title: Methylation-sensitive expression of a DNA demethylase gene serves as an epigenetic rheostat.
abstract: Genomes must balance active suppression of transposable elements (TEs) with the need to maintain gene expression. In Arabidopsis, euchromatic TEs are targeted by RNA-directed DNA methylation (RdDM). Conversely, active DNA demethylation prevents accumulation of methylation at genes proximal to these TEs. It is unknown how a cellular balance between methylation and demethylation activities is achieved. Here we show that both RdDM and DNA demethylation are highly active at a TE proximal to the major DNA demethylase gene ROS1. Unexpectedly, and in contrast to most other genomic targets, expression of ROS1 is promoted by DNA methylation and antagonized by DNA demethylation. We demonstrate that inducing methylation in the ROS1 proximal region is sufficient to restore ROS1 expression in an RdDM mutant. Additionally, methylation-sensitive expression of ROS1 is conserved in other species, suggesting it is adaptive. We propose that the ROS1 locus functions as an epigenetic rheostat, tuning the level of demethylase activity in response to methylation alterations, thus ensuring epigenomic stability.
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.
authors.forename: Ben P
authors.initials: BP
authors.lastname: Williams
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America.
authors.forename: Daniela
authors.initials: D
authors.lastname: Pignatta
authors.affiliation: Howard Hughes Medical Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
authors.forename: Steven
authors.initials: S
authors.lastname: Henikoff
authors.affiliation: Whitehead Institute for Biomedical Research, Cambridge, Massachusetts, United States of America; Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Gehring
mesh_terms: D017360:Arabidopsis; D029681:Arabidopsis Proteins / Q000096:biosynthesis / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004251:DNA Transposable Elements / Q000235:genetics; D057890:Epigenomics; D018506:Gene Expression Regulation, Plant; D020868:Gene Silencing; D018745:Genome, Plant; D042822:Genomic Instability / Q000235:genetics; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics*; D030821:Plants, Genetically Modified; D036226:Seedlings / Q000235:genetics / Q000254:growth & development; D014158:Transcription, Genetic
chemical_list: D029681:Arabidopsis Proteins; D004251:DNA Transposable Elements; D009687:Nuclear Proteins; C471271:ROS1 protein, Arabidopsis
references.citation: Genetics. 2015 Apr;199(4):1107-25
references.pmid: 25653306
references.citation: PLoS One. 2014;9(5):e95445
references.pmid: 24810581
references.citation: Methods. 2001 Dec;25(4):402-8
references.pmid: 11846609
references.citation: J Biol Chem. 2002 Oct 4;277(40):37741-6
references.pmid: 12124387
references.citation: Cell. 2002 Dec 13;111(6):803-14
references.pmid: 12526807
references.citation: Genome Res. 2003 Mar;13(3):524-30
references.pmid: 12618384
references.citation: Bioinformatics. 2003 Aug 12;19(12):1572-4
references.pmid: 12912839
references.citation: Dev Cell. 2003 Dec;5(6):891-901
references.pmid: 14667411
references.citation: Nucleic Acids Res. 2004;32(5):1792-7
references.pmid: 15034147
references.citation: Plant Cell Physiol. 2004 Apr;45(4):490-5
references.pmid: 15111724
references.citation: EMBO J. 2004 Oct 27;23(21):4286-96
references.pmid: 15457214
references.citation: Plant J. 1998 Dec;16(6):735-43
references.pmid: 10069079
references.citation: Mol Cell. 1999 Apr;3(4):505-11
references.pmid: 10230403
references.citation: Plant Physiol. 2005 Sep;139(1):5-17
references.pmid: 16166256
references.citation: EMBO J. 2006 Jun 21;25(12):2828-36
