Genome-wide DNA hypomethylation and RNA:DNA hybrid accumulation in Aicardi–Goutières syndrome

eLife

Volumn 4, Issue JULY2015, 2015, Pages

  Lim, Yoong Wearn ^a   Sanz, Lionel A ^a   Xu, Xiaoqin ^a   Hartono, Stella R ^a   Chédin, Frédéric ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AICARDI GOUTIERES SYNDROME; ARTICLE; CONTROLLED STUDY; DNA METHYLATION; DNA NICK TRANSLATION; EPIGENETICS; ESCHERICHIA COLI; GENE EXPRESSION; HUMAN; IMMUNE SYSTEM; INFLAMMATION; NONHUMAN; POLYMERASE CHAIN REACTION; SEQUENCE ANALYSIS; SYSTEMIC LUPUS ERYTHEMATOSUS; WESTERN BLOTTING; CELL CULTURE; FIBROBLAST; GENETIC EPIGENESIS; GENETICS; IMMUNOLOGY; METABOLISM; NERVOUS SYSTEM MALFORMATION; NEUROLOGIC DISEASE; PATHOLOGY;

DNA; IMMUNOLOGIC FACTOR; RNA;

AUTOIMMUNE DISEASES OF THE NERVOUS SYSTEM; CELLS, CULTURED; DNA; DNA METHYLATION; EPIGENESIS, GENETIC; FIBROBLASTS; HUMANS; IMMUNOLOGIC FACTORS; NERVOUS SYSTEM MALFORMATIONS; RNA;

EID: 84938907605     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.08007     Document Type: Article

References (85)

1. Absher DM, Li X, Waite LL, Gibson A, Roberts K, Edberg J, Chatham WW, Kimberly RP. 2013. Genome-wide DNA methylation analysis of systemic lupus erythematosus reveals persistent hypomethylation of interferon genes and compositional changes to CD4+ T-cell populations. PLOS Genetics 9:e1003678. doi: 10.1371/journal.pgen. 1003678.
2. Aguilera A, Garcia-Muse T. 2012. R loops: from transcription byproducts to threats to genome stability. Molecular Cell 46:115-124. doi: 10.1016/j.molcel.2012.04.009.
3. Anders S, Huber W. 2010. Differential expression analysis for sequence count data. Genome Biology 11:R106. doi: 10.1186/gb-2010-11-10-r106.
4. Aronesty E. 2011. Command-line tools for processing biological sequencing data.
5. Baechler EC, Batliwalla FM, Karypis G, Gaffney PM, Ortmann WA, Espe KJ, Shark KB, Grande WJ, Hughes KM, Kapur V, Gregersen PK, Behrens TW. 2003. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A 100:2610-2615. doi: 10.1073/pnas.0337679100.
6. Ballestar E, Esteller M, Richardson BC. 2006. The epigenetic face of systemic lupus erythematosus. The Journal of Immunology 176:7143-7147. doi: 10.4049/jimmunol.176.12.7143.
7. Berman BP, Weisenberger DJ, Aman JF, Hinoue T, Ramjan Z, Liu Y, Noushmehr H, Lange CP, van Dijk CM, Tollenaar RA, van den Berg D, Laird PW. 2012. Regions of focal DNA hypermethylation and long-range hypomethylation in colorectal cancer coincide with nuclear lamina-associated domains. Nature Genetics 44: 40-46. doi: 10.1038/ng.969.
8. Bestor TH, Edwards JR, Boulard M. 2015. Notes on the role of dynamic DNA methylation in mammalian development. Proceedings of the National Academy of Sciences of USA 112:6796-6799. doi: 10.1073/pnas.1415301111.
9. Bubeck D, Reijns MA, Graham SC, Astell KR, Jones EY, Jackson AP. 2011. PCNA directs type 2 RNase H activity on DNA replication and repair substrates. Nucleic Acids Research 39:3652-3666. doi: 10.1093/nar/gkq980.
10. Cerritelli SM, Crouch RJ. 2009. Ribonuclease H: the enzymes in eukaryotes. The FEBS Journal 276:1494-1505. doi: 10.1111/j.1742-4658.2009.06908.x.
