Supplementary Material Sumoylation Regulates the Chromatin
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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. -
Transcriptome Sequencing and Genome-Wide Association Analyses Reveal Lysosomal Function and Actin Cytoskeleton Remodeling in Schizophrenia and Bipolar Disorder
Molecular Psychiatry (2015) 20, 563–572 © 2015 Macmillan Publishers Limited All rights reserved 1359-4184/15 www.nature.com/mp ORIGINAL ARTICLE Transcriptome sequencing and genome-wide association analyses reveal lysosomal function and actin cytoskeleton remodeling in schizophrenia and bipolar disorder Z Zhao1,6,JXu2,6, J Chen3,6, S Kim4, M Reimers3, S-A Bacanu3,HYu1, C Liu5, J Sun1, Q Wang1, P Jia1,FXu2, Y Zhang2, KS Kendler3, Z Peng2 and X Chen3 Schizophrenia (SCZ) and bipolar disorder (BPD) are severe mental disorders with high heritability. Clinicians have long noticed the similarities of clinic symptoms between these disorders. In recent years, accumulating evidence indicates some shared genetic liabilities. However, what is shared remains elusive. In this study, we conducted whole transcriptome analysis of post-mortem brain tissues (cingulate cortex) from SCZ, BPD and control subjects, and identified differentially expressed genes in these disorders. We found 105 and 153 genes differentially expressed in SCZ and BPD, respectively. By comparing the t-test scores, we found that many of the genes differentially expressed in SCZ and BPD are concordant in their expression level (q ⩽ 0.01, 53 genes; q ⩽ 0.05, 213 genes; q ⩽ 0.1, 885 genes). Using genome-wide association data from the Psychiatric Genomics Consortium, we found that these differentially and concordantly expressed genes were enriched in association signals for both SCZ (Po10 − 7) and BPD (P = 0.029). To our knowledge, this is the first time that a substantially large number of genes show concordant expression and association for both SCZ and BPD. Pathway analyses of these genes indicated that they are involved in the lysosome, Fc gamma receptor-mediated phagocytosis, regulation of actin cytoskeleton pathways, along with several cancer pathways. -
Genome-Wide DNA Methylation Analysis of KRAS Mutant Cell Lines Ben Yi Tew1,5, Joel K
www.nature.com/scientificreports OPEN Genome-wide DNA methylation analysis of KRAS mutant cell lines Ben Yi Tew1,5, Joel K. Durand2,5, Kirsten L. Bryant2, Tikvah K. Hayes2, Sen Peng3, Nhan L. Tran4, Gerald C. Gooden1, David N. Buckley1, Channing J. Der2, Albert S. Baldwin2 ✉ & Bodour Salhia1 ✉ Oncogenic RAS mutations are associated with DNA methylation changes that alter gene expression to drive cancer. Recent studies suggest that DNA methylation changes may be stochastic in nature, while other groups propose distinct signaling pathways responsible for aberrant methylation. Better understanding of DNA methylation events associated with oncogenic KRAS expression could enhance therapeutic approaches. Here we analyzed the basal CpG methylation of 11 KRAS-mutant and dependent pancreatic cancer cell lines and observed strikingly similar methylation patterns. KRAS knockdown resulted in unique methylation changes with limited overlap between each cell line. In KRAS-mutant Pa16C pancreatic cancer cells, while KRAS knockdown resulted in over 8,000 diferentially methylated (DM) CpGs, treatment with the ERK1/2-selective inhibitor SCH772984 showed less than 40 DM CpGs, suggesting that ERK is not a broadly active driver of KRAS-associated DNA methylation. KRAS G12V overexpression in an isogenic lung model reveals >50,600 DM CpGs compared to non-transformed controls. In lung and pancreatic cells, gene ontology analyses of DM promoters show an enrichment for genes involved in diferentiation and development. Taken all together, KRAS-mediated DNA methylation are stochastic and independent of canonical downstream efector signaling. These epigenetically altered genes associated with KRAS expression could represent potential therapeutic targets in KRAS-driven cancer. Activating KRAS mutations can be found in nearly 25 percent of all cancers1. -
Accompanies CD8 T Cell Effector Function Global DNA Methylation
Global DNA Methylation Remodeling Accompanies CD8 T Cell Effector Function Christopher D. Scharer, Benjamin G. Barwick, Benjamin A. Youngblood, Rafi Ahmed and Jeremy M. Boss This information is current as of October 1, 2021. J Immunol 2013; 191:3419-3429; Prepublished online 16 August 2013; doi: 10.4049/jimmunol.1301395 http://www.jimmunol.org/content/191/6/3419 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2013/08/20/jimmunol.130139 Material 5.DC1 References This article cites 81 articles, 25 of which you can access for free at: http://www.jimmunol.org/content/191/6/3419.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on October 1, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Global DNA Methylation Remodeling Accompanies CD8 T Cell Effector Function Christopher D. Scharer,* Benjamin G. Barwick,* Benjamin A. Youngblood,*,† Rafi Ahmed,*,† and Jeremy M. -
