DNMT1-interacting RNAs block gene-specific DNA methylation

Author(s):Show less -

Di Ruscio, Annalisa ^{[1, 2]} ; Ebralidze, Alexander K. ^{[1, 2]} ; Benoukraf, Touati ^[3] ; Amabile, Giovanni ^{[1, 2]} ; Goff, Loyal A. ^{[4, 5, 6]} ; Terragni, Jolyon ^[7] ; Figueroa, Maria Eugenia ^[8] ; Pontes, Lorena Lobo De Figueiredo ^{[1, 2]} ; Alberich-Jorda, Meritxell ^{[1, 2, 9]} ; Zhang, Pu ^[1] ; Wu, Mengchu ^[3] ; D'Alo, Francesco ^[10] ; Melnick, Ari ^[11] ; Leone, Giuseppe ^[10] ; Ebralidze, Konstantin K. ^[2] ; Pradhan, Sriharsa ^[7] ; Rinn, John L. ^{[1, 2, 5, 6]} ; Tenen, Daniel G. ^{[1, 3]}

Affiliation:Show less -

^[1] Harvard Univ, Sch Med, Harvard Stem Cell Inst, Boston, MA 02115 - USA

^[2] Beth Israel Deaconess Med Ctr, Boston, MA 02115 - USA

^[3] Natl Univ Singapore, Canc Sci Inst, Singapore 117599 - Singapore

^[4] MIT, Comp Sci & Artificial Intelligence Lab, Cambridge, MA 02139 - USA

^[5] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 - USA

^[6] Broad Inst MIT & Harvard, Cambridge Ctr 7, Cambridge, MA 02142 - USA

^[7] New England Biolabs Inc, Ipswich, MA 01938 - USA

^[8] Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 - USA

^[9] Acad Sci Czech Republic, Inst Mol Genet, CR-14220 Prague - Czech Republic

^[10] Univ Cattolica Sacro Cuore, Inst Hematol, I-00168 Rome - Italy

^[11] C620 Weill Cornell Med Coll, Dept Med, New York, NY 10021 - USA

• Document type: Journal article
• Source: Nature; v. 503, n. 7476, p. 371+, NOV 21 2013.
• Web of Science Citations: 249

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. (AU)

• FAPESP's process: 11/11822-6 - Analysis of the gene expression profile of acute myeloid leukemia subtypes with C/EBPA genetic abnormalities
• Grantee: Lorena Lôbo de Figueiredo Pontes
• Support Opportunities: Scholarships abroad - Research