Methylation of C9orf72 expansion reduces RNA foci formation and dipeptide-repeat proteins expression in cells

Neuroscience Letters

Volumn 612, Issue , 2016, Pages 204-209

  Bauer, Peter O ^a  

^a MAYO GRADUATE SCHOOL   (United States)

Author keywords

Amyotrophic lateral sclerosis; C9orf72; DNA methylation; Epigenetics; Frontotemporal dementia; Repeat expansion

Indexed keywords

C9ORF72 PROTEIN, HUMAN; NUCLEAR RNA; PROTEIN; REPETITIVE DNA;

AMYOTROPHIC LATERAL SCLEROSIS; DNA METHYLATION; GENETIC EPIGENESIS; GENETICS; HEK293 CELL LINE; HUMAN; METABOLISM;

AMYOTROPHIC LATERAL SCLEROSIS; DNA METHYLATION; DNA REPEAT EXPANSION; EPIGENESIS, GENETIC; HEK293 CELLS; HUMANS; PROTEINS; RNA, NUCLEAR;

EID: 84955444375     PISSN: 03043940     EISSN: 18727972     Source Type: Journal    
DOI: 10.1016/j.neulet.2015.12.018     Document Type: Article

References (26)

1. Lillo P., Hodges J.R. Frontotemporal dementia and motor neurone disease: overlapping clinic-pathological disorders. J. Clin. Neurosci. 2009, 16:1131-1135.
2. DeJesus-Hernandez M., Mackenzie I.R., Boeve B.F., Boxer A.L., Baker M., Rutherford N.J., Nicholson A.M., Finch N.A., Flynn H., Adamson J., Kouri N., Wojtas A., Sengdy P., Hsiung G.Y., Karydas A., Seeley W.W., Josephs K.A., Coppola G., Geschwind D.H., Wszolek Z.K., Feldman H., Knopman D.S., Petersen R.C., Miller B.L., Dickson D.W., Boylan K.B., Graff-Radford N.R., Rademakers R. Expanded GGGGCC hexanucleotide repeat in noncoding region of C9ORF72 causes chromosome 9p-linked FTD and ALS. Neuron 2011, 72:245-256.
3. Renton A.E., Majounie E., Waite A., Simon-Sanchez J., Rollinson S., Gibbs J.R., Schymick J.C., Laaksovirta H., van Swieten J.C., Myllykangas L., Kalimo H., Paetau A., Abramzon Y., Remes A.M., Kaganovich A., Scholz S.W., Duckworth J., Ding J., Harmer D.W., Hernandez D.G., Johnson J.O., Mok K., Ryten M., Trabzuni D., Guerreiro R.J., Orrell R.W., Neal J., Murray A., Pearson J., Jansen I.E., Sondervan D., Seelaar H., Blake D., Young K., Halliwell N., Callister J.B., Toulson G., Richardson A., Gerhard A., Snowden J., Mann D., Neary D., Nalls M.A., Peuralinna T., Jansson L., Isoviita V.M., Kaivorinne A.L., Holtta-Vuori M., Ikonen E., Sulkava R., Benatar M., Wuu J., Chio A., Restagno G., Borghero G., Sabatelli M., Heckerman D., Rogaeva E., Zinman L., Rothstein J.D., Sendtner M., Drepper C., Eichler E.E., Alkan C., Abdullaev Z., Pack S.D., Dutra A., Pak E., Hardy J., Singleton A., Williams N.M., Heutink P., Pickering-Brown S., Morris H.R., Tienari P.J., Traynor B.J. A hexanucleotide repeat expansion in C9ORF72 is the cause of chromosome 9p21-linked ALS-FTD. Neuron 2011, 72:257-268.
4. Waite A.J., Baumer D., East S., Neal J., Morris H.R., Ansorge O., Blake D.J. Reduced C9orf72 protein levels in frontal cortex of amyotrophic lateral sclerosis and frontotemporal degeneration brain with the C9ORF72 hexanucleotide repeat expansion. Neurobiol. Aging 2014, 35:1779.e5-1779.e13.