CARBOPLATIN and PACLITAXEL a Dissertation SUBMITTED
PHARMACOGENOMICS OF CHEMOTHERAPEUTIC AGENTS: CARBOPLATIN AND PACLITAXEL A Dissertation SUBMITTED TO THE FACULTY OF UNIVERSITY OF MINNESOTA BY Taraswi Mitra Ghosh IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY Dr. Jatinder K. Lamba May 2017 © Taraswi Mitra Ghosh, 2017 ACKNOWLEDGEMENTS At this special moment when I have reached the concluding stages of my Doctoral research and am ready to embark upon another voyage in my scientific career, I would like to take the opportunity to acknowledge the contributions of the people who have shaped up my life and career. First and foremost, I would like to thank Almighty God for giving me the strength to overcome all the challenges, for giving me the motivation to learn and to acquire knowledge. I would like to thank Dr. Jatinder Lamba, my adviser. I have learned a lot from her and am extremely thankful to her. She has helped me develop my scientific temper and inquisitive thinking. I would like to express my sincere gratitude towards my committee members. Dr. Mark Kirstein, my committee chair, has been a constant support. He has helped me develop my concepts in Pharmacokinetics. His insightful questions during our discussions have encouraged me to think deep and broaden my knowledge base. Dr. Angela Birnbaum, my committee member and DGS, has always been a strong support. Working with her was a very nice and cherishable experience for me. She has provided me the confidence to undertake independent projects- an experience which I am sure will be helpful in my future as a Scientist. I would like to thank Dr. -
Identification of Potential Key Genes and Pathway Linked with Sporadic Creutzfeldt-Jakob Disease Based on Integrated Bioinformatics Analyses
medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Identification of potential key genes and pathway linked with sporadic Creutzfeldt-Jakob disease based on integrated bioinformatics analyses 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 NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice. medRxiv preprint doi: https://doi.org/10.1101/2020.12.21.20248688; this version posted December 24, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Abstract Sporadic Creutzfeldt-Jakob disease (sCJD) is neurodegenerative disease also called prion disease linked with poor prognosis. The aim of the current study was to illuminate the underlying molecular mechanisms of sCJD. The mRNA microarray dataset GSE124571 was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened. -
Single Cell Regulatory Landscape of the Mouse Kidney Highlights Cellular Differentiation Programs and Disease Targets
ARTICLE https://doi.org/10.1038/s41467-021-22266-1 OPEN Single cell regulatory landscape of the mouse kidney highlights cellular differentiation programs and disease targets Zhen Miao 1,2,3,8, Michael S. Balzer 1,2,8, Ziyuan Ma 1,2,8, Hongbo Liu1,2, Junnan Wu 1,2, Rojesh Shrestha 1,2, Tamas Aranyi1,2, Amy Kwan4, Ayano Kondo 4, Marco Pontoglio 5, Junhyong Kim6, ✉ Mingyao Li 7, Klaus H. Kaestner2,4 & Katalin Susztak 1,2,4 1234567890():,; Determining the epigenetic program that generates unique cell types in the kidney is critical for understanding cell-type heterogeneity during tissue homeostasis and injury response. Here, we profile open chromatin and gene expression in developing and adult mouse kidneys at single cell resolution. We show critical reliance of gene expression on distal regulatory elements (enhancers). We reveal key cell type-specific transcription factors and major gene- regulatory circuits for kidney cells. Dynamic chromatin and expression changes during nephron progenitor differentiation demonstrates that podocyte commitment occurs early and is associated with sustained Foxl1 expression. Renal tubule cells follow a more complex differentiation, where Hfn4a is associated with proximal and Tfap2b with distal fate. Mapping single nucleotide variants associated with human kidney disease implicates critical cell types, developmental stages, genes, and regulatory mechanisms. The single cell multi-omics atlas reveals key chromatin remodeling events and gene expression dynamics associated with kidney development. 1 Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. 2 Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. -
