title: Asynchronous transcriptional silencing of individual retroviral genomes in embryonic cells.
abstract: BACKGROUND
  Retroviral DNAs are profoundly silenced at the transcriptional level in embryonic cell types. The transcriptional profile of pluripotent stem cells has been demonstrated to be extremely heterogeneous from cell to cell, and how the silencing of retroviral DNAs is achieved is not yet well characterized.
  
  
  RESULTS
  In the current study, we investigated the transcriptional silencing dynamics in stem cells by independently monitoring the expression of two Moloney murine leukemia virus (MMLV) retroviral vectors newly introduced into embryonic carcinoma (EC) cells. Although MMLV is efficiently silenced by epigenetic mechanisms in most such cells, a small number of the doubly-transduced EC cells transiently show double-positive proviral expression. These cells were sorted and their expression patterns were studied over time as silencing is established.
  
  
  CONCLUSIONS
  Our data suggest that retroviral silencing occurs stochastically, in an individual locus-specific fashion, and often without synchronous silencing of both viruses in the same cells. Surprisingly, the chromatin modifications that mark the silenced proviruses are unchanged even in cells that temporarily escape silencing. This local silencing effect is a feature of stem cell epigenomic regulation that has not previously been revealed.
authors.forename: Sharon
authors.initials: S
authors.lastname: Schlesinger
authors.forename: Eran
authors.initials: E
authors.lastname: Meshorer
authors.affiliation: Department of Biochemistry and Molecular Biophysics, Columbia University, HHSC 1310C, 701 W, 168th St,, New York, NY 10032, USA. spg1@columbia.edu.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Goff
mesh_terms: D000818:Animals; D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics; D053595:Embryonic Stem Cells / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000235:genetics; D020868:Gene Silencing; D005822:Genetic Vectors; D016679:Genome, Viral / Q000235:genetics*; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics; D041681:NIH 3T3 Cells; D012190:Retroviridae / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D004279:DNA, Viral
references.citation: Methods Enzymol. 2011;497:603-22
references.pmid: 21601105
references.citation: Cell. 1977 Dec;12(4):963-72
references.pmid: 597866
references.citation: Nature. 2012 Jul 5;487(7405):57-63
references.pmid: 22722858
references.citation: PLoS Biol. 2013;11(4):e1001528
references.pmid: 23565060
references.citation: Proc Natl Acad Sci U S A. 1984 Nov;81(21):6627-31
references.pmid: 6593721
references.citation: Science. 2004 Jun 18;304(5678):1811-4
references.pmid: 15166317
references.citation: Mol Cell Biol. 1991 Mar;11(3):1214-21
references.pmid: 1996087
references.citation: Genes Dev. 2009 Aug 15;23(16):1870-5
references.pmid: 19684110
references.citation: Science. 2007 Jul 27;317(5837):526-9
references.pmid: 17569828
references.citation: Nature. 2009 Apr 30;458(7242):1201-4
references.pmid: 19270682
references.citation: PLoS One. 2011 Apr 29;6(4):e19355
references.pmid: 21559406
references.citation: EMBO Rep. 2013 Jan;14(1):73-9
references.pmid: 23154467
references.citation: Cell. 2007 Oct 5;131(1):46-57
references.pmid: 17923087
references.citation: Cell. 2011 Mar 18;144(6):910-25
references.pmid: 21414483
references.citation: Curr Opin Cell Biol. 2011 Dec;23(6):650-6
references.pmid: 21982544
references.citation: J Cell Physiol. 1975 Apr;85(2 Pt 1):179-87
references.pmid: 164473
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8780-5
references.pmid: 16728505
references.citation: Cell Stem Cell. 2008 Oct 9;3(4):391-401
references.pmid: 18940731
references.citation: J Biol Chem. 1979 Nov 10;254(21):10979-85
references.pmid: 115865
references.citation: J Virol. 2007 Mar;81(6):2592-604
references.pmid: 17202206
references.citation: Proc Natl Acad Sci U S A. 1973 Oct;70(10):2988-92
references.pmid: 4355379
references.citation: Proc Natl Acad Sci U S A. 1973 Dec;70(12):3899-903
references.pmid: 4521215
references.citation: Cell Tissue Res. 2011 Oct;346(1):43-51
references.pmid: 21987218
references.citation: Proc Natl Acad Sci U S A. 1985 Apr;82(8):2422-6
references.pmid: 3857593
references.citation: Mol Cell. 2011 Feb 18;41(4):480-92
references.pmid: 21329885
references.citation: Epigenetics Chromatin. 2010 Sep 24;3(1):17
references.pmid: 20868487
references.citation: Retrovirology. 2012 Dec 20;9:111
references.pmid: 23253934
references.citation: Nature. 2010 Jan 14;463(7278):237-40
references.pmid: 20075919
references.citation: Mol Cell Biol. 2000 Oct;20(20):7419-26
references.pmid: 11003639
references.citation: Rev Med Virol. 2001 Jul-Aug;11(4):205-17
references.pmid: 11479927
references.citation: Cell. 1977 Dec;12(4):973-82
references.pmid: 202395
references.citation: Nature. 2007 Dec 20;450(7173):1230-4
references.pmid: 18097409
references.citation: Cell. 1986 Nov 7;47(3):391-9
references.pmid: 3768959