News archives


OCTOBER - DECEMBER 17

JULY - SEPTEMBER 17

APRIL - JUNE 17

JANUARY - MARCH 17

OCTOBER - DECEMBER 16

JULY - SEPTEMBER 16

APRIL - JUNE 16

JANUARY - MARCH 16

OCTOBER - DECEMBER 15

JULY - SEPTEMBER 15

APRIL - JUNE 15

JANUARY - MARCH 15

OCTOBER - DECEMBER 14

JULY - SEPTEMBER 14

APRIL - JUNE 14

JANUARY - MARCH 14

OCTOBER - DECEMBER 13

JULY - SEPTEMBER 13

APRIL - JUNE 13

JANUARY - MARCH 13

OCTOBER - DECEMBER 12

JULY - SEPTEMBER 12

APRIL - JUNE 12

JANUARY - MARCH 12

OCTOBER - DECEMBER 11

JULY - SEPTEMBER 11

APRIL - JUNE 11

JANUARY - MARCH 11

OCTOBER - DECEMBER 10

JULY - SEPTEMBER 10

APRIL - JUNE 10

JANUARY - MARCH 10

OCTOBER - DECEMBER 09

JULY - SEPTEMBER 09

APRIL - JUNE 09

JANUARY - MARCH 09

OCTOBER - DECEMBER 08

JULY - SEPTEMBER 08

APRIL - JUNE 08

JANUARY - MARCH 08

OCTOBER - DECEMBER 07

JULY - SEPTEMBER 07

APRIL - JUNE 07

JANUARY - MARCH 07

 
  current news   Press   selected story    
     
  14 September 2015  
 
Systematic Identification of Factors for Provirus Silencing in Embryonic Stem Cells
 
 




Authors
Bin Xia Yang1,22, Chadi A. EL Farran1,2,22, Hong Chao Guo3,22, Tao Yu1,2,22, Hai Tong Fang1, Hao Fei Wang1,2, Sharon Schlesinger4,5, Yu Fen Samantha Seah1, Germaine Yen Lin Goh6, Suat Peng Neo7, Yinghui Li9, Matthew C. Lorincz10, Vinay Tergaonkar9,21, Tit-Meng Lim2, Lingyi Chen3, Jayantha Gunaratne7,8, James J. Collins11,12,13,14, Stephen P. Goff4,5,15, George Q. Daley14,16,17,18,19, Hu Li20, Frederic A. Bard6,21, Yuin-Han Loh1,2,*

1 Epigenetics and Cell Fates Laboratory, A*STAR Institute of Molecular and Cell
  Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore
2 Department of Biological Sciences, National University of Singapore, 117543, Singapore
3 College of Life Sciences, Nankai University, Tianjin 300071, China
4 Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA
5 Department of Microbiology and Immunology, Columbia University, New York, NY 10032, US
6 Membrane Traffic Laboratory, A*STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive   Proteos, Singapore 138673, Singapore
7 Quantitative Proteomics Group, A*STAR Institute of Molecular and Cell Biology, 61 Biopolis Drive   Proteos, Singapore 138673, Singapore
8 Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore   117597, Singapore
9 Division of Cancer Genetics and Therapeutics, Laboratory of NF-κB Signaling, A*STAR Institute of   Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673, Singapore
10 Department of Medical Genetics, Life Sciences Institute, University of British Columbia, Vancouver,     British Columbia V6T 1Z3, Canada
11 Institute for Medical Engineering and Science Department of Biological Engineering, and Synthetic     Biology Center, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
12 Harvard-MIT Program in Health Sciences and Technology, Broad Institute of MIT and Harvard,     Cambridge, MA 02139, USA
13 Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA
14 Howard Hughes Medical Institute, Boston, MA 02115, USA
15 Howard Hughes Medical Institute, New York, NY 10032, USA
16 Stem Cell Transplantation Program, Division of Pediatric Hematology/Oncology, Boston Children’s     Hospital and Dana-Farber Cancer Institute, Boston, MA 02115, USA
17 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA     02115, USA
18 Harvard Stem Cell Institute, Boston, MA 02115, USA
19 Manton Center for Orphan Disease Research, Boston, MA 02115, USA
20 Center for Individualized Medicine, Department of Molecular Pharmacology & Experimental     Therapeutics, Mayo Clinic, Rochester, MN 55905, USA
21 Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore,     Singapore 119077, Singapore
22 These authors contributed equally to this work

*Correspondence: Yuin-Han Loh, Epigenetics and Cell Fates Laboratory, A*STAR
Institute of Molecular and Cell Biology, 61 Biopolis Drive Proteos, Singapore 138673,
Singapore; e-mail: yhloh@imcb.a-star.edu.sg

Published online in CELL on 10 September 2015

Please click here to see press release from A*STAR.

Abstract
Embryonic stem cells (ESCs) repress the expression of exogenous proviruses and endogenous retroviruses (ERVs). Here, we systematically dissected the cellular factors involved in provirus repression in embryonic carcinomas (ECs) and ESCs by a genome-wide siRNA screen. Histone chaperones (Chaf1a/b), sumoylation factors (Sumo2/Ube2i/Sae1/Uba2/Senp6) and chromatin modifiers (Trim28/Eset/Atf7ip) are key determinants that establish provirus silencing. RNA-seq analysis uncovered the roles of Chaf1a/b and sumoylation modifiers in the repression of ERVs. ChIP-seq analysis demonstrates direct recruitment of Chaf1a and Sumo2 to ERVs. Chaf1a reinforces transcriptional repression via its interaction with members of the NuRD complex (Kdm1a, Hdac1/2) and Eset, while Sumo2 orchestrates the provirus repressive function of the canonical Zfp809/Trim28/Eset machinery by sumoylation of Trim28. Our study reports a genome-wide atlas of functional nodes that mediate proviral silencing in ESCs, and illuminates the comprehensive, interconnected and multi-layered genetic and epigenetic mechanisms by which ESCs repress retroviruses within the genome.

Figure:

Figure legend: Virus silencing - Yang et al Graphical abstract


For more information on Jonathan Yuin-Han LOH ’s laboratory, please click here.