|
| 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 |
| E-mail(s) |
zhangg@neb.com
|
| 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)
|
|
| Relations |
| BioProject |
PRJNA295204 |
| SRA |
SRP063522 |
Less...
More...