. 9, 531±541, October, 1998, Copyright 1998 by Cell Press The RFX Complex Is Crucial for the Constitutive and CIITA-Mediated Transactivation of MHC Class I and b2-Microglobulin Genes Sam J. P. Gobin,² Ad Peijnenburg,² of the NF-kB/Rel family and are thought to be essential Marja van Eggermond, Marlijn van Zutphen, for both constitutive and cytokine-induced expression Rian van den Berg, and Peter J. van den Elsen* (Girdlestone et al., 1993; Mansky et al., 1994). The ISRE Department of Immunohematology and Blood Bank is bound by factors of the interferon regulatory factor Leiden University Medical Center (IRF) family and mediates the induction of MHC class I 2333 ZA Leiden expression by interferons (Girdlestone et al., 1993). Site The Netherlands a was originally described as being important for the constitutive expression of MHC class I genes (Dey et al., 1992). However, a crucial role in a novel route of Summary HLA class I gene activation mediated by the class II transactivator (CIITA) has recently been attributed to In type III bare lymphocyte syndrome (BLS) patients, site a (Gobin et al., 1997; Martin et al., 1997). Enhancer defects in the RFX protein complex result in a lack of B contains an inverted CCAAT box sequence that plays MHC class II and reduced MHC class I cell surface a role in basal MHC class I gene transcription (Schoneich et al., 1997). In the promoter region of the m gene, expression. -
Genomic Analyses of PMBL Reveal New Drivers and Mechanisms of Sensitivity to PD-1 Blockade
Regular Article LYMPHOID NEOPLASIA Genomic analyses of PMBL reveal new drivers and mechanisms of sensitivity to PD-1 blockade Bjoern Chapuy,1,2,* Chip Stewart,3,* Andrew J. Dunford,3,* Jaegil Kim,3 Kirsty Wienand,1 Atanas Kamburov,3 Gabriel K. Griffin,4 Pei-Hsuan Chen,4 Ana Lako,4 Robert A. Redd,5 Claire M. Cote,1 Matthew D. Ducar,6 Aaron R. Thorner,6 Scott J. Rodig,4 Gad Getz,3,7,8,† Downloaded from https://ashpublications.org/blood/article-pdf/134/26/2369/1549702/bloodbld2019002067.pdf by Margaret Shipp on 30 December 2019 and Margaret A. Shipp1,† 1Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; 2Department of Hematology and Oncology, University Medical Center Gottingen,¨ Gottingen,¨ Germany; 3Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA; 4Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; 5Department of Data Sciences and 6Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, MA; and 7Department of Pathology and 8Center for Cancer Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA KEY POINTS Primary mediastinal large B-cell lymphomas (PMBLs) are aggressive tumors that typically present as large mediastinal masses in young women. PMBLs share clinical, transcriptional, l Comprehensive genomic analyses of and molecular features with classical Hodgkin lymphoma (cHL), including constitutive PMBL reveal new activation of nuclear factor kB (NF-kB), JAK/STAT signaling, and programmed cell death genetic drivers such protein 1 (PD-1)–mediated immune evasion. The demonstrated efficacy of PD-1 blockade in as ZNF217. relapsed/refractory PMBLs led to recent approval by the US Food and Drug Administration l High mutational and underscored the importance of characterizing targetable genetic vulnerabilities in this burden, MSI, and disease.