Evidence for a Role of Developmental Genes in the Origin of Obesity and Body Fat Distribution
Evidence for a role of developmental genes in the origin of obesity and body fat distribution Stephane Gesta*, Matthias Blu¨ her†, Yuji Yamamoto*, Andrew W. Norris*, Janin Berndt†, Susan Kralisch†, Jeremie Boucher*, Choy Lewis*, and C. Ronald Kahn*‡ *Joslin Diabetes Center and Harvard Medical School, Boston, MA 02215; and †Department of Internal Medicine III, University of Leipzig, 04103 Leipzig, Germany Contributed by C. Ronald Kahn, March 9, 2006 Obesity, especially central obesity, is a hereditable trait associated In the present study, we have explored the hypothesis that with a high risk for development of diabetes and metabolic patterns of fat distribution and, perhaps, to some degree, obesity disorders. Combined gene expression analysis of adipocyte- and itself may have a developmental genetic origin. Indeed, we find preadipocyte-containing fractions from intraabdominal and sub- major differences in expression of multiple genes involved in cutaneous adipose tissue of mice revealed coordinated depot- embryonic development and pattern specification between adipo- specific differences in expression of multiple genes involved in cytes taken from intraabdominal and s.c. depots in rodents and embryonic development and pattern specification. These differ- humans. We also demonstrate similar differences in the stromo- ences were intrinsic and persisted during in vitro culture and vascular fraction (SVF)-containing preadipocytes and that these differentiation. Similar depot-specific differences in expression of differences persist in culture. Most importantly, we demonstrate developmental genes were observed in human subcutaneous ver- that some of these developmental genes exhibit changes in expres- sus visceral adipose tissue. Furthermore, in humans, several genes sion that are closely correlated with the level of obesity and the exhibited changes in expression that correlated closely with body pattern of fat distribution. -
Supplementary Figure Legends
1 Supplementary Figure legends 2 Supplementary Figure 1. 3 Experimental workflow. 4 5 Supplementary Figure 2. 6 IRF9 binding to promoters. 7 a) Verification of mIRF9 antibody by site-directed ChIP. IFNβ-stimulated binding of IRF9 to 8 the ISRE sequences of Mx2 was analyzed using BMDMs of WT and Irf9−/− (IRF9-/-) mice. 9 Cells were treated with 250 IU/ml of IFNβ for 1.5h. Data represent mean and SEM values of 10 three independent experiments. P-values were calculated using the paired ratio t-test (*P ≤ 11 0.05; **P ≤ 0.01, ***P ≤ 0.001). 12 b) Browser tracks showing complexes assigned as STAT-IRF9 in IFNγ treated wild type 13 BMDMs. Input, STAT2, IRF9 (scale 0-200). STAT1 (scale 0-150). 14 15 Supplementary Figure 3. 16 Experimental system for BioID. 17 a) Kinetics of STAT1, STAT2 and IRF9 synthesis in Raw 264.7 macrophages and wild type 18 BMDMs treated with 250 IU/ml as indicated. Whole-cell extracts were tested in western blot 19 for STAT1 phosphorylation at Y701 and of STAT2 at Y689 as well as total STAT1, STAT2, 20 IRF9 and GAPDH levels. The blots are representative of three independent experiments. b) 21 Irf9-/- mouse embryonic fibroblasts (MEFs) were transiently transfected with the indicated 22 expression vectors, including constitutively active IRF7-M15. One day after transfection, 23 RNA was isolated and Mx2 expression determined by qPCR. c) Myc-BirA*-IRF9 transgenic 24 Raw 264.7 were treated with increasing amounts of doxycycline (dox) (0,2µg/ml, 0,4µg/ml, 25 0,6µg/ml, 0,8µg/ml, 1mg/ml) and 50µM biotin. -
Microrna Modulate Alveolar Epithelial Response to Cyclic Stretch
University of Pennsylvania ScholarlyCommons Departmental Papers (BE) Department of Bioengineering 2012 MicroRNA Modulate Alveolar Epithelial Response to Cyclic Stretch Nadir Yehya University of Pennsylvania, [email protected] Adi Yerrapureddy University of Pennsylvania John Tobias University of Pennsylvania, [email protected] Susan S. Margulies University of Pennsylvania, [email protected] Follow this and additional works at: https://repository.upenn.edu/be_papers Part of the Biomedical Engineering and Bioengineering Commons Recommended Citation Yehya, N., Yerrapureddy, A., Tobias, J., & Margulies, S. S. (2012). MicroRNA Modulate Alveolar Epithelial Response to Cyclic Stretch. BMC Genomics, 13 (154), http://dx.doi.org/10.1186/1471-2164-13-154 This paper is posted at ScholarlyCommons. https://repository.upenn.edu/be_papers/205 For more information, please contact [email