title: The frequency natural antisense transcript first promotes, then represses, frequency gene expression via facultative heterochromatin.
abstract: The circadian clock is controlled by a network of interconnected feedback loops that require histone modifications and chromatin remodeling. Long noncoding natural antisense transcripts (NATs) originate from Period in mammals and frequency (frq) in Neurospora. To understand the role of NATs in the clock, we put the frq antisense transcript qrf (frq spelled backwards) under the control of an inducible promoter. Replacing the endogenous qrf promoter altered heterochromatin formation and DNA methylation at frq. In addition, constitutive, low-level induction of qrf caused a dramatic effect on the endogenous rhythm and elevated circadian output. Surprisingly, even though qrf is needed for heterochromatic silencing, induction of qrf initially promoted frq gene expression by creating a more permissible local chromatin environment. The observation that antisense expression can initially promote sense gene expression before silencing via heterochromatin formation at convergent loci is also found when a NAT to hygromycin resistance gene is driven off the endogenous vivid (vvd) promoter in the Δvvd strain. Facultative heterochromatin silencing at frq functions in a parallel pathway to previously characterized VVD-dependent silencing and is needed to establish the appropriate circadian phase. Thus, repression via dicer-independent siRNA-mediated facultative heterochromatin is largely independent of, and occurs alongside, other feedback processes.
authors.affiliation: Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Joska
authors.affiliation: Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Ruesch
authors.affiliation: Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901.
authors.forename: Samuel J
authors.initials: SJ
authors.lastname: Coster
authors.affiliation: Department of Animal Sciences, School of Environmental and Biological Sciences, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901 belden@aesop.rutgers.edu.
authors.forename: William J
authors.initials: WJ
authors.lastname: Belden
mesh_terms: D001683:Biological Clocks / Q000235:genetics; D056926:CLOCK Proteins / Q000235:genetics; D002940:Circadian Rhythm; D019175:DNA Methylation; D005786:Gene Expression Regulation; D015966:Gene Expression Regulation, Fungal; D006570:Heterochromatin / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D009492:Neurospora crassa / Q000235:genetics* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D009991:Oscillometry; D011401:Promoter Regions, Genetic; D062085:RNA, Long Noncoding / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism
chemical_list: D006570:Heterochromatin; D006657:Histones; D016376:Oligonucleotides, Antisense; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D056926:CLOCK Proteins
keywords: DNA methylation; circadian rhythm; heterochromatin; natural antisense transcripts
references.citation: EMBO J. 2009 Apr 22;28(8):1029-42
references.pmid: 19262566
references.citation: Genes Dev. 2008 Nov 15;22(22):3196-204
references.pmid: 18997062
references.citation: Mol Cell. 2009 May 15;34(3):354-63
references.pmid: 19450533
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 30;106(26):10722-7
references.pmid: 19506251
references.citation: Methods Mol Biol. 2010;638:33-40
references.pmid: 20238259
references.citation: Mol Cell. 2010 Jun 25;38(6):803-14
references.pmid: 20417140
references.citation: Cell. 2010 Sep 3;142(5):762-72
references.pmid: 20813262
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16715-20
references.pmid: 20733070
references.citation: Proc Natl Acad Sci U S A. 2010 Sep 21;107(38):16709-14
references.pmid: 20807745
references.citation: Eukaryot Cell. 2010 Oct;9(10):1549-56
references.pmid: 20675579
references.citation: PLoS Genet. 2010 Nov;6(11):e1001196
references.pmid: 21079689
references.citation: PLoS Genet. 2011 Jul;7(7):e1002166
references.pmid: 21811413
references.citation: Science. 2012 Jan 6;335(6064):96-100
references.pmid: 22144463
references.citation: Cell. 2001 Feb 9;104(3):453-64
references.pmid: 11239402
references.citation: EMBO J. 2001 Jan 15;20(1-2):109-17
references.pmid: 11226161
references.citation: EMBO J. 2001 Aug 1;20(15):4309-23
references.pmid: 11483533
references.citation: Nature. 2001 Nov 15;414(6861):277-83
references.pmid: 11713521
references.citation: Science. 2002 Aug 2;297(5582):815-9
references.pmid: 12098706
references.citation: Nature. 2003 Feb 27;421(6926):948-52
references.pmid: 12607002
references.citation: Nat Genet. 2003 May;34(1):75-9
references.pmid: 12679815
references.citation: Proc Natl Acad Sci U S A. 2003 May 13;100(10):5914-9
references.pmid: 12714686
references.citation: EMBO J. 2003 Sep 15;22(18):4846-55
references.pmid: 12970196
references.citation: Mol Cell. 2004 Feb 13;13(3):427-34
references.pmid: 14967149
references.citation: Science. 2004 Jun 25;304(5679):1939
references.pmid: 15218142
references.citation: Science. 1994 Mar 18;263(5153):1578-84
references.pmid: 8128244
references.citation: Science. 1997 May 2;276(5313):763-9
references.pmid: 9115195
references.citation: Cell. 1997 May 2;89(3):469-76
references.pmid: 9150146
references.citation: EMBO J. 1999 Sep 15;18(18):4961-8
references.pmid: 10487748
references.citation: Genes Dev. 2005 Jan 15;19(2):234-41
references.pmid: 15625191
references.citation: Nat Rev Genet. 2005 Jul;6(7):544-56
references.pmid: 15951747
references.citation: Science. 2012 Oct 19;338(6105):349-54
references.pmid: 22936566
references.citation: Cell Metab. 2012 Dec 5;16(6):833-45
references.pmid: 23217262
references.citation: J Biol Chem. 2013 Mar 22;288(12):8380-90
references.pmid: 23319591
references.citation: Curr Opin Cell Biol. 2013 Apr;25(2):170-6
references.pmid: 23385084
references.citation: PLoS Genet. 2013;9(9):e1003761
references.pmid: 24039604
references.citation: Nat Struct Mol Biol. 2014 Feb;21(2):126-32
references.pmid: 24413057
references.citation: PLoS One. 2014;9(3):e91353
references.pmid: 24621812
references.citation: Nature. 2014 Oct 30;514(7524):650-3
references.pmid: 25132551
references.citation: G3 (Bethesda). 2014 Jan;5(1):93-101
references.pmid: 25429045
references.citation: Mol Cell. 2011 Sep 2;43(5):713-22
references.pmid: 21884974
references.citation: Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10352-7
references.pmid: 16801547
references.citation: Mol Cell. 2007 Feb 23;25(4):587-600
references.pmid: 17317630
references.citation: Adv Genet. 2007;58:25-66
references.pmid: 17452245
references.citation: Genes Dev. 2007 Jun 15;21(12):1494-505
references.pmid: 17575051
references.citation: Eukaryot Cell. 2008 Jan;7(1):28-37
references.pmid: 17766461
references.citation: Mol Microbiol. 2008 Apr;68(2):255-62
references.pmid: 18312266
references.citation: Mol Cell Biol. 2008 Oct;28(19):6044-55
references.pmid: 18678653
references.citation: Eukaryot Cell. 2009 May;8(5):800-4
references.pmid: 19286985