11. Chen T, Hevi S, Gay F, Tsujimoto N, He T, Zhang B, Ueda Y, Li E. 2007. Complete inactivation of DNMT1 leads to mitotic catastrophe in human cancer cells. Nature Genetics 39:391-396. doi: 10.1038/ng1982.
12. Clifford R, Louis T, Robbe P, Ackroyd S, Burns A, Timbs AT, Wright Colopy G, Dreau H, Sigaux F, Judde JG, Rotger M, Telenti A, Lin YL, Pasero P, Maelfait J, Titsias M, Cohen DR, Henderson SJ, Ross MT, Bentley D, Hillmen P, Pettitt A, Rehwinkel J, Knight SJ, Taylor JC, Crow YJ, Benkirane M, Schuh A. 2014. SAMHD1 is mutated recurrently in chronic lymphocytic leukemia and is involved in response to DNA damage. Blood 123:1021-1031. doi: 10.1182/blood-2013-04-490847.
13. Crow YJ. 2011. Type I interferonopathies: a novel set of inborn errors of immunity. Annals of the New York Academy of Sciences 1238:91-98. doi: 10.1111/j.1749-6632.2011.06220.x.
14. Crow YJ, Hayward BE, Parmar R, Robins P, Leitch A, Ali M, Black DN, van Bokhoven H, Brunner HG, Hamel BC, Corry PC, Cowan FM, Frints SG, Klepper J, Livingston JH, Lynch SA, Massey RF, Meritet JF, Michaud JL, Ponsot G, Voit T, Lebon P, Bonthron DT, Jackson AP, Barnes DE, Lindahl T. 2006a. Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 cause Aicardi-Goutieres syndrome at the AGS1 locus. Nature Genetics 38: 917-920. doi: 10.1038/ng1845.
15. Crow YJ, Leitch A, Hayward BE, Garner A, Parmar R, Griffith E, AliM, Semple C, Aicardi J, Babul-Hirji R, Baumann C, Baxter P, Bertini E, Chandler KE, Chitayat D, Cau D, Dery C, Fazzi E, Goizet C, King MD, Klepper J, Lacombe D, Lanzi G, Lyall H, Martinez-Frias ML, Mathieu M, Mckeown C, Monier A, Oade Y, Quarrell OW, Rittey CD, Rogers RC, Sanchis A, Stephenson JB, Tacke U, Till M, Tolmie JL, Tomlin P, Voit T, Weschke B, Woods CG, Lebon P, Bonthron DT, Ponting CP, Jackson AP. 2006b. Mutations in genes encoding ribonuclease H2 subunits cause Aicardi-Goutieres syndrome and mimic congenital viral brain infection. Nature Genetics 38:910-916. doi: 10.1038/ng1842.
16. Crow YJ, Rehwinkel J. 2009. Aicardi-Goutieres syndrome and related phenotypes: linking nucleic acid metabolism with autoimmunity. Human Molecular Genetics 18:R130-R136. doi: 10.1093/hmg/ddp293.
17. Ginno PA, Lim YW, Lott PL, Korf I, Chedin F. 2013. GC skew at the 5′ and 3′ ends of human genes links R-loop formation to epigenetic regulation and transcription termination. Genome Research 23:1590-1600. doi: 10.1101/gr.158436.113.
18. Ginno PA, Lott PL, Christensen HC, Korf I, Chedin F. 2012. R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters. Molecular Cell 45:814-825. doi: 10.1016/j.molcel.2012.01.017.
19. Goldstone DC, Ennis-Adeniran V, Hedden JJ, Groom HC, Rice GI, Christodoulou E, Walker PA, Kelly G, Haire LF, Yap MW, de Carvalho LP, Stoye JP, Crow YJ, Taylor IA, Webb M. 2011. HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. Nature 480:379-382. doi: 10.1038/nature10623.