protected]. MicroRNA Modulate Alveolar Epithelial Response to Cyclic Stretch Abstract Background MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression implicated in multiple cellular processes. Cyclic stretch of alveoli is characteristic of mechanical ventilation, and is postulated to be partly responsible for the lung injury and inflammation in entilatv or-induced lung injury. We propose that miRNAs may regulate some of the stretch response, and therefore hypothesized that miRNAs would be differentially expressed between cyclically stretched and unstretched rat alveolar epithelial cells (RAECs). Results RAECs were isolated and cultured to express type I epithelial characteristics. They were then equibiaxially stretched to 25% change in surface area at 15 cycles/minute for 1 hour or 6 hours, or served as unstretched controls, and miRNAs were extracted. Expression profiling of the miRNAs with at least 1.5-fold change over controls revealed 42 miRNAs were regulated (34 up and 8 down) with stretch. -
Aberrant HOXC Expression Accompanies the Malignant Phenotype in Human Prostate1
[CANCER RESEARCH 63, 5879–5888, September 15, 2003] Aberrant HOXC Expression Accompanies the Malignant Phenotype in Human Prostate1 Gary J. Miller,2 Heidi L. Miller, Adrie van Bokhoven, James R. Lambert, Priya N. Werahera, Osvaldo Schirripa,3 M. Scott Lucia, and Steven K. Nordeen4 Department of Pathology, University of Colorado Health Sciences Center, Denver, Colorado 80262 ABSTRACT breast (13, 14), and renal (15) carcinomas; melanomas (16); and squamous carcinomas of the skin (17). Because the genes implicated Dysregulation of HOX gene expression has been implicated as a factor show little consensus, the dysregulation may be a tissue-specific in malignancies for a number of years. However, no consensus has perturbation of the existing HOX expression pattern rather than a emerged regarding specific causative genes. Using a degenerate reverse transcription-PCR technique, we show up-regulation of genes from the single causative gene. Tissue-specific expression patterns have been HOXC cluster in malignant prostate cell lines and lymph node metastases. reported in kidney and colon, by Northern blot analysis (12, 15). When relative expression levels of the four HOX clusters were examined, Primary tumors in both kidney and colon showed variations in spe- lymph node metastases and cell lines derived from lymph node metastases cific HOX gene expression from the corresponding normal tissue, but exhibited very similar patterns, patterns distinct from those in benign cells overall expression patterns for individual tumors were not reported. or malignant cell lines derived from other tumor sites. Specific reverse Only primary kidney tumors were examined (15), but liver metastases transcription-PCR for HOXC4, HOXC5, HOXC6, and HOXC8 confirmed from colon tumors reportedly displayed expression of specific HOX overexpression of these genes in malignant cell lines and lymph node genes similar to that seen in either primary colon tumors or normal metastases. -
Target Gene Gene Description Validation Diana Miranda
Supplemental Table S1. Mmu-miR-183-5p in silico predicted targets. TARGET GENE GENE DESCRIPTION VALIDATION DIANA MIRANDA MIRBRIDGE PICTAR PITA RNA22 TARGETSCAN TOTAL_HIT AP3M1 adaptor-related protein complex 3, mu 1 subunit V V V V V V V 7 BTG1 B-cell translocation gene 1, anti-proliferative V V V V V V V 7 CLCN3 chloride channel, voltage-sensitive 3 V V V V V V V 7 CTDSPL CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase-like V V V V V V V 7 DUSP10 dual specificity phosphatase 10 V V V V V V V 7 MAP3K4 mitogen-activated protein kinase kinase kinase 4 V V V V V V V 7 PDCD4 programmed cell death 4 (neoplastic transformation inhibitor) V V V V V V V 7 PPP2R5C protein phosphatase 2, regulatory subunit B', gamma V V V V V V V 7 PTPN4 protein tyrosine phosphatase, non-receptor type 4 (megakaryocyte) V V V V V V V 7 EZR ezrin V V V V V V 6 FOXO1 forkhead box O1 V V V V V V 6 ANKRD13C ankyrin repeat domain 13C V V V V V V 6 ARHGAP6 Rho GTPase activating protein 6 V V V V V V 6 BACH2 BTB and CNC homology 1, basic leucine zipper transcription factor 2 V V V V V V 6 BNIP3L BCL2/adenovirus E1B 19kDa interacting protein 3-like V V V V V V 6 BRMS1L breast cancer metastasis-suppressor 1-like V V V V V V 6 CDK5R1 cyclin-dependent kinase 5, regulatory subunit 1 (p35) V V V V V V 6 CTDSP1 CTD (carboxy-terminal domain, RNA polymerase II, polypeptide A) small phosphatase 1 V V V V V V 6 DCX doublecortin V V V V V V 6 ENAH enabled homolog (Drosophila) V V V V V V 6 EPHA4 EPH receptor A4 V V V V V V 6 FOXP1 forkhead box P1 V