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Series GSE72860 Query DataSets for GSE72860
Status Public on Sep 10, 2015
Title Binding of 14-3-3 reader proteins to phosphorylated DNMT1 facilitates aberrant DNA methylation and gene expression
Organism Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary 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.  
Overall design Examine of the DNA methylation and RNA expression profiles of stable NIH3T3 clones overexressing the 14-3-3ε homologue
Contributor(s) Guoqiang Z, Sriharsa P
Citation(s) 26553800
Submission date Sep 09, 2015
Last update date May 15, 2019
Contact name Guoqiang Zhang
Organization name New England Biolabs Inc
Street address 240 County Road
City Ipswich
State/province Massachusetts
ZIP/Postal code 01938
Country USA
Platforms (2)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (8)
GSM1873497 NIH3T3_RRBS_C2
GSM1873498 NIH3T3_RRBS_C3
GSM1873499 NIH3T3_RRBS_EP10
BioProject PRJNA295204
SRA SRP063522

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE72860_RNA-seq_log2fdc.txt.gz 859.3 Kb (ftp)(http) TXT
GSE72860_RRBS_CpG_methylation_call.txt.gz 61.8 Mb (ftp)(http) TXT
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