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DNMT1-interacting RNAs block gene-specific DNA methylation

Author

Listed:
  • Annalisa Di Ruscio

    (Harvard Stem Cell Institute, Harvard Medical School
    Beth Israel Deaconess Medical Center
    Università Cattolica del Sacro Cuore, Institute of Hematology, L.go A. Gemelli 8, Rome 00168, Italy)

  • Alexander K. Ebralidze

    (Harvard Stem Cell Institute, Harvard Medical School
    Beth Israel Deaconess Medical Center)

  • Touati Benoukraf

    (Cancer Science Institute, National University of Singapore, 117599, Singapore)

  • Giovanni Amabile

    (Harvard Stem Cell Institute, Harvard Medical School
    Beth Israel Deaconess Medical Center)

  • Loyal A. Goff

    (Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
    Broad Institute of MIT and Harvard, 7 Cambridge Center
    Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, 32 Vassar Street, Cambridge, Massachusetts 02139, 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
    Beth Israel Deaconess Medical Center)

  • Meritxell Alberich-Jorda

    (Harvard Stem Cell Institute, Harvard Medical School
    Beth Israel Deaconess Medical Center
    Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, 142 20 Prague, Czech Republic)

  • 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
    Beth Israel Deaconess Medical Center
    Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA
    Broad Institute of MIT and Harvard, 7 Cambridge Center)

  • Daniel G. Tenen

    (Harvard Stem Cell Institute, Harvard Medical School
    Cancer Science Institute, National University of Singapore, 117599, Singapore)

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.

Suggested Citation

  • 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-Jor, 2013. "DNMT1-interacting RNAs block gene-specific DNA methylation," Nature, Nature, vol. 503(7476), pages 371-376, November.
    • Handle: RePEc:nat:nature:v:503:y:2013:i:7476:d:10.1038_nature12598
    DOI: 10.1038/nature12598
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