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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Base Sequence
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CCAAT-Enhancer-Binding Proteins / genetics*
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Cell Line
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases / metabolism*
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DNA / genetics
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DNA / metabolism
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DNA Methylation / genetics*
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Gene Expression Profiling
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Gene Expression Regulation / genetics*
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Genome, Human / genetics
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Humans
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Untranslated / genetics
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RNA, Untranslated / metabolism*
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RNA-Binding Proteins / metabolism
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Substrate Specificity
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Transcription, Genetic / genetics
Substances
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CCAAT-Enhancer-Binding Proteins
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CEBPA protein, human
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RNA, Messenger
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RNA, Untranslated
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RNA-Binding Proteins
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DNA
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DNA (Cytosine-5-)-Methyltransferase 1
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DNA (Cytosine-5-)-Methyltransferases
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DNMT1 protein, human
Associated data
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GEO/GSE32153
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GEO/GSE32162
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GEO/GSE32168
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GEO/GSE32260
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GEO/GSE41279