20. Gunther C, Kind B, Reijns MA, Berndt N, Martinez-Bueno M, Wolf C, Tungler V, Chara O, Lee YA, Hubner N, Bicknell L, Blum S, Krug C, Schmidt F, Kretschmer S, Koss S, Astell KR, Ramantani G, Bauerfeind A, Morris DL, Cunninghame Graham DS, Bubeck D, Leitch A, Ralston SH, Blackburn EA, Gahr M, Witte T, Vyse TJ, Melchers I, Mangold E, Nothen MM, Aringer M, Kuhn A, Luthke K, Unger L, Bley A, Lorenzi A, Isaacs JD, Alexopoulou D, Conrad K, Dahl A, Roers A, Alarcon-Riquelme ME, Jackson AP, Lee-Kirsch MA. 2015. Defective removal of ribonucleotides from DNA promotes systemic autoimmunity. The Journal of Clinical Investigation 125:413-424. doi: 10.1172/JCI78001.
21. Hartlova A, Erttmann SF, Raffi FA, Schmalz AM, Resch U, Anugula S, Lienenklaus S, Nilsson LM, Kroger A, Nilsson JA, Ek T, Weiss S, Gekara NO. 2015. DNA damage Primes the type I interferon system via the cytosolic DNA sensor STING to Promote anti-Microbial innate immunity. Immunity 42:332-343. doi: 10. 1016/j.immuni.2015.01.012.
22. Hawkins RD, Hon GC, Lee LK, Ngo Q, Lister R, Pelizzola M, Edsall LE, Kuan S, Luu Y, Klugman S, Antosiewicz-Bourget J, Ye Z, Espinoza C, Agarwahl S, Shen L, Ruotti V, Wang W, Stewart R, Thomson JA, Ecker JR, Ren B. 2010. Distinct epigenomic landscapes of pluripotent and lineage-committed human cells. Cell Stem Cell 6: 479-491. doi: 10.1016/j.stem.2010.03.018.
23. Hemmi H, Takeuchi O, Kawai T, Kaisho T, Sato S, Sanjo H, Matsumoto M, Hoshino K, Wagner H, Takeda K, Akira S. 2000. A Toll-like receptor recognizes bacterial DNA. Nature 408:740-745. doi: 10.1038/35047123.
24. Hiller B, Achleitner M, Glage S, Naumann R, Behrendt R, Roers A. 2012. Mammalian RNase H2 removes ribonucleotides from DNA to maintain genome integrity. The Journal of Experimental Medicine 209:1419-1426. doi: 10.1084/jem.20120876.
25. Huang da W, Sherman BT, Lempicki RA. 2009. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols 4:44-57. doi: 10.1038/nprot.2008.211.
26. Jackson-Grusby L, Beard C, Possemato R, Tudor M, Fambrough D, Csankovszki G, Dausman J, Lee P, Wilson C, Lander E, Jaenisch R. 2001. Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation. Nature Genetics 27:31-39. doi: 10.1038/83730.
27. Javierre BM, Fernandez AF, Richter J, Al-Shahrour F, Martin-Subero JI, Rodriguez-Ubreva J, Berdasco M, Fraga MF, O'Hanlon TP, Rider LG, Jacinto FV, Lopez-Longo FJ, Dopazo J, Forn M, Peinado MA, Carreno L, Sawalha AH, Harley JB, Siebert R, Esteller M, Miller FW, Ballestar E. 2010. Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus. Genome Research 20: 170-179. doi: 10.1101/gr.100289.109.
28. Jeffries MA, Dozmorov M, Tang Y, Merrill JT, Wren JD, Sawalha AH. 2011. Genome-wide DNA methylation patterns in CD4+ T cells from patients with systemic lupus erythematosus. Epigenetics 6:593-601. doi: 10.4161/epi.6.5.15374.
29. Karpf AR, Peterson PW, Rawlins JT, Dalley BK, Yang Q, Albertsen H, Jones DA. 1999. Inhibition of DNA methyltransferase stimulates the expression of signal transducer and activator of transcription 1, 2, and 3 genes in colon tumor cells. Proceedings of the National Academy of Sciences of USA 96:14007-14012. doi: 10.1073/pnas.96.24.14007.
30. Keskin H, Shen Y, Huang F, Patel M, Yang T, Ashley K, Mazin AV, Storici F. 2014. Transcript-RNA-templated DNA recombination and repair. Nature 515:436-439. doi: 10.1038/nature13682.
