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Binding of 14-3-3 reader proteins to phosphorylated DNMT1 facilitates aberrant DNA methylation and gene expression

ABSTRACT: Mammalian DNA (cytosine-5) methyltransferase 1 (DNMT1) is essential for maintenance methylation. Phosphorylation of Ser143 (pSer143) stabilizes DNMT1 during DNA replication. Here, we show 14-3-3 is a reader protein of DNMT1pSer143. In mammalian cells 14-3-3 colocalizes and binds DNMT1pSer143 post-DNA replication. The level of DNMT1pSer143 increased with overexpression of 14-3-3 and decreased by its depletion. Binding of 14-3-3 proteins with DNMT1pSer143 resulted in inhibition of DNA methylation activity in vitro. In addition, overexpression of 14-3-3 in NIH3T3 cells led to decrease in DNMT1 specific activity and was rescued by transfection of DNMT1. Decrease in DNMT1 specific activity led to hypomethylation of the genome. Genes representing cell migration, mobility, proliferation and focal adhesion pathway were hypomethylated and overexpressed. Furthermore, 14-3-3 overexpression also resulted in enhanced cell invasion. Therefore, we suggest that 14-3-3 is a crucial reader of DNMT1pSer143 that regulates DNMT1 level, DNA methylation and altered gene expression that contributes to cell invasion. Examine of the DNA methylation and RNA expression profiles of stable NIH3T3 clones overexressing the 14-3-3ε homologue

ORGANISM(S): Mus musculus

SUBMITTER: Guoqiang Zhang

PROVIDER: E-GEOD-72860 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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