DNMT1-interacting RNAs block gene-specific DNA methylation

Annalisa Di Ruscio, Alexander K. Ebralidze, Touati Benoukraf, Giovanni Amabile, Loyal A. Goff, Jolyon Terragni, Maria Eugenia Figueroa, Lorena Lobo De Figueiredo Pontes, Meritxell Alberich-Jorda, Pu Zhang, Mengchu Wu, Francesco D’Alò, Ari Melnick, Giuseppe Leone, Konstantin K. Ebralidze, Sriharsa Pradhan, John L. Rinn and Daniel G. Tenen ()
Additional contact information
Annalisa Di Ruscio: Harvard Stem Cell Institute, Harvard Medical School
Alexander K. Ebralidze: Harvard Stem Cell Institute, Harvard Medical School
Touati Benoukraf: Cancer Science Institute, National University of Singapore, 117599, Singapore
Giovanni Amabile: Harvard Stem Cell Institute, Harvard Medical School
Loyal A. Goff: Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
Jolyon Terragni: New England Biolabs, 240 County Road
Maria Eugenia Figueroa: University of Michigan
Lorena Lobo De Figueiredo Pontes: Harvard Stem Cell Institute, Harvard Medical School
Meritxell Alberich-Jorda: Harvard Stem Cell Institute, Harvard Medical School
Pu Zhang: Harvard Stem Cell Institute, Harvard Medical School
Mengchu Wu: Cancer Science Institute, National University of Singapore, 117599, Singapore
Francesco D’Alò: Università Cattolica del Sacro Cuore, Institute of Hematology, L.go A. Gemelli 8, Rome 00168, Italy
Ari Melnick: Hematology-Oncology, C-620 Weill Cornell Medical College, 1300 York Avenue, New York, New York 10021, USA
Giuseppe Leone: Università Cattolica del Sacro Cuore, Institute of Hematology, L.go A. Gemelli 8, Rome 00168, Italy
Konstantin K. Ebralidze: Beth Israel Deaconess Medical Center
Sriharsa Pradhan: New England Biolabs, 240 County Road
John L. Rinn: Harvard Stem Cell Institute, Harvard Medical School
Daniel G. Tenen: Harvard Stem Cell Institute, Harvard Medical School

Nature, 2013, vol. 503, issue 7476, 371-376

Abstract: 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.

Date: 2013
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DOI: 10.1038/nature12598

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