31. Kondo T, Kobayashi J, Saitoh T, Maruyama K, Ishii KJ, Barber GN, Komatsu K, Akira S, Kawai T. 2013. DNA damage sensor MRE11 recognizes cytosolic double-stranded DNA and induces type I interferon by regulating STING trafficking. Proceedings of the National Academy of Sciences of USA 110:2969-2974. doi: 10.1073/pnas. 1222694110.
32. Kretschmer S, Wolf C, Konig N, Staroske W, Guck J, Hausler M, Luksch H, Nguyen LA, Kim B, Alexopoulou D, Dahl A, Rapp A, Cardoso MC, Shevchenko A, Lee-Kirsch MA. 2015. SAMHD1 prevents autoimmunity by maintaining genome stability. Annals of the Rheumatic Diseases 74:e17. doi: 10.1136/annrheumdis-2013-204845.
33. Krueger F. 2014. Trim Galore [Online]. Available: http://www.bioinformatics.babraham.ac.uk/projects/trim_galore/[Accessed April 28, 2014].
34. Krueger F, Andrews SR. 2011. Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications. Bioinformatics 27:1571-1572. doi: 10.1093/bioinformatics/btr167.
35. Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D, Jones SJ, Marra MA. 2009. Circos: an information aesthetic for comparative genomics. Genome Research 19:1639-1645. doi: 10.1101/gr.092759.109.
36. Law JA, Jacobsen SE. 2010. Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nature Reviews. Genetics 11:204-220. doi: 10.1038/nrg2719.
37. Lee-Kirsch MA, Gong M, Chowdhury D, Senenko L, Engel K, Lee YA, de Silva U, Bailey SL, Witte T, Vyse TJ, Kere J, Pfeiffer C, Harvey S, Wong A, Koskenmies S, Hummel O, Rohde K, Schmidt RE, Dominiczak AF, Gahr M, Hollis T, Perrino FW, Lieberman J, Hubner N. 2007. Mutations in the gene encoding the 3′-5′ DNA exonuclease TREX1 are associated with systemic lupus erythematosus. Nature Genetics 39:1065-1067. doi: 10.1038/ng2091.
38. Leonhardt H, Page AW, Weier HU, Bestor TH. 1992. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 71:865-873. doi: 10.1016/0092-8674(92)90561-P.
39. Li E, Bestor TH, Jaenisch R. 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69:915-926. doi: 10.1016/0092-8674(92)90611-F.
40. Li H, Durbin R. 2009. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: 1754-1760. doi: 10.1093/bioinformatics/btp324.
41. Liao J, Karnik R, Gu H, Ziller MJ, Clement K, Tsankov AM, Akopian V, Gifford CA, Donaghey J, Galonska C, Pop R, Reyon D, Tsai SQ, Mallard W, Joung JK, Rinn JL, Gnirke A, Meissner A. 2015. Targeted disruption of DNMT1, DNMT3A and DNMT3B in human embryonic stem cells. Nature Genetics 47:469-478. doi: 10.1038/ng.3258.
42. Lim YW. 2015. DRIP-seq, RNA-seq and MethylC-seq datasets. NCBI Gene Expression Omnibus GSE57353. http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57353.
43. Lister R, Pelizzola M, Dowen RH, Hawkins RD, Hon G, Tonti-Filippini J, Nery JR, Lee L, Ye Z, Ngo QM, Edsall L, Antosiewicz-Bourget J, Stewart R, Ruotti V, Millar AH, Thomson JA, Ren B, Ecker JR. 2009. Human DNA methylomes at base resolution show widespread epigenomic differences. Nature 462:315-322. doi: 10.1038/nature08514.
44. Loomis EW, Sanz LA, Chedin F, Hagerman PJ. 2014. Transcription-associated R-loop formation across the human FMR1 CGG-repeat region. PLOS Genetics 10:e1004294. doi: 10.1371/journal.pgen.1004294.
45. Lott PC, Korf I. 2014. StochHMM: a flexible hidden Markov model tool and C++ library. Bioinformatics 30: 1625-1626. doi: 10.1093/bioinformatics/btu057.