5. Levine T.P., Daniels R.D., Gatta A.T., Wong L.H., Hayes M.J. The product of C9orf72, a gene strongly implicated in neurodegeneration, is structurally related to DENN Rab-GEFs. Bioinformatics 2013, 29:499-503.
6. Zhang D., Iyer L.M., He F., Aravind L. Discovery of novel DENN proteins: implications for the evolution of eukaryotic intracellular membrane structures and human disease. Front. Genet. 2012, 3:283.
7. Lagier-Tourenne C., Baughn M., Rigo F., Sun S., Liu P., Li H.R., Jiang J., Watt A.T., Chun S., Katz M., Qiu J., Sun Y., Ling S.C., Zhu Q., Polymenidou M., Drenner K., Artates J.W., McAlonis-Downes M., Markmiller S., Hutt K.R., Pizzo D.P., Cady J., Harms M.B., Baloh R.H., Vandenberg S.R., Yeo G.W., Fu X.D., Bennett C.F., Cleveland D.W., Ravits J. Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration. Proc. Natl. Acad. Sci. U. S. A. 2013, 110:E4530-E4539.
8. Gendron T.F., Bieniek K.F., Zhang Y.J., Jansen-West K., Ash P.E., Caulfield T., Daughrity L., Dunmore J.H., Castanedes-Casey M., Chew J., Cosio D.M., van Blitterswijk M., Lee W.C., Rademakers R., Boylan K.B., Dickson D.W., Petrucelli L. Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS. Acta Neuropathol. 2013, 126:829-844.
9. Lee Y.B., Chen H.J., Peres J.N., Gomez-Deza J., Attig J., Stalekar M., Troakes C., Nishimura A.L., Scotter E.L., Vance C., Adachi Y., Sardone V., Miller J.W., Smith B.N., Gallo J.M., Ule J., Hirth F., Rogelj B., Houart C., Shaw C.E. Hexanucleotide repeats in ALS/FTD form length-dependent RNA foci, sequester RNA binding proteins, and are neurotoxic. Cell Rep. 2013, 5:1178-1186.
10. Ash P.E., Bieniek K.F., Gendron T.F., Caulfield T., Lin W.L., Dejesus-Hernandez M., van Blitterswijk M.M., Jansen-West K., Paul III J.W., Rademakers R., Boylan K.B., Dickson D.W., Petrucelli L. Unconventional translation of C9ORF72 GGGGCC expansion generates insoluble polypeptides specific to c9FTD/ALS. Neuron 2013, 77:639-646.
11. Mori K., Arzberger T., Grasser F.A., Gijselinck I., May S., Rentzsch K., Weng S.M., Schludi M.H., van der Zee J., Cruts M., Van Broeckhoven C., Kremmer E., Kretzschmar H.A., Haass C., Edbauer D. Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins. Acta Neuropathol. 2013, 126:881-893.
12. Belzil V.V., Bauer P.O., Prudencio M., Gendron T.F., Stetler C.T., Yan I.K., Pregent L., Daughrity L., Baker M.C., Rademakers R., Boylan K., Patel T.C., Dickson D.W., Petrucelli L. Reduced C9orf72 gene expression in c9FTD/ALS is caused by histone trimethylation, an epigenetic event detectable in blood. Acta Neuropathol. 2013, 126:895-905.
13. Liu E.Y., Russ J., Wu K., Neal D., Suh E., McNally A.G., Irwin D.J., Van Deerlin V.M., Lee E.B. C9orf72 hypermethylation protects against repeat expansion-associated pathology in ALS/FTD. Acta Neuropathol. 2014, 128:525-541.
14. Xi Z., Rainero I., Rubino E., Pinessi L., Bruni A.C., Maletta R.G., Nacmias B., Sorbi S., Galimberti D., Surace E.I., Zheng Y., Moreno D., Sato C., Liang Y., Zhou Y., Robertson J., Zinman L., Tartaglia M.C., St George-Hyslop P., Rogaeva E. Hypermethylation of the CpG-island near the C9orf72 G(4)C(2)-repeat expansion in FTLD patients. Hum. Mol. Genet. 2014, 23:5630-5637.
