Roles of the CSE1L-Mediated Nuclear Import Pathway in Epigenetic
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Supplemental Materials ZNF281 Enhances Cardiac Reprogramming
Supplemental Materials ZNF281 enhances cardiac reprogramming by modulating cardiac and inflammatory gene expression Huanyu Zhou, Maria Gabriela Morales, Hisayuki Hashimoto, Matthew E. Dickson, Kunhua Song, Wenduo Ye, Min S. Kim, Hanspeter Niederstrasser, Zhaoning Wang, Beibei Chen, Bruce A. Posner, Rhonda Bassel-Duby and Eric N. Olson Supplemental Table 1; related to Figure 1. Supplemental Table 2; related to Figure 1. Supplemental Table 3; related to the “quantitative mRNA measurement” in Materials and Methods section. Supplemental Table 4; related to the “ChIP-seq, gene ontology and pathway analysis” and “RNA-seq” and gene ontology analysis” in Materials and Methods section. Supplemental Figure S1; related to Figure 1. Supplemental Figure S2; related to Figure 2. Supplemental Figure S3; related to Figure 3. Supplemental Figure S4; related to Figure 4. Supplemental Figure S5; related to Figure 6. Supplemental Table S1. Genes included in human retroviral ORF cDNA library. Gene Gene Gene Gene Gene Gene Gene Gene Symbol Symbol Symbol Symbol Symbol Symbol Symbol Symbol AATF BMP8A CEBPE CTNNB1 ESR2 GDF3 HOXA5 IL17D ADIPOQ BRPF1 CEBPG CUX1 ESRRA GDF6 HOXA6 IL17F ADNP BRPF3 CERS1 CX3CL1 ETS1 GIN1 HOXA7 IL18 AEBP1 BUD31 CERS2 CXCL10 ETS2 GLIS3 HOXB1 IL19 AFF4 C17ORF77 CERS4 CXCL11 ETV3 GMEB1 HOXB13 IL1A AHR C1QTNF4 CFL2 CXCL12 ETV7 GPBP1 HOXB5 IL1B AIMP1 C21ORF66 CHIA CXCL13 FAM3B GPER HOXB6 IL1F3 ALS2CR8 CBFA2T2 CIR1 CXCL14 FAM3D GPI HOXB7 IL1F5 ALX1 CBFA2T3 CITED1 CXCL16 FASLG GREM1 HOXB9 IL1F6 ARGFX CBFB CITED2 CXCL3 FBLN1 GREM2 HOXC4 IL1F7 -
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. -
In Vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in 2 COVID-19 3
bioRxiv preprint doi: https://doi.org/10.1101/2020.12.29.424728; this version posted December 30, 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 In vitro Targeting of Transcription Factors to Control the Cytokine Release Syndrome in 2 COVID-19 3 4 Clarissa S. Santoso1, Zhaorong Li2, Jaice T. Rottenberg1, Xing Liu1, Vivian X. Shen1, Juan I. 5 Fuxman Bass1,2 6 7 1Department of Biology, Boston University, Boston, MA 02215, USA; 2Bioinformatics Program, 8 Boston University, Boston, MA 02215, USA 9 10 Corresponding author: 11 Juan I. Fuxman Bass 12 Boston University 13 5 Cummington Mall 14 Boston, MA 02215 15 Email: [email protected] 16 Phone: 617-353-2448 17 18 Classification: Biological Sciences 19 20 Keywords: COVID-19, cytokine release syndrome, cytokine storm, drug repurposing, 21 transcriptional regulators 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.12.29.424728; this version posted December 30, 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. 22 Abstract 23 Treatment of the cytokine release syndrome (CRS) has become an important part of rescuing 24 hospitalized COVID-19 patients. Here, we systematically explored the transcriptional regulators 25 of inflammatory cytokines involved in the COVID-19 CRS to identify candidate transcription 26 factors (TFs) for therapeutic targeting using approved drugs. -
Pathobiology of Paget's Disease of Bone