46. Mankan AK, Schmidt T, Chauhan D, Goldeck M, Honing K, Gaidt M, Kubarenko AV, Andreeva L, Hopfner KP, Hornung V. 2014. Cytosolic RNA: DNA hybrids activate the cGAS-STING axis. The EMBO Journal 33:2937-2946. doi: 10.15252/embj.201488726.
47. Nick Mcelhinny SA, Kumar D, Clark AB, Watt DL, Watts BE, Lundstrom EB, Johansson E, Chabes A, Kunkel TA. 2010. Genome instability due to ribonucleotide incorporation into DNA. Nature Chemical Biology 6:774-781. doi: 10.1038/nchembio.424.
48. Orta ML, Calderon-Montano JM, Dominguez I, Pastor N, Burgos-Moron E, Lopez-Lazaro M, Cortes F, Mateos S, Helleday T. 2013. 5-Aza-2′-deoxycytidine causes replication lesions that require Fanconi anemia-dependent homologous recombination for repair. Nucleic Acids Research 41:5827-5836. doi: 10.1093/nar/gkt270.
49. Palii SS, van Emburgh BO, Sankpal UT, Brown KD, Robertson KD. 2008. DNA methylation inhibitor 5-Aza-2′- deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Molecular and Cellular Biology 28:752-771. doi: 10.1128/MCB.01799-07.
50. Poleshko A, Einarson MB, Shalginskikh N, Zhang R, Adams PD, Skalka AM, Katz RA. 2010. Identification of a functional network of human epigenetic silencing factors. The Journal of Biological Chemistry 285:422-433. doi: 10.1074/jbc.M109.064667.
51. Quddus J, Johnson KJ, Gavalchin J, Amento EP, Chrisp CE, Yung RL, Richardson BC. 1993. Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice. The Journal of Clinical Investigation 92:38-53. doi: 10.1172/JCI116576.
52. Quinlan AR, Hall IM. 2010. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26: 841-842. doi: 10.1093/bioinformatics/btq033.
53. Ravenscroft JC, Suri M, Rice GI, Szynkiewicz M, Crow YJ. 2011. Autosomal dominant inheritance of a heterozygous mutation in SAMHD1 causing familial chilblain lupus. American Journal of Medical Genetics. Part A 155A:235-237. doi: 10.1002/ajmg.a.33778.
54. Reijns MAM, Rabe B, Rigby RE, Mill P, Astell KR, Lettice LA, Boyle S, Leitch A, Keighren M, Kilanowski F, Devenney PS, Sexton D, Grimes G, Holt IJ, Hill RE, Taylor MS, Lawson KA, Dorin JR, Jackson AP. 2012. Enzymatic removal of ribonucleotides from DNA is Essential for mammalian genome integrity and development. Cell 149: 1008-1022. doi: 10.1016/j.cell.2012.04.011.
55. Rice G, Newman WG, Dean J, Patrick T, Parmar R, Flintoff K, Robins P, Harvey S, Hollis T, O'Hara A, Herrick AL, Bowden AP, Perrino FW, Lindahl T, Barnes DE, Crow YJ. 2007a. Heterozygous mutations in TREX1 cause familial chilblain lupus and dominant Aicardi-Goutieres syndrome. American Journal of Human Genetics 80:811-815. doi: 10.1086/513443.
