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Small RNA mediated DNA (cytosine-5) methyltransferase 1 inhibition leads to aberrant DNA methylation


ABSTRACT: Mammalian cells contain copious amounts of RNA including both coding and non-coding RNA (ncRNA). Generally the ncRNAs function to regulate gene expression at the transcriptional and post-transcriptional level. Among ncRNA, the long ncRNA and small ncRNA can affect histone modification, DNA methylation targeting and gene silencing. Here we show that endogenous DNA methyltransferase 1 (DNMT1) co-purifies with inhibitory ncRNAs. MicroRNAs (miRNAs) binds directly to DNMT1 with high affinity. The binding of miRNAs, such as miR-155, leads to inhibition of DNMT1 enzyme activity. Exogenous miR-155 in cells induces aberrant DNA methylation of the genome, resulting in hypomethylation of low to moderately methylated regions. And small shift of hypermethylation of previously hypomethylated region was also observed. Furthermore, hypomethylation led to activation of genes. Based on these observations, we propose that overexpression of specific miRNAs in human cancer may lead to aberrant DNA methylation and altered gene-expression.  Examine of the DNA methylation and mRNA profile of HCT 116 cells transfected by random 23-mer or miR-155 RNA

ORGANISM(S): Homo sapiens

SUBMITTER: Guoqiang Zhang 

PROVIDER: E-GEOD-68027 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Small RNA-mediated DNA (cytosine-5) methyltransferase 1 inhibition leads to aberrant DNA methylation.

Zhang Guoqiang G   Estève Pierre-Olivier PO   Chin Hang Gyeong HG   Terragni Jolyon J   Dai Nan N   Corrêa Ivan R IR   Pradhan Sriharsa S  

Nucleic acids research 20150518 12


Mammalian cells contain copious amounts of RNA including both coding and noncoding RNA (ncRNA). Generally the ncRNAs function to regulate gene expression at the transcriptional and post-transcriptional level. Among ncRNA, the long ncRNA and small ncRNA can affect histone modification, DNA methylation targeting and gene silencing. Here we show that endogenous DNA methyltransferase 1 (DNMT1) co-purifies with inhibitory ncRNAs. MicroRNAs (miRNAs) bind directly to DNMT1 with high affinity. The bindi  ...[more]

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