J Bone Metab 2014;21:85-98 http://dx.doi.org/10.11005/jbm.2014.21.2.85 pISSN 2287-6375 eISSN 2287-7029 Review Article Pathobiology of Paget’s Disease of Bone Deborah L. Galson1, G. David Roodman2,3 1Department of Medicine/Hematology-Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh PA; 2Department of Medicine/Hematology-Oncology, Indiana University, Indianapolis IN; 3Veterans Administration Medical Center, Indianapolis, IN, USA. Corresponding author G. David Roodman Paget’s disease of bone is characterized by highly localized areas of increased Department of Medicine, Hematology bone resorption accompanied by exuberant, but aberrant new bone formation Oncology, School of Medicine, Indiana with the primary cellular abnormality in osteoclasts. Paget’s disease provides an University, 980 West Walnut Street, R3, important paradigm for understanding the molecular mechanisms regulating Indianapolis, IN 46202, USA both osteoclast formation and osteoclast-induced osteoblast activity. Both genet- Tel: +317-278-6255 Fax: +317-274-0396 ic and environmental etiologies have been implicated in Paget’s disease, but their E-mail: [email protected] relative contributions are just beginning to be defined. To date, the only gene with mutations in the coding region linked to Paget’s disease is sequestosome-1 Received: February 15, 2014 (SQSTM1), which encodes the p62 protein, and these mutations lead to elevated Revised: April 2, 2014 Accepted: April 2, 2014 cytokine activation of NF-B in osteoclasts but do not induce a “pagetic osteoclast” phenotype. Further, genetic mutations linked to Paget’s appear insufficient to No potential conflict of interest relevant to this cause Paget’s disease and additional susceptibility loci or environmental factors article was reported. -
Downregulation of Carnitine Acyl-Carnitine Translocase by Mirnas
Page 1 of 288 Diabetes 1 Downregulation of Carnitine acyl-carnitine translocase by miRNAs 132 and 212 amplifies glucose-stimulated insulin secretion Mufaddal S. Soni1, Mary E. Rabaglia1, Sushant Bhatnagar1, Jin Shang2, Olga Ilkayeva3, Randall Mynatt4, Yun-Ping Zhou2, Eric E. Schadt6, Nancy A.Thornberry2, Deborah M. Muoio5, Mark P. Keller1 and Alan D. Attie1 From the 1Department of Biochemistry, University of Wisconsin, Madison, Wisconsin; 2Department of Metabolic Disorders-Diabetes, Merck Research Laboratories, Rahway, New Jersey; 3Sarah W. Stedman Nutrition and Metabolism Center, Duke Institute of Molecular Physiology, 5Departments of Medicine and Pharmacology and Cancer Biology, Durham, North Carolina. 4Pennington Biomedical Research Center, Louisiana State University system, Baton Rouge, Louisiana; 6Institute for Genomics and Multiscale Biology, Mount Sinai School of Medicine, New York, New York. Corresponding author Alan D. Attie, 543A Biochemistry Addition, 433 Babcock Drive, Department of Biochemistry, University of Wisconsin-Madison, Madison, Wisconsin, (608) 262-1372 (Ph), (608) 263-9608 (fax), [email protected]. Running Title: Fatty acyl-carnitines enhance insulin secretion Abstract word count: 163 Main text Word count: 3960 Number of tables: 0 Number of figures: 5 Diabetes Publish Ahead of Print, published online June 26, 2014 Diabetes Page 2 of 288 2 ABSTRACT We previously demonstrated that micro-RNAs 132 and 212 are differentially upregulated in response to obesity in two mouse strains that differ in their susceptibility to obesity-induced diabetes. Here we show the overexpression of micro-RNAs 132 and 212 enhances insulin secretion (IS) in response to glucose and other secretagogues including non-fuel stimuli. We determined that carnitine acyl-carnitine translocase (CACT, Slc25a20) is a direct target of these miRNAs. -
SF3B1-Mutated Chronic Lymphocytic Leukemia Shows Evidence Of
SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation by Federico Pozzo, Tamara Bittolo, Erika Tissino, Filippo Vit, Elena Vendramini, Luca Laurenti, Giovanni D'Arena, Jacopo Olivieri, Gabriele Pozzato, Francesco Zaja, Annalisa Chiarenza, Francesco Di Raimondo, Antonella Zucchetto, Riccardo Bomben, Francesca Maria Rossi, Giovanni Del Poeta, Michele Dal Bo, and Valter Gattei Haematologica 2020 [Epub ahead of print] Citation: Federico Pozzo, Tamara Bittolo, Erika Tissino, Filippo Vit, Elena Vendramini, Luca Laurenti, Giovanni D'Arena, Jacopo Olivieri, Gabriele Pozzato, Francesco Zaja, Annalisa Chiarenza, Francesco Di Raimondo, Antonella Zucchetto, Riccardo Bomben, Francesca Maria Rossi, Giovanni Del Poeta, Michele Dal Bo, and Valter Gattei SF3B1-mutated chronic lymphocytic leukemia shows evidence of NOTCH1 pathway activation including CD20 downregulation. Haematologica. 2020; 105:xxx doi:10.3324/haematol.2020.261891 Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that have completed a regular peer review and have been accepted for publication. E-publishing of this PDF file has been approved by the authors. After having E-published Ahead of Print, manuscripts will then undergo technical and English editing, typesetting, proof correction and be presented for the authors' final approval; the final version of the manuscript will -
Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors
University of Cincinnati Date: 12/20/2010 I, Arturo R Maldonado , hereby submit this original work as part of the requirements for the degree of Doctor of Philosophy in Developmental Biology. It is entitled: Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors Student's name: Arturo R Maldonado This work and its defense approved by: Committee chair: Jeffrey Whitsett Committee member: Timothy Crombleholme, MD Committee member: Dan Wiginton, PhD Committee member: Rhonda Cardin, PhD Committee member: Tim Cripe 1297 Last Printed:1/11/2011 Document Of Defense Form Molecular Targeting and Enhancing Anticancer Efficacy of Oncolytic HSV-1 to Midkine Expressing Tumors A dissertation submitted to the Graduate School of the University of Cincinnati College of Medicine in partial fulfillment of the requirements for the degree of DOCTORATE OF PHILOSOPHY (PH.D.) in the Division of Molecular & Developmental Biology 2010 By Arturo Rafael Maldonado B.A., University of Miami, Coral Gables, Florida June 1993 M.D., New Jersey Medical School, Newark, New Jersey June 1999 Committee Chair: Jeffrey A. Whitsett, M.D. Advisor: Timothy M. Crombleholme, M.D. Timothy P. Cripe, M.D. Ph.D. Dan Wiginton, Ph.D. Rhonda D. Cardin, Ph.D. ABSTRACT Since 1999, cancer has surpassed heart disease as the number one cause of death in the US for people under the age of 85. Malignant Peripheral Nerve Sheath Tumor (MPNST), a common malignancy in patients with Neurofibromatosis, and colorectal cancer are midkine- producing tumors with high mortality rates. In vitro and preclinical xenograft models of MPNST were utilized in this dissertation to study the role of midkine (MDK), a tumor-specific gene over- expressed in these tumors and to test the efficacy of a MDK-transcriptionally targeted oncolytic HSV-1 (oHSV). -
(12) Patent Application Publication (10) Pub. No.: US 2009/0269772 A1 Califano Et Al
US 20090269772A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0269772 A1 Califano et al. (43) Pub. Date: Oct. 29, 2009 (54) SYSTEMS AND METHODS FOR Publication Classification IDENTIFYING COMBINATIONS OF (51) Int. Cl. COMPOUNDS OF THERAPEUTIC INTEREST CI2O I/68 (2006.01) CI2O 1/02 (2006.01) (76) Inventors: Andrea Califano, New York, NY G06N 5/02 (2006.01) (US); Riccardo Dalla-Favera, New (52) U.S. Cl. ........... 435/6: 435/29: 706/54; 707/E17.014 York, NY (US); Owen A. (57) ABSTRACT O'Connor, New York, NY (US) Systems, methods, and apparatus for searching for a combi nation of compounds of therapeutic interest are provided. Correspondence Address: Cell-based assays are performed, each cell-based assay JONES DAY exposing a different sample of cells to a different compound 222 EAST 41ST ST in a plurality of compounds. From the cell-based assays, a NEW YORK, NY 10017 (US) Subset of the tested compounds is selected. For each respec tive compound in the Subset, a molecular abundance profile from cells exposed to the respective compound is measured. (21) Appl. No.: 12/432,579 Targets of transcription factors and post-translational modu lators of transcription factor activity are inferred from the (22) Filed: Apr. 29, 2009 molecular abundance profile data using information theoretic measures. This data is used to construct an interaction net Related U.S. Application Data work. Variances in edges in the interaction network are used to determine the drug activity profile of compounds in the (60) Provisional application No. 61/048.875, filed on Apr. -
