TitleDNMT1-interacting RNAs block gene-specific DNA methylation.
Publication TypeJournal Article
Year of Publication2013
AuthorsDi Ruscio, Annalisa, Ebralidze Alexander K., Benoukraf Touati, Amabile Giovanni, Goff Loyal A., Terragni Jolyon, Figueroa Maria Eugenia, Pontes Lorena Lobo De Fi, Alberich-Jorda Meritxell, Zhang Pu, Wu Mengchu, D'Alò Francesco, Melnick Ari, Leone Giuseppe, Ebralidze Konstantin K., Pradhan Sriharsa, Rinn John L., and Tenen Daniel G.
JournalNature
Volume503
Issue7476
Pagination371-6
Date Published2013 Nov 21
ISSN1476-4687
KeywordsBase Sequence, CCAAT-Enhancer-Binding Proteins, Cell Line, DNA, DNA (Cytosine-5-)-Methyltransferase 1, DNA (Cytosine-5-)-Methyltransferases, DNA Methylation, Gene Expression Profiling, Gene Expression Regulation, Genome, Human, Humans, RNA, Messenger, RNA, Untranslated, RNA-Binding Proteins, Substrate Specificity, Transcription, Genetic
Abstract

<p>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.</p>

DOI10.1038/nature12598
Alternate JournalNature
PubMed ID24107992
PubMed Central IDPMC3870304
Grant ListCA66996 / CA / NCI NIH HHS / United States
T32 HL007917-11A1 / HL / NHLBI NIH HHS / United States
R01 CA118316 / CA / NCI NIH HHS / United States
CA118316 / CA / NCI NIH HHS / United States
P01 CA066996 / CA / NCI NIH HHS / United States
R01 HL112719 / HL / NHLBI NIH HHS / United States
T32 HL007917 / HL / NHLBI NIH HHS / United States
HL56745 / HL / NHLBI NIH HHS / United States
R01 HL056745 / HL / NHLBI NIH HHS / United States