56. Rice G, Patrick T, Parmar R, Taylor CF, Aeby A, Aicardi J, Artuch R, Montalto SA, Bacino CA, Barroso B, Baxter P, Benko WS, Bergmann C, Bertini E, Biancheri R, Blair EM, Blau N, Bonthron DT, Briggs T, Brueton LA, Brunner HG, Burke CJ, Carr IM, Carvalho DR, Chandler KE, Christen HJ, Corry PC, Cowan FM, Cox H, D'Arrigo S, Dean J, de Laet C, de Praeter C, Dery C, Ferrie CD, Flintoff K, Frints SG, Garcia-Cazorla A, Gener B, Goizet C, Goutieres F, Green AJ, Guet A, Hamel BC, Hayward BE, Heiberg A, Hennekam RC, Husson M, Jackson AP, Jayatunga R, Jiang YH, Kant SG, Kao A, King MD, Kingston HM, Klepper J, van der Knaap MS, Kornberg AJ, Kotzot D, Kratzer W, Lacombe D, Lagae L, Landrieu PG, Lanzi G, Leitch A, LimMJ, Livingston JH, Lourenco CM, Lyall EG, Lynch SA, Lyons MJ, Marom D, Mcclure JP, Mcwilliam R, Melancon SB, Mewasingh LD, Moutard ML, Nischal KK, Ostergaard JR, Prendiville J, Rasmussen M, Rogers RC, Roland D, Rosser EM, Rostasy K, Roubertie A, Sanchis A, Schiffmann R, Scholl-Burgi S, Seal S, Shalev SA, Corcoles CS, Sinha GP, Soler D, Spiegel R, Stephenson JB, Tacke U, Tan TY, Till M, Tolmie JL, Tomlin P, Vagnarelli F, Valente EM, Van Coster RN, Van der Aa N, Vanderver A, Vles JS, Voit T, Wassmer E, Weschke B, Whiteford ML, Willemsen MA, Zankl A, Zuberi SM, Orcesi S, Fazzi E, Lebon P, Crow YJ. 2007b. Clinical and molecular phenotype of Aicardi-Goutieres syndrome. American Journal of Human Genetics 81:713-725. doi: 10.1086/521373.
57. Rice GI, Bond J, Asipu A, Brunette RL, Manfield IW, Carr IM, Fuller JC, Jackson RM, Lamb T, Briggs TA, Ali M, Gornall H, Couthard LR, Aeby A, Attard-Montalto SP, Bertini E, Bodemer C, Brockmann K, Brueton LA, Corry PC, Desguerre I, Fazzi E, Cazorla AG, Gener B, Hamel BC, Heiberg A, Hunter M, van der Knaap MS, Kumar R, Lagae L, Landrieu PG, Lourenco CM, Marom D, Mcdermott MF, van der Merwe W, Orcesi S, Prendiville JS, Rasmussen M, Shalev SA, Soler DM, Shinawi M, Spiegel R, Tan TY, Vanderver A, Wakeling EL, Wassmer E, Whittaker E, Lebon P, Stetson DB, Bonthron DT, Crow YJ. 2009. Mutations involved in Aicardi-Goutieres syndrome implicate SAMHD1 as regulator of the innate immune response. Nature Genetics 41:829-832. doi: 10.1038/ng.373.
58. Rice GI, Del Toro Duany Y, Jenkinson EM, Forte GM, Anderson BH, Ariaudo G, Bader-Meunier B, Baildam EM, Battini R, Beresford MW, Casarano M, Chouchane M, Cimaz R, Collins AE, Cordeiro NJ, Dale RC, Davidson JE, de Waele L, Desguerre I, Faivre L, Fazzi E, Isidor B, Lagae L, Latchman AR, Lebon P, Li C, Livingston JH, Lourenco CM, Mancardi MM, Masurel-Paulet A, Mcinnes IB, Menezes MP, Mignot C, O'Sullivan J, Orcesi S, Picco PP, Riva E, Robinson RA, Rodriguez D, Salvatici E, Scott C, Szybowska M, Tolmie JL, Vanderver A, Vanhulle C, Vieira JP, Webb K, Whitney RN, Williams SG, Wolfe LA, Zuberi SM, Hur S, Crow YJ. 2014. Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling. Nature Genetics 46:503-509. doi: 10.1038/ng.2933.
59. Rice GI, Forte GM, Szynkiewicz M, Chase DS, Aeby A, Abdel-Hamid MS, Ackroyd S, Allcock R, Bailey KM, Balottin U, Barnerias C, Bernard G, Bodemer C, Botella MP, Cereda C, Chandler KE, Dabydeen L, Dale RC, de Laet C, de Goede CG, Del Toro M, Effat L, Enamorado NN, Fazzi E, Gener B, Haldre M, Lin JP, Livingston JH, Lourenco CM, Marques W jr, Oades P, Peterson P, Rasmussen M, Roubertie A, Schmidt JL, Shalev SA, Simon R, Spiegel R, Swoboda KJ, Temtamy SA, Vassallo G, Vilain CN, Vogt J, Wermenbol V, Whitehouse WP, Soler D, Olivieri I, Orcesi S, Aglan MS, Zaki MS, Abdel-Salam GM, Vanderver A, Kisand K, Rozenberg F, Lebon P, Crow YJ. 2013. Assessment of interferon-related biomarkers in Aicardi-Goutieres syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurology 12: 1159-1169. doi: 10.1016/S1474-4422(13)70258-8.
