期刊
NATURE
卷 503, 期 7476, 页码 371-+出版社
NATURE PORTFOLIO
DOI: 10.1038/nature12598
关键词
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资金
- National Institutes of Health (NIH) [CA118316, CA66996, HL56745, T32 HL007917-11A1]
- Italian Foundation for Cancer Research (FIRC)
- Societa Italiana di Ematologia Sperimentale (SIES)
- FAMRI CIA [103063]
- Fondazione Roma
- American Italian Cancer Foundation Fellowship (AICF)
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2011/11822-6]
- National Research Foundation
- Singapore Ministry of Education under its Centres of Excellence initiative
- MSMT Navrat grant [LK21307]
- New England Biolabs
- Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award
- Associazione Italiana per la Ricerca sul Cancro Funding Source: Custom
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.
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