15. Xi Z., Zinman L., Moreno D., Schymick J., Liang Y., Sato C., Zheng Y., Ghani M., Dib S., Keith J., Robertson J., Rogaeva E. Hypermethylation of the CpG island near the GC repeat in ALS with a C9orf72 expansion. Am. J. Hum. Genet. 2013, 92:981-989.
16. Xi Z., Zhang M., Bruni A.C., Maletta R.G., Colao R., Fratta P., Polke J.M., Sweeney M.G., Mudanohwo E., Nacmias B., Sorbi S., Tartaglia M.C., Rainero I., Rubino E., Pinessi L., Galimberti D., Surace E.I., McGoldrick P., McKeever P., Moreno D., Sato C., Liang Y., Keith J., Zinman L., Robertson J., Rogaeva E. The C9orf72 repeat expansion itself is methylated in ALS and FTLD patients. Acta Neuropathol. 2015, 129:715-727.
17. Belzil V.V., Bauer P.O., Gendron T.F., Murray M.E., Dickson D., Petrucelli L. Characterization of DNA hypermethylation in the cerebellum of c9FTD/ALS patients. Brain Res. 2014, 1584:15-21.
18. Russ J., Liu E.Y., Wu K., Neal D., Suh E., Irwin D.J., McMillan C.T., Harms M.B., Cairns N.J., Wood E.M., Xie S.X., Elman L., McCluskey L., Grossman M., Van Deerlin V.M., Lee E.B. Hypermethylation of repeat expanded C9orf72 is a clinical and molecular disease modifier. Acta Neuropathol. 2015, 129:39-52.
19. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002, 16:6-21.
20. Turker M.S. The establishment and maintenance of DNA methylation patterns in mouse somatic cells. Semin. Cancer Biol. 1999, 9:329-337.
21. Su Z., Zhang Y., Gendron T.F., Bauer P.O., Chew J., Yang W.Y., Fostvedt E., Jansen-West K., Belzil V.V., Desaro P., Johnston A., Overstreet K., Oh S.Y., Todd P.K., Berry J.D., Cudkowicz M.E., Boeve B.F., Dickson D., Floeter M.K., Traynor B.J., Morelli C., Ratti A., Silani V., Rademakers R., Brown R.H., Rothstein J.D., Boylan K.B., Petrucelli L., Disney M.D. Discovery of a biomarker and lead small molecules to target r(GGGGCC)-associated defects in c9FTD/ALS. Neuron 2014, 83:1043-1050.
22. Bauer P.O., Wong H.K., Oyama F., Goswami A., Okuno M., Kino Y., Miyazaki H., Nukina N. Inhibition of Rho kinases enhances the degradation of mutant huntingtin. J. Biol. Chem. 2009, 284:13153-13164.
23. Bauer P.O., Hudec R., Goswami A., Kurosawa M., Matsumoto G., Mikoshiba K., Nukina N. ROCK-phosphorylated vimentin modifies mutant huntingtin aggregation via sequestration of IRBIT. Mol. Neurodegener. 2012, 7:43.
24. Carotti D., Funiciello S., Palitti F., Strom R. Influence of pre-existing methylation on the de novo activity of eukaryotic DNA methyltransferase. Biochemistry 1998, 37:1101-1108.
25. Lindsay H., Adams R.L. Spreading of methylation along DNA. Biochem. J. 1996, 320(Pt. 2):473-478.
26. Howell C.Y., Steptoe A.L., Miller M.W., Chaillet J.R. cis-Acting signal for inheritance of imprinted DNA methylation patterns in the preimplantation mouse embryo. Mol. Cell. Biol. 1998, 18:4149-4156.