60. Rice GI, Kasher PR, Forte GM, Mannion NM, Greenwood SM, Szynkiewicz M, Dickerson JE, Bhaskar SS, Zampini M, Briggs TA, Jenkinson EM, Bacino CA, Battini R, Bertini E, Brogan PA, Brueton LA, Carpanelli M, de Laet C, de Lonlay P, Del Toro M, Desguerre I, Fazzi E, Garcia-Cazorla A, Heiberg A, Kawaguchi M, Kumar R, Lin JP, Lourenco CM, Male AM, Marques W jr, Mignot C, Olivieri I, Orcesi S, Prabhakar P, Rasmussen M, Robinson RA, Rozenberg F, Schmidt JL, Steindl K, Tan TY, van der Merwe WG, Vanderver A, Vassallo G, Wakeling EL, Wassmer E, Whittaker E, Livingston JH, Lebon P, Suzuki T, Mclaughlin PJ, Keegan LP, O'Connell MA, Lovell SC, Crow YJ. 2012. Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature. Nature Genetics 44:1243-1248. doi: 10.1038/ng.2414.
61. Richardson B. 1986. Effect of an inhibitor of DNA methylation on T cells. II. 5-Azacytidine induces self-reactivity in antigen-specific T4+ cells. Human Immunology 17:456-470. doi: 10.1016/0198-8859(86)90304-6.
62. Richardson B, Scheinbart L, Strahler J, Gross L, Hanash S, Johnson M. 1990. Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum 33:1665-1673. doi: 10. 1002/art.1780331109.
63. Rigby RE, Webb LM, Mackenzie KJ, Li Y, Leitch A, Reijns MA, Lundie RJ, Revuelta A, Davidson DJ, Diebold S, Modis Y, Macdonald AS, Jackson AP. 2014. RNA: DNA hybrids are a novel molecular pattern sensed by TLR9. The EMBO Journal 33:542-558. doi: 10.1002/embj.201386117.
64. Sarkies P, Reams C, Simpson LJ, Sale JE. 2010. Epigenetic instability due to defective replication of structured DNA. Molecular Cell 40:703-713. doi: 10.1016/j.molcel.2010.11.009.
65. Schermelleh L, Haemmer A, Spada F, Rosing N, Meilinger D, Rothbauer U, Cardoso MC, Leonhardt H. 2007. Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation. Nucleic Acids Research 35:4301-4312. doi: 10.1093/nar/gkm432.
66. Schroeder DI, Blair JD, Lott P, Yu HO, Hong D, Crary F, Ashwood P, Walker C, Korf I, Robinson WP, Lasalle JM. 2013. The human placenta methylome. Proceedings of the National Academy of Sciences of USA 110:6037-6042. doi: 10.1073/pnas.1215145110.
67. Schroeder DI, Lott P, Korf I, Lasalle JM. 2011. Large-scale methylation domains mark a functional subset of neuronally expressed genes. Genome Research 21:1583-1591. doi: 10.1101/gr.119131.110.
68. Stetson DB, Ko JS, Heidmann T, Medzhitov R. 2008. Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 134:587-598. doi: 10.1016/j.cell.2008.06.032.
69. Sun L, Wu J, Du F, Chen X, Chen ZJ. 2013. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339:786-791. doi: 10.1126/science.1232458.
70. Trapnell C, Pachter L, Salzberg SL. 2009. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25: 1105-1111. doi: 10.1093/bioinformatics/btp120.
71. Tsumura A, Hayakawa T, Kumaki Y, Takebayashi S, Sakaue M, Matsuoka C, Shimotohno K, Ishikawa F, Li E, Ueda HR, Nakayama J, Okano M. 2006. Maintenance of self-renewal ability of mouse embryonic stem cells in the absence of DNA methyltransferases Dnmt1, Dnmt3a and Dnmt3b. Genes To Cells 11:805-814. doi: 10.1111/j. 1365-2443.2006.00984.x.