references.pmid: 16724114
references.citation: Genes Dev. 2006 Dec 15;20(24):3407-25
references.pmid: 17182867
references.citation: Nat Genet. 2007 Jan;39(1):61-9
references.pmid: 17128275
references.citation: Proc Natl Acad Sci U S A. 2007 Apr 17;104(16):6752-7
references.pmid: 17409185
references.citation: Plant J. 2007 Aug;51(3):526-36
references.pmid: 17559516
references.citation: Cell. 2007 Sep 7;130(5):851-62
references.pmid: 17803908
references.citation: Plant Physiol. 2007 Dec;145(4):1549-57
references.pmid: 17951456
references.citation: Cell. 2008 May 2;133(3):523-36
references.pmid: 18423832
references.citation: Mol Biol Evol. 2008 Jul;25(7):1253-6
references.pmid: 18397919
references.citation: PLoS One. 2008;3(9):e3156
references.pmid: 18776934
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1660-5
references.pmid: 19164525
references.citation: Science. 2009 Jun 12;324(5933):1447-51
references.pmid: 19520961
references.citation: PLoS Genet. 2009 Nov;5(11):e1000737
references.pmid: 19936292
references.citation: Plant Cell. 2010 Apr;22(4):1074-89
references.pmid: 20407027
references.citation: Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18729-34
references.pmid: 20937895
references.citation: Nat Rev Genet. 2010 Mar;11(3):204-20
references.pmid: 20142834
references.citation: Proc Natl Acad Sci U S A. 2011 May 10;108(19):8042-7
references.pmid: 21518889
references.citation: Nat Rev Cancer. 2011 Oct;11(10):726-34
references.pmid: 21941284
references.citation: Science. 2011 Oct 21;334(6054):369-73
references.pmid: 21921155
references.citation: Nature. 2011 Dec 8;480(7376):245-9
references.pmid: 22057020
references.citation: PLoS Genet. 2012 Feb;8(2):e1002474
references.pmid: 22346759
references.citation: EMBO J. 2012 Jun 29;31(13):2981-93
references.pmid: 22580822
references.citation: Nature. 2014 Mar 6;507(7490):124-8
references.pmid: 24463519
references.citation: Nat Struct Mol Biol. 2014 Jan;21(1):64-72
references.pmid: 24336224
references.citation: Cell. 2014 May 22;157(5):1050-60
references.pmid: 24855943
references.citation: Nat Commun. 2014;5:4062
references.pmid: 24898766
references.citation: Mol Cell. 2014 Aug 7;55(3):383-96
references.pmid: 25018019
references.citation: Epigenetics. 2014 Jul;9(7):1047-59
references.pmid: 24786611
references.citation: Elife. 2014;3:e03198
references.pmid: 24994762
references.citation: Plant Cell. 2014 Jul;26(7):2746-60
references.pmid: 25035402
references.citation: Bioinformatics. 2014 Nov 15;30(22):3276-8
references.pmid: 25095880
references.citation: Plant Cell. 2014 Dec;26(12):4903-17
references.pmid: 25465407
references.citation: Plant Cell. 2014 Dec;26(12):4602-16
references.pmid: 25527708
references.citation: Genome Biol. 2014;15(9):458
references.pmid: 25228471
references.citation: Proc Natl Acad Sci U S A. 2012 Aug 7;109(32):E2183-91
references.pmid: 22733782
references.citation: Nat Struct Mol Biol. 2012 Sep;19(9):870-5
references.pmid: 22864289
references.citation: Science. 2012 Sep 14;337(6100):1360-4
references.pmid: 22984074
references.citation: Cell. 2012 Sep 28;151(1):194-205
references.pmid: 23000270
references.citation: Mol Cell. 2012 Oct 12;48(1):121-32
references.pmid: 22940247
references.citation: PLoS Genet. 2012;8(11):e1003062
references.pmid: 23209430
references.citation: Oncogene. 2013 Jan 31;32(5):663-9
references.pmid: 22391558
references.citation: Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2389-94
references.pmid: 23335630
references.citation: PLoS Genet. 2013;9(2):e1003255
references.pmid: 23408902
references.citation: Cell. 2013 Mar 28;153(1):193-205
references.pmid: 23540698
references.citation: Plant J. 2013 Jan;73(2):179-89
references.pmid: 23013441