The Hormone-Bound Vitamin D Receptor Regulates Turnover of Target
The hormone-bound vitamin D receptor regulates turnover of target proteins of the SCFFBW7 E3 ligase By Reyhaneh Salehi Tabar Department of Experimental Medicine McGill University Montreal, QC, Canada April 2016 A thesis submitted to McGill University in partial fulfillment of the requirements of the degree of Doctor of Philosophy © Reyhaneh Salehi Tabar 1 Table of Contents Abbreviations ................................................................................................................................................ 7 Abstract ....................................................................................................................................................... 10 Rèsumè ....................................................................................................................................................... 13 Acknowledgements ..................................................................................................................................... 16 Preface ........................................................................................................................................................ 17 Contribution of authors .............................................................................................................................. 18 Chapter 1-Literature review........................................................................................................................ 20 1.1. General introduction and overview of thesis ............................................................................ -
Proteomic Profiling and Genome-Wide Mapping of O-Glcnac Chromatin
ARTICLE https://doi.org/10.1038/s41467-020-19579-y OPEN Proteomic profiling and genome-wide mapping of O-GlcNAc chromatin-associated proteins reveal an O-GlcNAc-regulated genotoxic stress response Yubo Liu 1,3, Qiushi Chen 2,3, Nana Zhang1, Keren Zhang2, Tongyi Dou1, Yu Cao1, Yimin Liu1, Kun Li1, ✉ ✉ Xinya Hao1, Xueqin Xie1, Wenli Li1, Yan Ren 2 & Jianing Zhang 1 fi 1234567890():,; O-GlcNAc modi cation plays critical roles in regulating the stress response program and cellular homeostasis. However, systematic and multi-omics studies on the O-GlcNAc regu- lated mechanism have been limited. Here, comprehensive data are obtained by a chemical reporter-based method to survey O-GlcNAc function in human breast cancer cells stimulated with the genotoxic agent adriamycin. We identify 875 genotoxic stress-induced O-GlcNAc chromatin-associated proteins (OCPs), including 88 O-GlcNAc chromatin-associated tran- scription factors and cofactors (OCTFs), subsequently map their genomic loci, and construct a comprehensive transcriptional reprogramming network. Notably, genotoxicity-induced O- GlcNAc enhances the genome-wide interactions of OCPs with chromatin. The dynamic binding switch of hundreds of OCPs from enhancers to promoters is identified as a crucial feature in the specific transcriptional activation of genes involved in the adaptation of cancer cells to genotoxic stress. The OCTF nuclear factor erythroid 2-related factor-1 (NRF1) is found to be a key response regulator in O-GlcNAc-modulated cellular homeostasis. These results provide a valuable clue suggesting that OCPs act as stress sensors by regulating the expression of various genes to protect cancer cells from genotoxic stress. -