72. Tuller T, Atar S, Ruppin E, Gurevich M, Achiron A. 2013. Common and specific signatures of gene expression and protein-protein interactions in autoimmune diseases. Genes and Immunity 14:67-82. doi: 10.1038/gene.2012.55.
73. Varley KE, Gertz J, Bowling KM, Parker SL, Reddy TE, Pauli-Behn F, Cross MK, Williams BA, Stamatoyannopoulos JA, Crawford GE, Absher DM, Wold BJ, Myers RM. 2013. Dynamic DNA methylation across diverse human cell lines and tissues. Genome Research 23:555-567. doi: 10.1101/gr.147942.112.
74. Volkman HE, Stetson DB. 2014. The enemy within: endogenous retroelements and autoimmune disease. Nature Immunology 15:415-422. doi: 10.1038/ni.2872.
75. Walsh CP, Chaillet JR, Bestor TH. 1998. Transcription of IAP endogenous retroviruses is constrained by cytosine methylation. Nature Genetics 20:116-117. doi: 10.1038/2413.
76. Yang YG, Lindahl T, Barnes DE. 2007. Trex1 exonuclease degrades ssDNA to prevent chronic checkpoint activation and autoimmune disease. Cell 131:873-886. doi: 10.1016/j.cell.2007.10.017.
77. Yoder JA, Bestor TH. 1998. A candidate mammalian DNA methyltransferase related to pmt1p of fission yeast. Human Molecular Genetics 7:279-284. doi: 10.1093/hmg/7.2.279.
78. Yoder JA, Walsh CP, Bestor TH. 1997. Cytosine methylation and the ecology of intragenomic parasites. Trends in Genetics 13:335-340. doi: 10.1016/S0168-9525(97)01181-5.
79. Yu C, Gan H, Han J, Zhou ZX, Jia S, Chabes A, Farrugia G, Ordog T, Zhang Z. 2014. Strand-specific analysis shows protein binding at replication Forks and PCNA unloading from lagging strands when Forks Stall. Molecular Cell 56:551-563. doi: 10.1016/j.molcel.2014.09.017.
80. Yung RL, Quddus J, Chrisp CE, Johnson KJ, Richardson BC. 1995. Mechanism of drug-induced lupus. I. Cloned Th2 cells modified with DNA methylation inhibitors in vitro cause autoimmunity in vivo. The Journal of Immunology 154:3025-3035.
81. Zhang X, Brann TW, Zhou M, Yang J, Oguariri RM, Lidie KB, Imamichi H, Huang DW, Lempicki RA, Baseler MW, Veenstra TD, Young HA, Lane HC, Imamichi T. 2011. Cutting edge: Ku70 is a novel cytosolic DNA sensor that induces type III rather than type I IFN. The Journal of Immunology 186:4541-4545. doi: 10.4049/jimmunol.1003389.
82. Zhang Y, Liu T, Meyer CA, Eeckhoute J, Johnson DS, Bernstein BE, Nusbaum C, Myers RM, Brown M, Li W, Liu XS. 2008. Model-based analysis of ChIP-Seq (MACS). Genome Biology 9:R137. doi: 10.1186/gb-2008-9-9-r137.
83. Zhang Y, Zhao M, Sawalha AH, Richardson B, Lu Q. 2013. Impaired DNA methylation and its mechanisms in CD4(+) T cells of systemic lupus erythematosus. Journal of Autoimmunity 41:92-99. doi: 10.1016/j.jaut.2013.01.005.
84. Zhao K, Du J, Han X, Goodier JL, Li P, Zhou X, Wei W, Evans SL, Li L, Zhang W, Cheung LE, Wang G, Kazazian HH Jr, Yu XF. 2013a. Modulation of LINE-1 and Alu/SVA retrotransposition by Aicardi-Goutieres syndrome-related SAMHD1. Cell Reports 4:1108-1115. doi: 10.1016/j.celrep.2013.08.019.
85. Zhao R, Zhou H, Su SB. 2013b. A critical role for interleukin-1beta in the progression of autoimmune diseases. International Immunopharmacology 17:658-669. doi: 10.1016/j.intimp.2013.08.012.