@article{386c6e882ac04eb59fca01e90d284da5,
title = "DNMT1-interacting RNAs block gene-specific DNA methylation",
abstract = "DNA methylation was first described almost a century ago; however, the rules governing its establishment and maintenance remain elusive. Here we present data demonstrating that active transcription regulates levels of genomic methylation. We identify a novel RNA arising from the CEBPA gene locus that is critical in regulating the local DNA methylation profile. This RNA binds to DNMT1 and prevents CEBPA gene locus methylation. Deep sequencing of transcripts associated with DNMT1 combined with genome-scale methylation and expression profiling extend the generality of this finding to numerous gene loci. Collectively, these results delineate the nature of DNMT1-RNA interactions and suggest strategies for gene-selective demethylation of therapeutic targets in human diseases.",
author = "{Di Ruscio}, Annalisa and Ebralidze, {Alexander K.} and Touati Benoukraf and Giovanni Amabile and Goff, {Loyal A.} and Jolyon Terragni and Figueroa, {Maria Eugenia} and {De Figueiredo Pontes}, {Lorena Lobo} and Meritxell Alberich-Jorda and Pu Zhang and Mengchu Wu and Francesco D'Al{\`o} and Ari Melnick and Giuseppe Leone and Ebralidze, {Konstantin K.} and Sriharsa Pradhan and Rinn, {John L.} and Tenen, {Daniel G.}",
note = "Funding Information: Acknowledgements This work was supported by grants CA118316, CA66996 and HL56745 from the National Institutes of Health (NIH) to D.G.T., the Italian Foundation for Cancer Research (FIRC) {\textquoteleft}Leonino Fontana e Maria Lionello{\textquoteright} fellowship, the NIH T32 HL007917-11A1 and the Societ{\`a} Italiana di Ematologia Sperimentale (SIES) {\textquoteleft}Dr.Tito Bastianello{\textquoteright}fellowship toA.D.R.; FAMRI CIA (103063) granttoA.K.E.;Fondazione Roma {\textquoteleft}Progetto cellule staminali{\textquoteright} to G.L. and F.D{\textquoteright}A.; the American Italian Cancer Foundation Fellowship (AICF) to G.A.; Funda{\c c}{\~a}o de Amparo {\`a} Pesquisa do Estado de S{\~a}o Paulo (FAPESP)—grant no. 2011/11822-6—to L.L.D.F.P.; the National Research Foundation and the Singapore Ministry of Education under its Centres of Excellence initiative to M.W. and T.B.; the MSMT Navrat grant LK21307 to M.A.-J. S.P. and J.T. were supported by New England Biolabs. We thank R. White, D. Johnson, M. Frank-Kamenetskii, S. M. Mirkin, D. Gautheret, B. Tazon-Vega, C. Bonifer, C. Bock, M. T. Voso, J. J. Dunn (deceased) and R. A. M. Fouchier for helpful advice and reagents; I. Rigoutsos for providing the latest released pyknons database; all the members of the Tenen Laboratory; P. Tan and T. S. Ting from the Genome Institute of Singapore; R. Soong from the Cancer Science Institute Translational Interface; J. LaVecchio and G. Buruzula from the Harvard Stem Cell Institute/Joslin Diabetes Center flow cytometry facility; and F. Hyde from Epicentre-Illumina. This research is supported by the Singapore Ministry of Health{\textquoteright}s National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award (D.G.T.).",
year = "2013",
doi = "10.1038/nature12598",
language = "English (US)",
volume = "503",
pages = "371--376",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7476",
}