DNMT1-interacting RNAs block gene-specific DNA methylation

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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]}

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^[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

• Tipo de documento: Artigo Científico
• Fonte: Nature; v. 503, n. 7476, p. 371+, NOV 21 2013.
• Citações Web of Science: 249

Resumo

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)

• Processo FAPESP: 11/11822-6 - Caracterização do perfil de expressão gênica dos subtipos de leucemia mielóide aguda com alterações genéticas do C/EBPA
• Beneficiário: Lorena Lôbo de Figueiredo Pontes
• Modalidade de apoio: Bolsas no Exterior - Pesquisa