US 2021/0108193 A1 Mali Et Al
US 20210108193A1IN IN ( 19 ) United States ( 12 ) Patent Application Publication ( 10 ) Pub . No .: US 2021/0108193 A1 Mali et al . ( 43 ) Pub . Date : Apr. 15 , 2021 ( 54 ) METHODS FOR SCREENING GENETIC ( 52 ) U.S. CI . PERTURBATIONS CPC C12N 15/1065 ( 2013.01 ) ; C12N 5/069 ( 2013.01 ) ; C12N 15/86 ( 2013.01 ); CI2N ( 71 ) Applicant: The Regents of the University of 2740/15052 ( 2013.01) ; C12N 2506/45 ( 2013.01 ) ; C12N 2740/15043 ( 2013.01 ); A61K California , Oakland , CA ( US ) 35/44 ( 2013.01 ) ( 72 ) Inventors: Prashant Mali , La Jolla , CA (US ) ; ( 57 ) ABSTRACT Udit Parekh , La Jolla , CA (US ); Yan Understanding the complex effects of genetic perturbations Wu , La Jolla , CA (US ); Kun Zhang , on cellular state and fitness in human pluripotent stem cells La Jolla , CA ( US ) ( hPSCs) has been challenging using traditional pooled screening techniques which typically rely on unidimensional phenotypic readouts . Here , Applicants use barcoded open reading frame (ORF ) overexpression libraries with a ( 21 ) Appl. No .: 17 / 028,836 coupled single - cell RNA sequencing ( scRNA - seq ) and fit ness screening approach , a technique we call SEUSS ( Scal ( 22 ) Filed : Sep. 22 , 2020 comprehensiveable fUnctional assaying Screening platform by Sequencing . Using this) , systemto establish , Appli a cants perturbed hPSCs with a library of developmentally critical transcription factors ( TFs ), and assayed the impact of Related U.S. Application Data TF overexpression on fitness and transcriptomic cell state across multiple media conditions. Applicants further lever ( 60 ) Provisional application No. 62 / 904,614 , filed on Sep. aged the versatility of the ORF library approach to system 23 , 2019 . atically assay mutant gene libraries and also whole gene families. -
Dynamic Regulation of Chromatin Accessibility by Pluripotency Transcription Factors
bioRxiv preprint doi: https://doi.org/10.1101/698571; this version posted July 11, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Dynamic regulation of chromatin accessibility by pluripotency transcription factors 2 across the cell cycle 3 4 Elias T. Friman1, Cédric Deluz1, Antonio C.A. Meireles-Filho1, Subashika Govindan1, 5 Vincent Gardeux1, Bart Deplancke1, David M. Suter1 6 7 Corresponding author: [email protected] 8 9 Affiliations 10 1Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de 11 Lausanne (EPFL), CH-1015 Lausanne, Switzerland 12 13 Abstract 14 The pioneer activity of transcription factors allows for opening of inaccessible regulatory 15 elements and has been extensively studied in the context of cellular differentiation and 16 reprogramming. In contrast, the function of pioneer activity in self-renewing cell divisions 17 and across the cell cycle is poorly understood. Here we assessed the interplay between 18 OCT4 and SOX2 in controlling chromatin accessibility of mouse embryonic stem cells. We 19 found that OCT4 and SOX2 operate in a largely independent manner even at co-occupied 20 sites, and that their cooperative binding is mostly mediated indirectly through regulation of 21 chromatin accessibility. Controlled protein degradation strategies revealed that the 22 uninterrupted presence of OCT4 is required for post-mitotic re-establishment and 23 interphase maintenance of chromatin accessibility, and that highly OCT4-bound enhancers 24 are particularly vulnerable to transient loss of OCT4 expression. Our study sheds light on 25 the constant pioneer activity required to maintain the dynamic pluripotency regulatory 26 landscape in an accessible state.